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1.  Developing an adherence support intervention for patients on antiretroviral therapy in the context of the recent IDU-driven HIV/AIDS epidemic in Estonia 
AIDS care  2013;25(7):863-873.
There is limited data on and experience with interventions for antiretroviral therapy (ART) adherence support for patients on ART in Eastern Europe. We sought to identify a feasible adherence support intervention for delivery amongst HIV-positive adults receiving care in Estonia, where the HIV/AIDS epidemic has been mainly concentrated among injection drug users. Our application of intervention mapping strategies used existing literature, formative research and multidisciplinary team input to produce a brief clinic-based intervention entitled the Situated Optimal Adherence Intervention Estonia (sOAI Estonia) which uses both Next-Step Counseling and Information-Motivation-Behavioral Skills Model approach to facilitate integration of ART into the context and demands of daily life. We present the intervention development process, the resulting sOAI Estonia approach, and describe a randomized controlled trial which is underway to evaluate the intervention (results due in spring 2013).
doi:10.1080/09540121.2013.764393
PMCID: PMC3651786  PMID: 23391132
ART; HAART; adherence; intervention
2.  Health and Human Rights Concerns of Drug Users in Detention in Guangxi Province, China 
PLoS Medicine  2008;5(12):e234.
Background
Although confinement in drug detoxification (“detox”) and re-education through labor (RTL) centers is the most common form of treatment for drug dependence in China, little has been published about the experience of drug users in such settings. We conducted an assessment of the impact of detention on drug users' access to HIV prevention and treatment services and consequent threats to fundamental human rights protections.
Methods and Findings
Chinese government HIV and anti-narcotics legislation and policy documents were reviewed, and in-depth and key informant interviews were conducted with 19 injection drug users (IDUs) and 20 government and nongovernmental organization officials in Nanning and Baise, Guangxi Province. Significant contradictions were found in HIV and antinarcotics policies, exemplified by the simultaneous expansion of community-based methadone maintenance therapy and the increasing number of drug users detained in detox and RTL center facilities. IDU study participants reported, on average, having used drugs for 14 y (range 8–23 y) and had been confined to detox four times (range one to eight times) and to RTL centers once (range zero to three times). IDUs expressed an intense fear of being recognized by the police and being detained, regardless of current drug use. Key informants and IDUs reported that routine HIV testing, without consent and without disclosure of the result, was the standard policy of detox and RTL center facilities, and that HIV-infected detainees were not routinely provided medical or drug dependency treatment, including antiretroviral therapy. IDUs received little or no information or means of HIV prevention, but reported numerous risk behaviors for HIV transmission while detained.
Conclusions
Legal and policy review, and interviews with recently detained IDUs and key informants in Guangxi Province, China, found evidence of anti-narcotics policies and practices that appear to violate human rights and imperil drug users' health.
Based on their review of Chinese government legislation and policy documents, and using interviews with recently detained injection drug users and officials in Guangxi Province, Elizabeth Cohen and Joseph Amon find evidence of antinarcotics policies and practices that may compromise the health and human rights of drug users.
Editors' Summary
Background.
Ever since the AIDS (acquired immunodeficiency syndrome) epidemic began, needle sharing by injection drug users (IDUs) has been a major transmission route for the human immunodeficiency virus (HIV), the blood-borne virus that causes AIDS. In China, for example, the AIDS epidemic began in earnest in 1989 when 146 HIV-positive IDUs were identified in Southwest Yunnan. By 1998, HIV infections had been reported throughout China, 60%–70% of which were in IDUs. These days, nearly half of new HIV infections in China are associated with injection drug use and 266,000 of the 700,000 HIV-positive people in China are drug users. Faced with these figures, the Chinese government has recently introduced measures to reduce HIV transmission among the estimated 3–4 million IDUs in China. These measures include increased provision of methadone maintenance treatment clinics and needle exchanges and the establishment of HIV prevention programs that target IDUs.
Why Was This Study Done?
Alongside these progressive public-health practices, China has extremely punitive anti-narcotics policies. IDUs are routinely confined without legal review in drug detoxification centers or sent to re-education through labor (RTL) centers, sometimes for many years. In 2005, these centers housed more than 350,000 drug users yet little is known about the conditions in these centers or how the Chinese anti-narcotic policy affects human rights or access to HIV prevention and treatment services. In this study, the researchers investigated these issues by interviewing IDUs and “key informants” (government officials and members of nongovernmental organizations [NGOs] who provide services to IDUs) about their experiences of detoxification centers and RTL centers in two cities in Guangxi Province, China.
What Did the Researchers Do and Find?
The researchers recruited 19 IDUs who had been recently confined in a detoxification center or RTL center and 20 key informants (including a doctor at a detoxification center and a former RTL center guard). In the interviews the researchers used a semi-structured questionnaire to ask the participants about their experiences of detoxification centers and RTL centers. All the IDUs reported that they were repeatedly tested for HIV while in detention but never given their test results even when they asked for them. Key informants confirmed that repeated HIV testing without result disclosure is the current policy in detoxification centers and RTL centers. All the IDUs expressed concerns about inadequate access to health care in detention. In particular, most of the IDUs who were taking antiretroviral drugs before detention were unable to continue their treatment during detention, although two received antiretroviral drugs by negotiating with their guards. The IDUs and key informants also both noted that very little information or means of HIV prevention was provided in the detoxification centers and RTL centers and that HIV-related risk behaviors, including injection drug use and unsafe sex, occurred in both types of center. Finally, the IDUs reported that their fear of being recognized by the police and detained even if not taking drugs prevented them from seeking HIV tests, HIV treatment, and help for their drug addiction.
What Do These Findings Mean?
This study has several limitations in addition to its small size. For example, because the IDUs were self selected—they responded to posters asking if they would be interviewed—their views may not be representative of all IDUs. Similarly, the key informants who were interviewed might have had different opinions from those who chose not to participate. Furthermore, the results reported here cannot be generalized to other areas of China. Nevertheless, the consistent experiences reported by the IDUs and confirmed by the key informants suggest that China's anti-narcotic policies and practices violate the human rights of IDUs and put their health in danger by making it hard for them to access HIV prevention and treatment or adequate treatment for their drug addiction. This situation, if not remedied, is likely to jeopardize China's attempts to control its HIV epidemic.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050234.
This study is further discussed in a PLoS Medicine Perspective by Steve Koester
Avert, an international AIDS charity, provides information on all aspects of HIV/AIDS, including HIV and AIDS in China and HIV prevention, harm reduction, and injecting drug use
The UNAIDS 2008 Country Progress Report provides up-to-date details about the AIDS situation in China
HIVInSite provides links to more information about HIV/AIDS in China.
Human Rights Watch works on health and human rights and human rights developments in China
The US National Institute on Drug Abuse provides a booklet entitled Principles of Drug Addiction Treatment: A Research Based Guide (in English and Spanish)
UN Office on Drugs and Crime has information on HIV/AIDS in prisons
doi:10.1371/journal.pmed.0050234
PMCID: PMC2596857  PMID: 19071954
3.  Changes in HIV Incidence among People Who Inject Drugs in Taiwan following Introduction of a Harm Reduction Program: A Study of Two Cohorts 
PLoS Medicine  2014;11(4):e1001625.
Kenrad Nelson and colleagues report on the association between HIV incidence and exposure to a national harm-reduction program among people who inject drugs in Taiwan.
Please see later in the article for the Editors' Summary
Background
Harm reduction strategies for combating HIV epidemics among people who inject drugs (PWID) have been implemented in several countries. However, large-scale studies using sensitive measurements of HIV incidence and intervention exposures in defined cohorts are rare. The aim of this study was to determine the association between harm reduction programs and HIV incidence among PWID.
Methods and Findings
The study included two populations. For 3,851 PWID who entered prison between 2004 and 2010 and tested HIV positive upon incarceration, we tested their sera using a BED HIV-1 capture enzyme immunoassay to estimate HIV incidence. Also, we enrolled in a prospective study a cohort of 4,357 individuals who were released from prison via an amnesty on July 16, 2007. We followed them with interviews at intervals of 6–12 mo and by linking several databases. A total of 2,473 participants who were HIV negative in January 2006 had interviews between then and 2010 to evaluate the association between use of harm reduction programs and HIV incidence. We used survival methods with attendance at methadone clinics as a time-varying covariate to measure the association with HIV incidence. We used a Poisson regression model and calculated the HIV incidence rate to evaluate the association between needle/syringe program use and HIV incidence. Among the population of PWID who were imprisoned, the implementation of comprehensive harm reduction programs and a lower mean community HIV viral load were associated with a reduced HIV incidence among PWID. The HIV incidence in this population of PWID decreased from 18.2% in 2005 to 0.3% in 2010. In an individual-level analysis of the amnesty cohort, attendance at methadone clinics was associated with a significantly lower HIV incidence (adjusted hazard ratio: 0.20, 95% CI: 0.06–0.67), and frequent users of needle/syringe program services had lower HIV incidence (0% in high NSP users, 0.5% in non NSP users). In addition, no HIV seroconversions were detected among prison inmates.
Conclusions
Although our data are affected by participation bias, they strongly suggest that comprehensive harm- reduction services and free treatment were associated with reversal of a rapidly emerging epidemic of HIV among PWID.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 35 million people worldwide are currently infected with HIV, the virus that causes AIDS, and about 2.3 million people become newly infected every year. HIV is mainly transmitted through unprotected sex with an infected partner. However, people who inject drugs (PWID) have a particularly high risk of HIV infection because blood transfer through needle and syringe sharing can transmit the virus. It is estimated that 5%–10% of all people living with HIV are PWID. Indeed, in some regions of the world the primary route of HIV transmission is through shared drug injection equipment and the prevalence (the proportion of a population that has a specific disease) of HIV infection among PWID is very high. In Asia, for example, more than a quarter of PWID are HIV positive. Because the high prevalence of HIV among PWID poses a global health challenge, bodies such as the Joint United Nations Programme on HIV/AIDS endorse harm reduction strategies to prevent risky injection behaviors among PWID. These strategies include the provision of clean needles and syringes, opioid substitution therapy such as methadone maintenance treatment, and antiretroviral treatment for HIV-positive PWID.
Why Was This Study Done?
Although harm reduction strategies for combating HIV epidemics among PWID have been implemented in several countries, few large-scale studies have examined the association between HIV incidence (the proportion of new cases of HIV in a population per year) and exposure to harm reduction programs among PWID. In this cohort study (an investigation that determines the characteristics of a group of people and then follows them over time), the researchers determine the association between harm reduction programs and HIV incidence among PWID in Taiwan. HIV infections used to be rare among the 60,000 PWID living in Taiwan, but after the introduction of a new HIV strain into the country in 2003, an HIV epidemic spread rapidly. In response, the Taiwanese government introduced a pilot program of harm reduction that included the provision of clean needles and syringes and health education in July 2005. The program was expanded to include methadone maintenance treatment in early 2006 and implemented nationwide in June 2006.
What Did the Researchers Do and Find?
The researchers enrolled two study populations. The first cohort comprised 3,851 PWID who were incarcerated for illicit drug use between 2004 and 2010 and who tested positive for HIV upon admission into prison. By using the BED assay, which indicates whether an HIV infection is recent, the researchers were able to determine the HIV incidence among the prisoners. In 2004, the estimated HIV incidence among prisoners with a history of drug injection was 6.44%. The incidence peaked in 2005 at 18.2%, but fell to 0.3% in 2010.
The second study population comprised 2,473 individuals who were HIV negative on January 1, 2006, and who had been incarcerated for drug use crimes but were released on July 16, 2007, during an amnesty. The researchers regularly interviewed these participants between their release and 2010 about their use of harm reduction interventions, and obtained other data about them (for example, diagnosis of HIV infection) from official databases. Analysis of all these data indicated that, in this cohort, attendance at methadone maintenance treatment clinics and frequent use of needle and syringe services were both associated with a significantly lower HIV incidence.
What Do These Findings Mean?
These findings suggest that the introduction of a comprehensive harm reduction program in Taiwan was associated with a significant reduction in the HIV incidence rate among PWID. These findings must be interpreted with caution, however. First, because the participants in the study were selected from PWID with histories of incarceration, the findings may not be representative of all PWID in Taiwan or of PWID in other countries. Second, PWID who chose to use needle and syringe services or methadone maintenance treatment clinics might have shared other unknown characteristics that affected their risk of HIV infection. Finally, some of the reduction in HIV incidence seen during the study is likely to be associated with the availability of free treatment, which has been offered to all HIV-positive individuals in Taiwan since 1997. Despite these limitations, these findings suggest that countries with a high prevalence and incidence of HIV among PWID should provide comprehensive harm reduction services to their populations to reduce risky drug injection behaviors.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001625.
Information is available from the US National Institute of Allergy and Infectious diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on injecting drug users and HIV/AIDS and on harm reduction and HIV prevention (in English and Spanish)
The US National Institute on Drug Abuse also provides information about drug abuse and HIV/AIDS (in English and Spanish)
The 2013 UNAIDS World AIDS Day report provides up-to-date information about the AIDS epidemic and efforts to halt it
Personal stories about living with HIV/AIDS are available through Avert, Nam/aidsmap, and Healthtalkonline
doi:10.1371/journal.pmed.1001625
PMCID: PMC3979649  PMID: 24714449
4.  Effectiveness and Cost Effectiveness of Expanding Harm Reduction and Antiretroviral Therapy in a Mixed HIV Epidemic: A Modeling Analysis for Ukraine 
PLoS Medicine  2011;8(3):e1000423.
A cost-effectiveness study by Sabina Alistar and colleagues evaluates the effectiveness and cost effectiveness of different levels of investment in methadone, ART, or both, in the mixed HIV epidemic in Ukraine.
Background
Injection drug use (IDU) and heterosexual virus transmission both contribute to the growing mixed HIV epidemics in Eastern Europe and Central Asia. In Ukraine—chosen in this study as a representative country—IDU-related risk behaviors cause half of new infections, but few injection drug users (IDUs) receive methadone substitution therapy. Only 10% of eligible individuals receive antiretroviral therapy (ART). The appropriate resource allocation between these programs has not been studied. We estimated the effectiveness and cost-effectiveness of strategies for expanding methadone substitution therapy programs and ART in mixed HIV epidemics, using Ukraine as a case study.
Methods and Findings
We developed a dynamic compartmental model of the HIV epidemic in a population of non-IDUs, IDUs using opiates, and IDUs on methadone substitution therapy, stratified by HIV status, and populated it with data from the Ukraine. We considered interventions expanding methadone substitution therapy, increasing access to ART, or both. We measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, infections averted, and incremental cost-effectiveness. Without incremental interventions, HIV prevalence reached 67.2% (IDUs) and 0.88% (non-IDUs) after 20 years. Offering methadone substitution therapy to 25% of IDUs reduced prevalence most effectively (to 53.1% IDUs, 0.80% non-IDUs), and was most cost-effective, averting 4,700 infections and adding 76,000 QALYs compared with no intervention at US$530/QALY gained. Expanding both ART (80% coverage of those eligible for ART according to WHO criteria) and methadone substitution therapy (25% coverage) was the next most cost-effective strategy, adding 105,000 QALYs at US$1,120/QALY gained versus the methadone substitution therapy-only strategy and averting 8,300 infections versus no intervention. Expanding only ART (80% coverage) added 38,000 QALYs at US$2,240/QALY gained versus the methadone substitution therapy-only strategy, and averted 4,080 infections versus no intervention. Offering ART to 80% of non-IDUs eligible for treatment by WHO criteria, but only 10% of IDUs, averted only 1,800 infections versus no intervention and was not cost effective.
Conclusions
Methadone substitution therapy is a highly cost-effective option for the growing mixed HIV epidemic in Ukraine. A strategy that expands both methadone substitution therapy and ART to high levels is the most effective intervention, and is very cost effective by WHO criteria. When expanding ART, access to methadone substitution therapy provides additional benefit in infections averted. Our findings are potentially relevant to other settings with mixed HIV epidemics.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
HIV epidemics in Eastern Europe and Central Asia are mainly driven by increasing use of injection drugs combined with heterosexual transmission. In the Ukraine, in 2007, there were 82,000 officially registered people living with HIV—three times the number registered in 1999—and an estimated 395,000 HIV infected adults. The epidemic in Ukraine, like other countries in the region, is concentrated in at-risk populations, particularly people who inject drugs: in 2007, an estimated 390,000 Ukrainians were injecting drugs, an increase in drug use over the previous decade, not only in Ukraine, but in other former USSR states, owing to the easy availability of precursors for injection drugs in a climate of economic collapse.
The common practices of people who inject drugs in Ukraine and in other countries in the region, such as social injecting, syringe sharing, and using common containers, increase the risk of transmitting HIV. Public health interventions such as needle exchange can limit these risk factors and have been gradually implemented in these countries. In 2007, Ukraine approved the use of methadone substitution therapy and the current target is for 11,000 people who inject drugs to be enrolled in substitution therapy by 2011. Furthermore, since treatment for HIV-infected individuals is also necessary, national HIV control plans included a target of 90% antiretroviral therapy (ART) coverage by 2010 but in 2007 less than 10% of the 91,000 eligible people received treatment. Although the number of people who inject drugs and who receive ART is unknown, physicians are often reluctant to treat people who inject drugs using ART owing to alleged poor compliance.
Why Was This Study Done?
As resources for HIV interventions in the region are limited, it is important to investigate the appropriate balance between investments in methadone substitution therapy and ART in order to maximize benefits to public health. Several studies have analyzed the cost effectiveness of methadone substitution therapy in similar settings but have not considered tradeoffs between ART and methadone substitution therapy. Therefore, to provide insights into the appropriate public health investment in methadone substitution therapy and ART in Ukraine, the researchers evaluated the public health effectiveness and cost effectiveness of different strategies for scaling up methadone substitution therapy and/or expanding ART.
What Did the Researchers Do and Find?
The researchers developed a model to accommodate different population groups: people who inject drugs on substitution therapy with methadone; people who inject opiates and do not take any substitution therapy; and people who do not inject any drugs, hence do not need substitution therapy. The researchers inputted Ukraine country-level data into this model and used current HIV trends in Ukraine to make rational assumptions on possible future trends and scenarios. They considered scenarios expanding methadone substitution therapy availability, increasing acces to ART, or both. Then, the researchers measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, infections averted, and incremental cost effectiveness for the different scenarios. They found that after 20 years, HIV prevalence reached 67.2% in people who inject drugs and 0.88% in people who do not inject drugs without further interventions. Offering methadone substitution therapy to 25% of people who inject drugs was the most effective strategy in reducing prevalence of HIV and was also the most cost effective, averting 4,700 infections and adding 75,700 QALYs versus the status quo at $530/QALY gained. Expanding both methadone substitution therapy and ART was also a highly cost effective option, adding 105,000 QALYs at US$1,120/QALY gained versus the methadone substitution therapy-only strategy. Offering ART to 80% of eligible people who did not inject drugs, and 10% of people who injected drugs averted only 1,800 infections, and added 76,400 QALYs at $1,330/QALY gained.
What Do These Findings Mean?
The results show that methadone substitution-focused therapeutic scenarios are the most cost effective, and that benefits increase with the scale of the project, even among people who do not inject drugs. This makes a methadone substitution strategy a highly cost-effective option for addressing the growing HIV epidemic in Ukraine. Therefore, if it is not feasible to invest in large-scale methadone substitution programs for any reason, political circumstances for example, providing as much methadone substitution as is acceptable is still desirable. While substitution therapy appears to avert the most HIV infections, expanded ART provides the largest total increase in QALYs. Thus, methadone substitution therapy and ART offer complementary benefits. Because the HIV epidemic in Ukraine is representative of the HIV epidemic in Eastern Europe and Central Asia, the cost-effective strategies that the researchers have identified may help inform all decision makers faced with a mixed HIV epidemic.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000423.
Alliance provides information on its work supporting community action on AIDS in Ukraine
USAID provides an HIV/AIDS Health Profile for Ukraine
UNICEF provides information about its activities to help Ukraine fight rising HIV/AIDS infection rates
International Harm Reduction Association provides information about the status of harm reduction interventions such as methadone substitution therapy around the world
doi:10.1371/journal.pmed.1000423
PMCID: PMC3046988  PMID: 21390264
5.  HIV among People Who Inject Drugs in the Middle East and North Africa: Systematic Review and Data Synthesis 
PLoS Medicine  2014;11(6):e1001663.
Laith Abu-Raddad and colleagues assess the current state of knowledge of the HIV epidemic among people who inject drugs in the Middle East and North Africa.
Please see later in the article for the Editors' Summary
Background
It is perceived that little is known about the epidemiology of HIV infection among people who inject drugs (PWID) in the Middle East and North Africa (MENA). The primary objective of this study was to assess the status of the HIV epidemic among PWID in MENA by describing HIV prevalence and incidence. Secondary objectives were to describe the risk behavior environment and the HIV epidemic potential among PWID, and to estimate the prevalence of injecting drug use in MENA.
Methods and Findings
This was a systematic review following the PRISMA guidelines and covering 23 MENA countries. PubMed, Embase, regional and international databases, as well as country-level reports were searched up to December 16, 2013. Primary studies reporting (1) the prevalence/incidence of HIV, other sexually transmitted infections, or hepatitis C virus (HCV) among PWIDs; or (2) the prevalence of injecting or sexual risk behaviors, or HIV knowledge among PWID; or (3) the number/proportion of PWID in MENA countries, were eligible for inclusion. The quality, quantity, and geographic coverage of the data were assessed at country level. Risk of bias in predefined quality domains was described to assess the quality of available HIV prevalence measures. After multiple level screening, 192 eligible reports were included in the review. There were 197 HIV prevalence measures on a total of 58,241 PWID extracted from reports, and an additional 226 HIV prevalence measures extracted from the databases.
We estimated that there are 626,000 PWID in MENA (range: 335,000–1,635,000, prevalence of 0.24 per 100 adults). We found evidence of HIV epidemics among PWID in at least one-third of MENA countries, most of which are emerging concentrated epidemics and with HIV prevalence overall in the range of 10%–15%. Some of the epidemics have however already reached considerable levels including some of the highest HIV prevalence among PWID globally (87.1% in Tripoli, Libya). The relatively high prevalence of sharing needles/syringes (18%–28% in the last injection), the low levels of condom use (20%–54% ever condom use), the high levels of having sex with sex workers and of men having sex with men (15%–30% and 2%–10% in the last year, respectively), and of selling sex (5%–29% in the last year), indicate a high injecting and sexual risk environment. The prevalence of HCV (31%–64%) and of sexually transmitted infections suggest high levels of risk behavior indicative of the potential for more and larger HIV epidemics.
Conclusions
Our study identified a large volume of HIV-related biological and behavioral data among PWID in the MENA region. The coverage and quality of the data varied between countries. There is robust evidence for HIV epidemics among PWID in multiple countries, most of which have emerged within the last decade and continue to grow. The lack of sufficient evidence in some MENA countries does not preclude the possibility of hidden epidemics among PWID in these settings. With the HIV epidemic among PWID in overall a relatively early phase, there is a window of opportunity for prevention that should not be missed through the provision of comprehensive programs, including scale-up of harm reduction services and expansion of surveillance systems.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 35 million people worldwide are currently infected with HIV, the virus that causes AIDS, and around 2.3 million people become newly infected every year. HIV is mainly transmitted through unprotected sex with an infected partner. However, people who inject drugs (PWID) have a particularly high risk of HIV infection because blood transfer through needle and syringe sharing can transmit the virus. Worldwide, 5%–10% of all HIV-positive people are PWID but in some regions of the world the fraction of all HIV-positive people that are PWID is even higher. To meet the global health challenge of the high HIV prevalence (the proportion of a population that has a specific disease) among PWID, the Joint United Nations Programme on HIV/AIDS (UNAIDS) and other international bodies endorse harm reduction strategies to prevent risky injection behaviors among PWID. These strategies include education and the provision of clean needles, syringes, and opioid substitution therapy.
Why Was This Study Done?
To maximize the effect of these harm-reduction strategies in specific regions, it is important to understand the status of the HIV epidemic among PWID. Although surveillance systems provide the information on HIV infection needed to track the progress of HIV epidemics among PWID in many regions, little is known about the HIV epidemic among PWID in the Middle East and North Africa (MENA, a geographical region that encompasses countries that share historical, socio-cultural, linguistic, and religious characteristics). Several factors contribute to the likelihood of individuals injecting drugs in MENA. For example, Afghanistan (a MENA country) produces most of the world's supply of heroin, which is largely trafficked through Iran and Pakistan (also MENA countries). In this systematic review and data synthesis, the researchers use predefined criteria to identify all the published and unpublished data on HIV prevalence and incidence (the number of new cases of a disease in a population in a given time) among PWID in MENA and combine (synthesize) these data to assess the status of the HIV epidemic in this key population for HIV transmission in MENA.
What Did the Researchers Do and Find?
The researchers identified 192 reports that reported the prevalence/incidence of HIV, other sexually transmitted infections and infection with hepatitis C virus (HCV, another virus transmitted through drug injection) among PWID, the prevalence of injecting or sexual risk behaviors among PWID, or the number/proportion of PWID in MENA. From these data, the researchers estimated that there are about 600,000 PWID in MENA (a prevalence of 0.24 per 100 adults, which is comparable with figures from other regions). The data provided evidence for HIV epidemics among PWID in at least a third of MENA countries, mainly emerging concentrated epidemics (epidemics that are still growing but in which HIV infection and transmission are already considerable). HIV prevalence among PWID in MENA varied considerably, reaching an extremely high prevalence of 87.1% in Tripoli, Libya. The data also revealed a high injecting and sexual risk environment among PWID in MENA (for example, on average, about a quarter of PWID shared a needle or syringe in their most recent injection and only a third reported ever using condoms) that, together with a high prevalence of HCV and sexually transmitted infections among PWID, indicates the potential for more and larger HIV epidemics.
What Do These Findings Mean?
These findings indicate that substantial amounts of HIV-related data have been collected from PWID in MENA but that the coverage and quality of these data vary widely between countries. They provide robust evidence for growing HIV epidemics, most of which have emerged within the past decade, among PWID in several MENA countries, but do not preclude the possibility of hidden epidemics among PWID in additional MENA countries. Overall, these findings suggest that the HIV epidemic among PWID in MENA is at a relatively early stage. This window of opportunity to control the emerging epidemics should not be missed, warn the researchers. HIV surveillance among PWID in MENA must be expanded to detect and monitor emerging and growing HIV epidemics, they suggest, and to inform effective HIV policy and programming. Improvements in HIV prevention and treatment among PWID in MENA are essential, they conclude, to confront the growing HIV problem in this population and, to prevent the onward transmission of HIV from PWID to other population groups.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001663.
A 2010 report produced by the World Bank, UNAIDS, and WHO provides information on the status of the HIV epidemic in the Middle East and North Africa; the UNAIDS Middle East and North Africa Regional Report on AIDS 2011 provides further information
The 2013 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it
The Middle East and North Africa Harm Reduction Association (MENAHRA) provides information about harm reduction efforts, services, and programs in the Middle East and North Africa; Harm Reduction International provides information about harm reduction concepts, strategies, programs, and publications globally
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on people who inject drugs and HIV/AIDS and on harm reduction and HIV prevention (in English and Spanish)
The US National Institute on Drug Abuse also provides information about drug abuse and HIV/AIDS (in English and Spanish)
Personal stories about living with HIV/AIDS are available through Avert, Nam/aidsmap, and Healthtalkonline
doi:10.1371/journal.pmed.1001663
PMCID: PMC4061009  PMID: 24937136
6.  Enhanced tuberculosis case detection among substitution treatment patients: a randomized controlled trial 
BMC Research Notes  2011;4:192.
Background
Historically, HIV, TB (tuberculosis) and illegal drug treatment services in Estonia have been developed as vertical structures. Related health care services are often provided by different health care institutions and in different locations. This may present obstacles for vulnerable groups, such as injecting drug users (IDU), to access the needed services. We conducted a small scale randomized controlled trial to evaluate a case management intervention aimed at increasing TB screening and treatment entry among IDUs referred from a methadone drug treatment program in Jõhvi, North-Eastern Estonia.
Findings
Of the 189 potential subjects, 112 (59%) participated. HIV prevalence was 86% (n = 96) and 7.4% (n = 8) of participants were interferon gamma release assay (IGRA) positive (6.5% were both HIV and IGRA-positive, n = 7). Overall, 44% of participants (n = 49) attended TB clinic, 17 (30%) from control group and 32 (57%) from case management group (p = 0.004). None of the participants were diagnosed with TB. In a multivariate model, those randomized to case management group were more likely to access TB screening services.
Conclusions
These findings demonstrate the urgent need for scaling up TB screening among IDUs and the value of more active approach in referring substitution treatment patients to TB services.
Trial registration
ClinicalTrials.gov: NCT01290081
doi:10.1186/1756-0500-4-192
PMCID: PMC3138461  PMID: 21676222
7.  Towards Universal Voluntary HIV Testing and Counselling: A Systematic Review and Meta-Analysis of Community-Based Approaches 
PLoS Medicine  2013;10(8):e1001496.
In a systematic review and meta-analysis, Amitabh Suthar and colleagues describe the evidence base for different HIV testing and counseling services provided outside of health facilities.
Please see later in the article for the Editors' Summary
Background
Effective national and global HIV responses require a significant expansion of HIV testing and counselling (HTC) to expand access to prevention and care. Facility-based HTC, while essential, is unlikely to meet national and global targets on its own. This article systematically reviews the evidence for community-based HTC.
Methods and Findings
PubMed was searched on 4 March 2013, clinical trial registries were searched on 3 September 2012, and Embase and the World Health Organization Global Index Medicus were searched on 10 April 2012 for studies including community-based HTC (i.e., HTC outside of health facilities). Randomised controlled trials, and observational studies were eligible if they included a community-based testing approach and reported one or more of the following outcomes: uptake, proportion receiving their first HIV test, CD4 value at diagnosis, linkage to care, HIV positivity rate, HTC coverage, HIV incidence, or cost per person tested (outcomes are defined fully in the text). The following community-based HTC approaches were reviewed: (1) door-to-door testing (systematically offering HTC to homes in a catchment area), (2) mobile testing for the general population (offering HTC via a mobile HTC service), (3) index testing (offering HTC to household members of people with HIV and persons who may have been exposed to HIV), (4) mobile testing for men who have sex with men, (5) mobile testing for people who inject drugs, (6) mobile testing for female sex workers, (7) mobile testing for adolescents, (8) self-testing, (9) workplace HTC, (10) church-based HTC, and (11) school-based HTC. The Newcastle-Ottawa Quality Assessment Scale and the Cochrane Collaboration's “risk of bias” tool were used to assess the risk of bias in studies with a comparator arm included in pooled estimates.
 117 studies, including 864,651 participants completing HTC, met the inclusion criteria. The percentage of people offered community-based HTC who accepted HTC was as follows: index testing, 88% of 12,052 participants; self-testing, 87% of 1,839 participants; mobile testing, 87% of 79,475 participants; door-to-door testing, 80% of 555,267 participants; workplace testing, 67% of 62,406 participants; and school-based testing, 62% of 2,593 participants. Mobile HTC uptake among key populations (men who have sex with men, people who inject drugs, female sex workers, and adolescents) ranged from 9% to 100% (among 41,110 participants across studies), with heterogeneity related to how testing was offered. Community-based approaches increased HTC uptake (relative risk [RR] 10.65, 95% confidence interval [CI] 6.27–18.08), the proportion of first-time testers (RR 1.23, 95% CI 1.06–1.42), and the proportion of participants with CD4 counts above 350 cells/µl (RR 1.42, 95% CI 1.16–1.74), and obtained a lower positivity rate (RR 0.59, 95% CI 0.37–0.96), relative to facility-based approaches. 80% (95% CI 75%–85%) of 5,832 community-based HTC participants obtained a CD4 measurement following HIV diagnosis, and 73% (95% CI 61%–85%) of 527 community-based HTC participants initiated antiretroviral therapy following a CD4 measurement indicating eligibility. The data on linking participants without HIV to prevention services were limited. In low- and middle-income countries, the cost per person tested ranged from US$2–US$126. At the population level, community-based HTC increased HTC coverage (RR 7.07, 95% CI 3.52–14.22) and reduced HIV incidence (RR 0.86, 95% CI 0.73–1.02), although the incidence reduction lacked statistical significance. No studies reported any harm arising as a result of having been tested.
Conclusions
Community-based HTC achieved high rates of HTC uptake, reached people with high CD4 counts, and linked people to care. It also obtained a lower HIV positivity rate relative to facility-based approaches. Further research is needed to further improve acceptability of community-based HTC for key populations. HIV programmes should offer community-based HTC linked to prevention and care, in addition to facility-based HTC, to support increased access to HIV prevention, care, and treatment.
Review Registration
International Prospective Register of Systematic Reviews CRD42012002554
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Three decades into the AIDS epidemic, about 34 million people (most living in resource-limited countries) are infected with HIV, the virus that causes AIDS. Every year another 2.2 million people become infected with HIV, usually through unprotected sex with an infected partner, and about 1.7 million people die. Infection with HIV, which gradually destroys the CD4 lymphocytes and other immune system cells that provide protection from life-threatening infections, is usually diagnosed by looking for antibodies to HIV in the blood or saliva. Disease progression is subsequently monitored in HIV-positive individuals by counting the CD4 cells in their blood. Initiation of antiretroviral drug therapy—a combination of drugs that keeps HIV replication in check but that does not cure the infection—is recommended when an individual's CD4 count falls below 500 cells/µl of blood or when he or she develops signs of severe or advanced disease, such as unusual infections.
Why Was This Study Done?
As part of intensified efforts to eliminate HIV/AIDS, United Nations member states recently set several HIV-related targets to be achieved by 2015, including reduced transmission of HIV and increased delivery of antiretroviral therapy. These targets can only be achieved if there is a large expansion in HIV testing and counseling (HTC) and increased access to HIV prevention and care services. The World Health Organization currently recommends that everyone attending a healthcare facility in regions where there is a generalized HIV epidemic (defined as when 1% or more of the general population is HIV-positive) should be offered HTC. However, many people rarely visit healthcare facilities, and others refuse “facility-based” HTC because they fear stigmatization and discrimination. Thus, facility-based HTC alone is unlikely to be sufficient to enable national and global HIV targets to be reached. In this systematic review and meta-analysis, the researchers evaluate the performance of community-based HTC approaches such as index testing (offering HTC to the sexual and injecting partners and household members of people with HIV), mobile testing (offering HTC through a service that visits shopping centers and other public facilities), and door-to-door testing (systematically offering HTC to homes in a catchment area). A systematic review uses predefined criteria to identify all the research on a given topic; meta-analysis combines the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 117 studies (most undertaken in Africa and North America) involving 864,651 participants that evaluated community-based HTC approaches. Among these studies, the percentage of people offered community-based HTC who accepted it (HTC uptake) was 88% for index testing, 87% for self-testing, 80% for door-to-door testing, 67% for workplace testing, and 62% for school-based testing. Compared to facility-based approaches, community-based approaches increased the chances of an individual's CD4 count being above 350 cells/µl at diagnosis (an important observation because early diagnosis improves subsequent outcomes) but had a lower positivity rate, possibly because people with symptoms of HIV are more likely to visit healthcare facilities than healthy individuals. Importantly, 80% of participants in the community-based HTC studies had their CD4 count measured after HIV diagnosis, and 73% of the participants initiated antiretroviral therapy after their CD4 count fell below national eligibility criteria; both these observations suggest that community-based HTC successfully linked people to care. Finally, offering community-based HTC approaches in addition to facility-based approaches increased HTC coverage seven-fold at the population level.
What Do These Findings Mean?
These findings show that community-based HTC can achieve high HTC uptake rates and can reach HIV-positive individuals earlier, when they still have high CD4 counts. Importantly, they also suggest that the level of linkage to care of community-based HTC is similar to that of facility-based HTC. Although the lower positivity rate of community-based HTC approaches means that more people need to be tested with these approaches than with facility-based HTC to identify the same number of HIV-positive individuals, this downside of community-based HTC is likely to be offset by the earlier identification of HIV-positive individuals, which should improve life expectancy and reduce HIV transmission at the population level. Although further studies are needed to evaluate community-based HTC in other regions of the world, these findings suggest that offering community-based HTC in HIV programs in addition to facility-based testing should support the increased access to HIV prevention and care that is required for the intensification of HIV/AIDS elimination efforts.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001496.
The World Health Organization provides information on all aspects of HIV/AIDS, including information on counseling and testing (in several languages)
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on the global HIV/AIDS epidemic, on HIV testing, and on HIV transmission and testing (in English and Spanish)
The UK National Health Service Choices website provides information (including personal stories) about HIV and AIDS
The World AIDS Day Report 2012 provides up-to-date information about the AIDS epidemic and efforts to halt it
Patient stories about living with HIV/AIDS are available through Avert; the nonprofit website Healthtalkonline also provides personal stories about living with HIV, including stories about getting a diagnosis
doi:10.1371/journal.pmed.1001496
PMCID: PMC3742447  PMID: 23966838
8.  Comparison of injecting drug users who obtain syringes from pharmacies and syringe exchange programs in Tallinn, Estonia 
Background
Both syringe exchange programs (SEPs) and pharmacy sales of syringes are available in Estonia, though the current high incidence and high prevalence of HIV among injection drug users (IDUs) in Tallinn, Estonia requires large-scale implementation of additional harm reduction programs as a matter of great urgency. The aims of this report were to compare risk behavior and HIV infection and to assess the prevention needs among IDUs who primarily use pharmacies as their source of sterile syringes with IDUs who primarily use SEPs in Tallinn.
Methods
A cross-sectional study using respondent-driven sampling was used to recruit 350 IDUs for an interviewer-administered survey and HIV testing. IDUs were categorized into two groups based on their self-reported main source for syringes within the last six months. Odds ratios with 95% CI were used to compare characteristics and risk factors between the groups.
Results
The main sources of sterile needles for injection drug users were SEP/SEP outreach (59%) and pharmacies (41%). There were no differences in age, age at injection drug use initiation, the main drug used or experiencing overdoses. Those IDUs using pharmacies as a main source of sterile needles had lower odds for being infected with either HIV (AOR 0.54 95% CI 0.33–0.87) or HCV (AOR 0.10 95% CI 0.02–0.50), had close to twice the odds of reporting more than one sexual partner within the previous 12 months (AOR 1.88 95% CI 1.17–3.04) and engaging in casual sexual relationships (AOR 2.09 95% CI 1.24–3.53) in the last six months.
Conclusion
The data suggest that the pharmacy users were at a less "advanced" stage of their injection career and had lower HIV prevalence than SEP users. This suggests that pharmacies could be utilized as a site for providing additional HIV prevention messages, services for IDUs and in linking IDUs with existing harm reduction services.
doi:10.1186/1477-7517-6-3
PMCID: PMC2653475  PMID: 19232088
9.  Expanded syringe exchange programs and reduced HIV infection among new injection drug users in Tallinn, Estonia 
BMC Public Health  2011;11:517.
Background
Estonia has experienced an HIV epidemic among intravenous drug users (IDUs) with the highest per capita HIV prevalence in Eastern Europe. We assessed the effects of expanded syringe exchange programs (SEP) in the capital city, Tallinn, which has an estimated 10,000 IDUs.
Methods
SEP implementation was monitored with data from the Estonian National Institute for Health Development. Respondent driven sampling (RDS) interview surveys with HIV testing were conducted in Tallinn in 2005, 2007 and 2009 (involving 350, 350 and 327 IDUs respectively). HIV incidence among new injectors (those injecting for < = 3 years) was estimated by assuming (1) new injectors were HIV seronegative when they began injecting, and (2) HIV infection occurred at the midpoint between first injection and time of interview.
Results
SEP increased from 230,000 syringes exchanged in 2005 to 440,000 in 2007 and 770,000 in 2009. In all three surveys, IDUs were predominantly male (80%), ethnic Russians (>80%), and young adults (mean ages 24 to 27 years). The proportion of new injectors decreased significantly over the years (from 21% in 2005 to 12% in 2009, p = 0.005). HIV prevalence among all respondents stabilized at slightly over 50% (54% in 2005, 55% in 2007, 51% in 2009), and decreased among new injectors (34% in 2005, 16% in 2009, p = 0.046). Estimated HIV incidence among new injectors decreased significantly from 18/100 person-years in 2005 and 21/100 person-years in 2007 to 9/100 person-years in 2009 (p = 0.026).
Conclusions
In Estonia, a transitional country, a decrease in the HIV prevalence among new injectors and in the numbers of people initiating injection drug use coincided with implementation of large-scale SEPs. Further reductions in HIV transmission among IDUs are still required. Provision of 70 or more syringes per IDU per year may be needed before significant reductions in HIV incidence occur.
doi:10.1186/1471-2458-11-517
PMCID: PMC3146432  PMID: 21718469
10.  High-prevalence and high-estimated incidence of HIV infection among new injecting drug users in Estonia: need for large scale prevention programs 
Objective
To examine HIV risk behavior and HIV infection among new injectors in Tallinn, Estonia.
Design and methods
Data from two cross-sectional surveys of injecting drug users (IDUs) recruited from a syringe exchange program (N = 162, Study 1) or using respondent driven sampling (N = 350, Study 2). Behavioral surveys were administered; serum samples were collected for HIV testing. Subjects were categorized into new injectors (injecting ≤ 3 years) and long-term injectors (injecting > 3 years).
Results
Twenty-eight of 161 (17%, Study 1) and 73/350 (21%, Study 2) of the study subjects were new injectors. HIV infection was substantial among the newer injectors: HIV prevalence was 50% (Study 1) and 34% (Study 2), and estimated HIV incidence 31/100 PY and 21/100 PY, respectively. In Study 2, new injectors were more likely to be female and ethnic Estonian and less likely to be injecting daily compared with long-term injectors. No significant difference was found among two groups on sharing injecting equipment or reported number of sexual partners.
Conclusions
A continuing HIV epidemic among new injectors is of critical public health concern. Interventions to prevent initiation into injecting drug use and scaling up HIV prevention programs for IDUs in Estonia are of utmost importance.
doi:10.1093/pubmed/fdn014
PMCID: PMC2925676  PMID: 18308743
Estonia; HIV; IDU; injection drug use; new injecting drug users
11.  High prevalence of blood-borne virus infections and high-risk behaviour among injecting drug users in Tallinn, Estonia 
Summary
The HIV epidemic in Estonia is rapidly expanding, and injection drug users (IDUs) are the major risk group contributing to the expansion. A convenience sample of 159 IDUs visiting syringe-exchange programmes (SEPs) was selected to quantify the association of HIV-risk behaviours and blood-borne infections. A high prevalence of HIV, hepatitis B core antibody (HBVcore), hepatitis B surface antigen (HbsAg) and hepatitis C virus antibodies (56, 85.1, 21.3, and 96.2%, respectively) was associated with high-risk injections, unsafe sexual behaviour and alcohol abuse. These findings emphasize the importance of evidence-based secondary prevention among the HIV-infected, especially given the uncertain sustainability of antiretroviral and substance abuse treatments.
doi:10.1258/095646207779949907
PMCID: PMC2925660  PMID: 17326862
injection drug use; HIV; HBV; HCV; high-risk behaviour; Estonia
12.  Estonia at the Threshold of the Fourth Decade of the AIDS Era in Europe 
Abstract
This article describes the trends of HIV/AIDS and related conditions in Estonia during the past decade (2000–2009), with special focus on the potential for epidemic transition. Key transmission determinants and major risk groups are examined and problems and barriers to fighting HIV/AIDS with possible applications in prevention and control are described. Estonian routine data sources and published literature were reviewed, supplemented with information from personal communication with physicians and public health specialists. For comparative European data, international HIV/AIDS and drug addiction surveillance documents, administrative data, and published literature were reviewed. In Eastern Europe (including Estonia) the predominant HIV transmission mode is injection drug use (IDU), closely followed by heterosexual transmission, an increasing risk factor for new cases. Although the contribution of cases acquired by sexual contact with high-risk partners such as IDUs is not known, characteristics of the sexual networks of IDUs may be important in determining the evolution of the HIV/AIDS epidemics in the region. In Estonia, despite major gaps in available data, the HIV/AIDS epidemic is still presumably confined to IDUs (and probably, to their sexual partners). In Eastern Europe, young women in IDU–non-IDU partnerships engaging in unprotected sex potentially serve as a bridge to the general population, yet knowledge of and research into the population characteristics and potential magnitude of bridging are limited. In Estonia, as in other Eastern European countries, HIV prevention and harm reduction initiatives should be tailored not only to the predominantly male HIV-positive IDU population, but also to their noninfected non-IDU female sexual partners.
doi:10.1089/aid.2010.0223
PMCID: PMC3180763  PMID: 21142588
13.  Estimating Incidence from Prevalence in Generalised HIV Epidemics: Methods and Validation 
PLoS Medicine  2008;5(4):e80.
Background
HIV surveillance of generalised epidemics in Africa primarily relies on prevalence at antenatal clinics, but estimates of incidence in the general population would be more useful. Repeated cross-sectional measures of HIV prevalence are now becoming available for general populations in many countries, and we aim to develop and validate methods that use these data to estimate HIV incidence.
Methods and Findings
Two methods were developed that decompose observed changes in prevalence between two serosurveys into the contributions of new infections and mortality. Method 1 uses cohort mortality rates, and method 2 uses information on survival after infection. The performance of these two methods was assessed using simulated data from a mathematical model and actual data from three community-based cohort studies in Africa. Comparison with simulated data indicated that these methods can accurately estimates incidence rates and changes in incidence in a variety of epidemic conditions. Method 1 is simple to implement but relies on locally appropriate mortality data, whilst method 2 can make use of the same survival distribution in a wide range of scenarios. The estimates from both methods are within the 95% confidence intervals of almost all actual measurements of HIV incidence in adults and young people, and the patterns of incidence over age are correctly captured.
Conclusions
It is possible to estimate incidence from cross-sectional prevalence data with sufficient accuracy to monitor the HIV epidemic. Although these methods will theoretically work in any context, we have able to test them only in southern and eastern Africa, where HIV epidemics are mature and generalised. The choice of method will depend on the local availability of HIV mortality data.
Timothy Hallett and colleagues develop and test two user-friendly methods to estimate HIV incidence based on changes in cross-sectional prevalence, using either mortality rates or survival after infection.
Editors' Summary
Background.
More than 25 million people have died from AIDS and about 33 million people are currently infected with human immunodeficiency virus (HIV, the virus that causes AIDS). Faced with this threat to human health, governments and international agencies are working together to halt the AIDS epidemic. An important part of this effort is HIV surveillance. The spread of HIV needs to be monitored to assess the impact of interventions (for example, the provision of antiretroviral drugs) and to plan for current and future health care needs. HIV surveillance in countries where the epidemic has spread beyond specific groups into the whole population (a generalized epidemic) has mainly relied on determining the prevalence of HIV infection (the fraction of the population that is infected) among women attending antenatal clinics. Recently, however, household health surveys (for example, the Demographic and Health Surveys) have begun to use blood testing for antibodies to the AIDS virus (serological testing) to provide more accurate estimates of HIV prevalence in the general adult population.
Why Was This Study Done?
Although prevalence estimates provide useful information about the HIV epidemic, another important indicator is incidence—the number of new infections occurring during a specific time period. Incidence measurements provide more information about temporal changes in the epidemic and transmission patterns and allow public-health experts to make better predictions of future health care needs. But, whereas prevalence can be measured with anonymized serological surveys, individuals would have to be identified and followed up in repeat serological surveys to provide a direct measurement of incidence. This is expensive and hard to achieve in many settings. In this study, therefore, the researchers develop and validate two mathematical methods to estimate HIV incidence in generalized HIV epidemics from prevalence data.
What Did the Researchers Do and Find?
Changes in the fraction of the population living with HIV (prevalence) can occur not only because of changes in the rate of new infections (incidence), but also because mortality rates are much higher for infected individuals than others. The researchers' methods disentangle the contributions to HIV prevalence (as measured in serological surveys) made by new infections from those due to deaths from AIDS and other causes. Their first method incorporates information on death rates collected in cohort studies of HIV infection (cohort studies investigate outcomes in groups of people); their second method uses information on survival after HIV infection, also collected in long-running cohort studies. The accuracy of both methods was assessed using computer-simulated data and actual data on HIV prevalence and incidence collected in three community-based cohort studies in Zimbabwe and Uganda (countries with generalized but declining HIV epidemics) and Tanzania (a country with a generalized, stable epidemic). Both methods provided accurate estimates of HIV incidence from the simulated data. Using the data collected in Africa, the mean difference between actual measurements of incidence and the estimate provided by method 1 was 19%; for method 2 it was 14%. In addition, the measured and estimated incidences were in good agreement for all age groups.
What Do These Findings Mean?
These findings suggest HIV incidence rates can be estimated from repeat surveys of prevalence with sufficient accuracy to monitor the HIV epidemic. The accuracy of the estimates across all age groups is particularly important because knowledge of the age-related risk pattern provides the information on transmission patterns that is needed to design effective intervention programs. Because these methods were tested using data only from southern and eastern Africa where the HIV epidemic is mature and generalized, they may not work as well in regions where the epidemic is restricted to subsets of the population. Other factors that might affect their accuracy include the amount of international migration and the uptake of antiretroviral therapies. Nevertheless, with the increased availability of serial measurements of serological prevalence, these new methods for estimating HIV incidence from HIV prevalence could prove extremely useful for monitoring the progress of national HIV epidemics and for guiding HIV control programs. The authors include spreadsheets that can be used to calculate incidence by either method from consecutive survey data.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050080.
The US National Institute of Allergy and Infectious Diseases provides information on HIV infection and AIDS
The US Centers for Disease Control and Prevention provides information on global HIV/AIDS topics (in English and Spanish)
The HIV InSite provides comprehensive and up-to-date information on all aspects of HIV/AIDS from the University of California San Francisco, including country reports on the AIDS epidemic in 195 countries, including Uganda, Zimbabwe, and Tanzania
Avert, an international AIDS charity, provides information on all aspects of HIV/AIDS, including fact sheets on understanding HIV and AIDS statistics, and on HIV and AIDS in Africa
The Demographic and Health Surveys program collects, analyzes, and disseminates information on health and population trends in countries around the world
doi:10.1371/journal.pmed.0050080
PMCID: PMC2288620  PMID: 18590346
14.  The Cost and Impact of Scaling Up Pre-exposure Prophylaxis for HIV Prevention: A Systematic Review of Cost-Effectiveness Modelling Studies 
PLoS Medicine  2013;10(3):e1001401.
Gabriela Gomez and colleagues systematically review cost-effectiveness modeling studies of pre-exposure prophylaxis (PrEP) for preventing HIV transmission and identify the main considerations to address when considering the introduction of PrEP to HIV prevention programs.
Background
Cost-effectiveness studies inform resource allocation, strategy, and policy development. However, due to their complexity, dependence on assumptions made, and inherent uncertainty, synthesising, and generalising the results can be difficult. We assess cost-effectiveness models evaluating expected health gains and costs of HIV pre-exposure prophylaxis (PrEP) interventions.
Methods and Findings
We conducted a systematic review comparing epidemiological and economic assumptions of cost-effectiveness studies using various modelling approaches. The following databases were searched (until January 2013): PubMed/Medline, ISI Web of Knowledge, Centre for Reviews and Dissemination databases, EconLIT, and region-specific databases. We included modelling studies reporting both cost and expected impact of a PrEP roll-out. We explored five issues: prioritisation strategies, adherence, behaviour change, toxicity, and resistance. Of 961 studies retrieved, 13 were included. Studies modelled populations (heterosexual couples, men who have sex with men, people who inject drugs) in generalised and concentrated epidemics from Southern Africa (including South Africa), Ukraine, USA, and Peru. PrEP was found to have the potential to be a cost-effective addition to HIV prevention programmes in specific settings. The extent of the impact of PrEP depended upon assumptions made concerning cost, epidemic context, programme coverage, prioritisation strategies, and individual-level adherence. Delivery of PrEP to key populations at highest risk of HIV exposure appears the most cost-effective strategy. Limitations of this review include the partial geographical coverage, our inability to perform a meta-analysis, and the paucity of information available exploring trade-offs between early treatment and PrEP.
Conclusions
Our review identifies the main considerations to address in assessing cost-effectiveness analyses of a PrEP intervention—cost, epidemic context, individual adherence level, PrEP programme coverage, and prioritisation strategy. Cost-effectiveness studies indicating where resources can be applied for greatest impact are essential to guide resource allocation decisions; however, the results of such analyses must be considered within the context of the underlying assumptions made.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year approximately 2.5 million people are infected with HIV, the virus that causes AIDS. Behavioral strategies like condom use and reduction of sexual partners have been the hallmarks of HIV prevention efforts. However, biological prevention measures have also recently been shown to be effective. These include male circumcision, treatment as prevention (treating HIV-infected people with antiretroviral drugs to reduce transmission), and pre-exposure prophylaxis (PrEP), where people not infected with HIV take antiretroviral drugs to reduce the probability of transmission. Strategies such as PrEP may be viable prevention measure for couples in long-term relationships where one partner is HIV-positive and the other is HIV-negative (HIV serodiscordant couples) or groups at higher risk of HIV infection, such as men who have sex with men, and injection drug users.
Why Was This Study Done?
The findings from recent clinical trials that demonstrate PrEP can reduce HIV transmission have led to important policy discussions and in the US, Southern Africa, and the UK new clinical guidelines have been developed on the use of PrEP for the prevention of HIV infection. For those countries that are considering whether to introduce PrEP into HIV prevention programs, national policy and decision makers need to determine potential costs and health outcomes. Cost-effectiveness models—mathematical models that simulate cost and health effects of different interventions—can help inform such decisions. However, the cost-effectiveness estimates that could provide guidance for PrEP programs are dependent on, and limited by, the assumptions included in the models, which can make their findings difficult to generalize. A systematic comparison of published cost-effectiveness models of HIV PrEP interventions would be useful for policy makers who are considering introducing PrEP intervention programs.
What Did the Researchers Do and Find?
The researchers performed a systematic review to identify published cost-effectiveness models that evaluated the health gains and costs of HIV PrEP interventions. Systematic reviews attempt to identify, appraise, and synthesize all the empirical evidence that meets pre-specified eligibility criteria to answer a given research question by using explicit methods aimed at minimizing bias. By searching databases the authors identified 13 published studies that evaluated the impact of PrEP in different populations (heterosexual couples, men who have sex with men, and injection drug users) in different geographic settings, which included Southern Africa, Ukraine, US, and Peru.
The authors identified seven studies that assessed the introduction of PrEP into generalized HIV epidemics in Southern Africa. These studies suggest that PrEP may be a cost effective intervention to prevent heterosexual transmission. However, the authors note that funding PrEP while other cost-effective HIV prevention methods are underfunded in this setting may have high opportunity costs. The authors identified five studies where PrEP was introduced for concentrated epidemics among men who have sex with men (four studies in the US and one in Peru). These studies suggest that PrEP may have a substantial impact on the HIV epidemic but may not be affordable at current drug prices. The authors also identified a single study that modeled the introduction of PrEP for people who inject drugs in the Ukraine, which found PrEP not to be cost effective.
In all settings the price of antiretroviral drugs was found to be a limiting factor in terms of affordability of PrEP programs. Behavioral changes and adherence to PrEP were estimated to have potentially significant impacts on program effectiveness but the emergence of drug resistance or PrEP-related toxicity did not significantly affect cost-effectiveness estimates. Several PrEP prioritization strategies were explored in included studies and delivering PrEP to populations at highest risk of HIV exposure was shown to improve cost-effectiveness estimates. However, the extra costs of identifying and engaging with high-risk populations were not taken into consideration. The authors note that the geographic coverage of identified studies was limited and that the findings are very dependent on the setting which limits generalizability.
What Do these Findings Mean?
These findings suggest that PrEP could be a cost-effective tool to reduce new HIV infections in some settings. However, the cost-effectiveness of PrEP is dependent upon cost, the epidemic context, program coverage and prioritization strategies, participants' adherence to the drug regimen, and PrEP efficacy estimates. These findings will aid decision makers quantify and compare the reductions in HIV incidence that could be achieved by implementing a PrEP program.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001401.
The US National Institute of Allergy and Infectious Diseases has information on HIV/AIDS
aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and has a section on PrEP
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including HIV prevention
AVAC Global Advocacy for HIV Prevention provides information on HIV prevention, including PrEP
The US Centers for Disease Control and Prevention also has information on PrEP
The World Health Organization has a page on its WHO-CHOICE criteria for cost-effectiveness
doi:10.1371/journal.pmed.1001401
PMCID: PMC3595225  PMID: 23554579
15.  Factors influencing quality of life of people living with HIV in Estonia: a cross-sectional survey 
Background
Identification of factors that determine quality of life is important in order to better tailor health and social care services, and thereby improve the functioning and well being of people living with HIV. The estimated number of people living with HIV in eastern Europe and central Asia is 1.6 million. Little is known about the quality of life of people living with HIV in this region. The main purpose of the present study was to identify the factors influencing quality of life in a sample of HIV-infected persons in Estonia.
Methods
A convenient sample of 451 patients attending three infectious diseases clinics for routine HIV clinical care visits was recruited for a cross-sectional survey. The World Health Organization's Quality of Life HIV instrument was used to measure quality of life of the participants and medical data was abstracted from clinical records.
Results
Good overall quality of life was reported by 42.6% (95% CI: 38.0–47.2%) of the study participants (53% men, 60% self-identify as injecting drug users, 82% <30 years of age, 30% with CD4+ T cell count <300 cells/mm3, and 22% on antiretroviral treatment). We identified the following variables as independent predictors of good overall quality of life: being currently employed or studying (AOR: 2.27, 95% CI: 1.18–4.38); and the absence of HIV-related symptoms (AOR: 2.31, 95% CI: 1.24–4.29).
Conclusion
A comprehensive and competent care system, including health care providers and social workers, is required for an effective response. In addition, social interventions should seek to enhance the economic and employment opportunities for people living with HIV in the region.
doi:10.1186/1758-2652-12-13
PMCID: PMC2717916  PMID: 19607721
16.  Should Pharmacists have a Role in Harm Reduction Services for IDUs? A Qualitative Study in Tallinn, Estonia 
Despite the high number of injecting drug users (IDUs) in Estonia, little is known about involving pharmacies into human immunodeficiency virus (HIV) prevention activities and potential barriers. Similarly, in other Eastern European countries, there is a need for additional sources for clean syringes besides syringe exchange programmes (SEPs), but data on current practices relating to pharmacists’ role in harm reduction strategies is scant. Involving pharmacies is especially important for several reasons: they have extended hours of operation and convenient locations compared to SEPs, may provide access for IDUs who have avoided SEPs, and are a trusted health resource in the community. We conducted a series of focus groups with pharmacists and IDUs in Tallinn, Estonia, to explore their attitudes toward the role of pharmacists in HIV prevention activities for IDUs. Many, but not all, pharmacists reported a readiness to sell syringes to IDUs to help prevent HIV transmission. However, negative attitudes toward IDUs in general and syringe sales to them specifically were identified as important factors restricting such sales. The idea of free distribution of clean syringes or other injecting equipment and disposal of used syringes in pharmacies elicited strong resistance. IDUs stated that pharmacies were convenient for acquiring syringes due to their extended opening hours and local distribution. IDUs were positive toward pharmacies, although they were aware of stigma from pharmacists and other customers. They also emphasized the need for distilled water and other injection paraphernalia. In conclusion, there are no formal or legislative obstacles for providing HIV prevention services for IDUs at pharmacies. Addressing negative attitudes through educational courses and involving pharmacists willing to be public health educators in high drug use areas would improve access for HIV prevention services for IDUs.
doi:10.1007/s11524-009-9400-5
PMCID: PMC2791822  PMID: 19921542
Injecting drug users; Pharmacists; Harm reduction services
17.  Public-Health and Individual Approaches to Antiretroviral Therapy: Township South Africa and Switzerland Compared 
PLoS Medicine  2008;5(7):e148.
Background
The provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland.
Methods and Findings
We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/μl in South Africa and 204 cells/μl in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%–97%) in South Africa and 96% (94%–97%) in Switzerland, and 26% (22%–29%) and 27% (24%–31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81–19.2) during months 1–3 and 1.77 (0.90–3.50) during months 4–24.
Conclusions
Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease.
Comparing HIV treatment in Switzerland, where drug selection is individualized, and South Africa, where a programmatic approach is used, Matthias Egger and colleagues find similar virologic outcomes over two years.
Editors' Summary
Background.
Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since the first reported case in 1981, and more than 30 million people are now infected with the human immunodeficiency virus (HIV), which causes AIDS. HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected people died within 10 years of becoming infected. Then, in 1996, highly active antiretroviral therapy (HAART)—a combination of several antiretroviral drugs—was developed. Now, in resource-rich countries, clinicians provide individually tailored care for HIV-infected people by prescribing combinations of antiretroviral drugs chosen from more than 20 approved medicines. The approach to treatment of HIV in developed countries typically also includes frequent monitoring of the amount of virus in patients' blood (viral load), viral resistance testing (to see whether any viruses are resistant to specific antiretroviral drugs), and regular CD4 cell counts (an indication of immune-system health). Since the implementation of these interventions, the health and life expectancy of people with HIV has improved dramatically in these countries.
Why Was This Study Done?
The history of HIV care in resource-poor countries has been very different. Initially, these countries could not afford to provide HAART for their populations. In 2003, however, governments, international agencies, and funding bodies began to implement plans to increase HAART coverage in developing countries. By December 2006, more than a quarter of the HIV-infected people in low- and middle-income countries who urgently needed treatment were receiving HAART. However, instead of individualized treatment, HAART programs in developing countries follow a public-health approach developed by the World Health Organization. That is, drug regimens, clinical decision-making, and clinical and laboratory monitoring are all standardized. This public-health approach takes into account the realities of under-resourced health systems, but is it as effective as the individualized approach? The researchers addressed this question by comparing virologic responses (the effect of treatment on the viral load), changes to first-line (initial) therapy, and deaths in patients receiving HAART in South Africa (public-health approach) and in Switzerland (individualized approach).
What Did the Researchers Do and Find?
The researchers analyzed data collected since 2001 from more than 2,000 patients enrolled in HAART programs in two townships (Gugulethu and Khayelitsha) in Cape Town, South Africa, and from more than 1,000 patients enrolled in the Swiss HIV Cohort Study, a nationwide study of HIV-infected people. The patients in South Africa, who had a lower starting CD4 cell count and were more likely to have advanced AIDS than the patients in Switzerland, started their treatment for HIV infection with one of four first-line therapies, and about a quarter changed to a second-line therapy during the study. By contrast, 36 first-line regimens were used in Switzerland and half the patients changed to a different regimen. Despite these differences, the viral load was greatly reduced within a year in virtually all the patients and viral rebound (an increased viral load after a low measurement) developed within 2 years in a quarter of the patients in both countries. However, more patients died in South Africa than in Switzerland, particularly during the first 3 months of therapy.
What Do These Findings Mean?
These findings suggest that the public-health approach to HAART practiced in South Africa is as effective in terms of virologic outcomes as the individualized approach practiced in Switzerland. This is reassuring because it suggests that “antiretroviral anarchy” (the unregulated use of antiretroviral drugs, interruptions in drug supplies, and the lack of treatment monitoring), which is likely to lead to the emergence of viral resistance, is not happening in South Africa as some experts feared it might. Thus, these findings support the continued rollout of the public-health approach to HAART in resource-poor countries. Conversely, they also suggest that a more standardized approach to HAART could be taken in Switzerland (and in other industrialized countries) without compromising its effectiveness. Finally, the higher mortality in South Africa than in Switzerland, which partly reflects the many patients in South Africa in desperate need of HAART and their more advanced disease at the start of therapy, suggests that HIV-infected patients in South Africa and in other resource-limited countries would benefit from earlier initiation of therapy.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050148.
The World Health Organization provides information about universal access to HIV treatment (in several languages) and on its recommendations for a public-health approach to antiretroviral therapy for HIV infection
More details on the Swiss HIV Cohort Study and on the studies in Gugulethu and Khayelitsha are available
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS, including detailed information about antiretroviral therapy and links to treatment guidelines for various countries
Information is available from Avert, an international AIDS charity, on HIV and AIDS around the world and on providing AIDS drug treatment for millions
doi:10.1371/journal.pmed.0050148
PMCID: PMC2443185  PMID: 18613745
18.  The Impact of Monitoring HIV Patients Prior to Treatment in Resource-Poor Settings: Insights from Mathematical Modelling 
PLoS Medicine  2008;5(3):e53.
Background
The roll-out of antiretroviral treatment (ART) in developing countries concentrates on finding patients currently in need, but over time many HIV-infected individuals will be identified who will require treatment in the future. We investigated the potential influence of alternative patient management and ART initiation strategies on the impact of ART programmes in sub-Saharan Africa.
Methods and Findings
We developed a stochastic mathematical model representing disease progression, diagnosis, clinical monitoring, and survival in a cohort of 1,000 hypothetical HIV-infected individuals in Africa. If individuals primarily enter ART programmes when symptomatic, the model predicts that only 25% will start treatment and, on average, 6 life-years will be saved per person treated. If individuals are recruited to programmes while still healthy and are frequently monitored, and CD4+ cell counts are used to help decide when to initiate ART, three times as many are expected to be treated, and average life-years saved among those treated increases to 15. The impact of programmes can be improved further by performing a second CD4+ cell count when the initial value is close to the threshold for starting treatment, maintaining high patient follow-up rates, and prioritising monitoring the oldest (≥ 35 y) and most immune-suppressed patients (CD4+ cell count ≤ 350). Initiating ART at higher CD4+ cell counts than WHO recommends leads to more life-years saved, but disproportionately more years spent on ART.
Conclusions
The overall impact of ART programmes will be limited if rates of diagnosis are low and individuals enter care too late. Frequently monitoring individuals at all stages of HIV infection and using CD4 cell count information to determine when to start treatment can maximise the impact of ART.
Using a stochastic model based on data from Africa, Timothy Hallett and colleagues find that starting HIV treatment based on regular CD4 monitoring, rather than on symptoms, would substantially increase survival.
Editors' Summary
Background.
Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since the first case in 1981, and about 33 million people are currently infected with the human immunodeficiency virus (HIV), which causes AIDS. HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-positive individuals died within 10 years but in 1996, combination antiretroviral therapy (ART)—a mixture of powerful but expensive antiretroviral drugs—was developed. For HIV-positive people living in affluent, developed countries who could afford ART, AIDS then became a chronic disease, but for those living in low- and middle-income countries it remained a death sentence—ART was too expensive. In 2003, this lack of access to ART was declared a global health emergency and governments, international organizations, and funding bodies began to implement plans to increase ART coverage in developing countries.
Why Was This Study Done?
The roll-out of ART in developing countries has concentrated so far on finding HIV-positive people who currently need treatment. In developing countries, these are often individuals who have AIDS-related symptoms such as recurrent severe bacterial infections. But healthy people are also being diagnosed as HIV positive during voluntary testing and at antenatal clinics. How should these HIV-positive but symptom-free individuals be managed? Should regular health-monitoring appointments be scheduled for them and when should ART be initiated? Management decisions like these will determine how well patients do when they eventually start ART, as well as the demand for ART and other health-care services. The full range of alternative patient management strategies cannot be tested in clinical trials—it would be unethical—but public-health officials need an idea of their relative effectiveness in order to use limited resources wisely. In this study, therefore, the researchers use mathematical modeling to investigate the impact of alternative patient management and ART initiation strategies on the impact of ART programs in resource-poor settings.
What Did the Researchers Do and Find?
The researchers' mathematical model, which includes data on disease progression collected in Africa, simulates disease progression in a group (cohort) of 1,000 HIV-infected adults. It tracks these individuals from infection, through diagnosis and clinical monitoring, and into treatment and predicts how many will receive ART and their length of survival under different management scenarios and ART initiation rules. The model predicts that if HIV-positive individuals receive ART only when they have AIDS-related symptoms, only a quarter of them will ever start ART and the average life-years saved per person treated will be 6 years (that is, they will live 6 years longer than they would have done without treatment). If individuals are recruited to ART programs when they are healthy and are frequently monitored using CD4 cell counts to decide when to start ART, three-quarters of the cohort will be treated and 15 life-years will be saved per person treated. The impact of ART programs will be increased further, the model predicts, by preferentially monitoring people who are more than 35 years old and the most immunosuppressed individuals. Finally, strategies that measure CD4 cells frequently will save more life-years because ART is more likely to be started before the immune system is irreversibly damaged. Importantly for resource-poor settings, these strategies also save more life-years per year on ART.
What Do These Findings Mean?
As with all mathematical models, the accuracy of these predictions depends on the assumptions built into the model and the reliability of the data fed into it. Also, this model does not estimate the costs of the various management options, something that will need to be done to ensure effective allocation of limited resources. Nevertheless, these findings provide several general clues about how ART programs should be implemented in poor countries to maximize their effects. Early diagnosis of infections, regular monitoring of patients, and using CD4 cell counts to decide when to initiate ART should all help to improve the number of life-years saved by ART. In other words, the researchers conclude, effectively managing individuals at all stages of HIV infection is essential to maximize the impact of ART.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/doi:10.1371/journal.pmed.0050053.
Information from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS.
Information from the US Centers for Disease Control and Prevention on global HIV/AIDS topics (in English and Spanish)
HIV InSite, comprehensive and up-to-date information on all aspects of HIV/AIDS from the University of California, San Francisco
Information from Avert, an international AIDS charity, on HIV and AIDS in Africa and on HIV/AIDS treatment and care, including universal access to ART
Progress toward universal access to HIV/AIDS treatment, the latest report from the World Health Organization (available in several languages)
Guidelines for antiretroviral therapy in adults and adolescents are provided by the World Health Organization and by the US Department of Health and Human Services
doi:10.1371/journal.pmed.0050053
PMCID: PMC2265759  PMID: 18336064
19.  Integration and co-location of HIV/AIDS, tuberculosis and drug treatment services 
Injection drug use (IDU) plays a critical role in the HIV epidemic in several countries throughout the world. In these countries, injection drug users are at significant risk for both HIV and tuberculosis, and active IDU negatively impacts treatment access, adherence and retention. Comprehensive strategies are therefore needed to effectively deliver preventive, diagnostic and curative services to these complex patient populations. We propose that developing co-located integrated care delivery systems should become the focus of national programmes as they continue to scale-up access to antiretroviral medications for drug users. Existing data suggest that such a programme will expand services for each of these diseases; increase detection of tuberculosis (TB) and HIV; improve medication adherence; increase entry into substance use treatment; decrease the likelihood of adverse drug events; and improve the effectiveness of prevention interventions. Key aspects of integration programmes include: co-location of services convenient to the patient; provision of effective substance use treatment, including pharmacotherapies; cross-training of generalist and specialist care providers; and provision of enhanced monitoring of drug-drug interactions and adverse side effects. Central to implementing this agenda will be fostering the political will to fund infrastructure and service delivery, expanding street-level outreach to IDUs, and training community health workers capable of cost effectively delivering these services.
doi:10.1016/j.drugpo.2007.03.001
PMCID: PMC2696234  PMID: 17689379
HIV; AIDS; Injection drug use; Substance use; Tuberculosis; Health care integration; Health services; Prevention
20.  Impact of Antiretroviral Therapy on Incidence of Pregnancy among HIV-Infected Women in Sub-Saharan Africa: A Cohort Study 
PLoS Medicine  2010;7(2):e1000229.
A multicountry cohort study in sub-Saharan Africa by Landon Myer and colleagues reveals higher pregnancy rates in HIV-infected women on antiretroviral therapy (ART).
Background
With the rapid expansion of antiretroviral therapy (ART) services in sub-Saharan Africa there is growing recognition of the importance of fertility and childbearing among HIV-infected women. However there are few data on whether ART initiation influences pregnancy rates.
Methods and Findings
We analyzed data from the Mother-to-Child Transmission-Plus (MTCT-Plus) Initiative, a multicountry HIV care and treatment program for women, children, and families. From 11 programs in seven African countries, women were enrolled into care regardless of HIV disease stage and followed at regular intervals; ART was initiated according to national guidelines on the basis of immunological and/or clinical criteria. Standardized forms were used to collect sociodemographic and clinical data, including incident pregnancies. Overall 589 incident pregnancies were observed among the 4,531 women included in this analysis (pregnancy incidence, 7.8/100 person-years [PY]). The rate of new pregnancies was significantly higher among women receiving ART (9.0/100 PY) compared to women not on ART (6.5/100 PY) (adjusted hazard ratio, 1.74; 95% confidence interval, 1.19–2.54). Other factors independently associated with increased risk of incident pregnancy included younger age, lower educational attainment, being married or cohabiting, having a male partner enrolled into the program, failure to use nonbarrier contraception, and higher CD4 cell counts.
Conclusions
ART use is associated with significantly higher pregnancy rates among HIV-infected women in sub-Saharan Africa. While the possible behavioral or biomedical mechanisms that may underlie this association require further investigation, these data highlight the importance of pregnancy planning and management as a critical but neglected component of HIV care and treatment services.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Human immunodeficiency virus (HIV) causes Acquired Immunodeficiency Syndrome (AIDS), which is a major global cause of disease and death. More than 33 million people around the world are infected with HIV, with nearly 5,500 dying daily from HIV and AIDS-related complications. HIV/AIDS is especially problematic in sub-Saharan Africa, where it is the leading cause of death. There is no cure for HIV/AIDS, but medicines known as “antiretroviral therapy” (ART) can prolong life and reduce complications in patients infected with HIV. 97% of patients with HIV/AIDS live in low- and middle-income countries. According to the World Health Organization, nearly 10 million of these patients need ART. As patients' access to treatment is often hindered by the high cost and low availability of ART, global health efforts have focused on promoting ART use in resource-limited nations. Such efforts also increase awareness of how HIV is spread (contact with blood or semen, in sexual intercourse, sharing needles, or from mother to child during childbirth). ART reduces, but does not remove, the chance of a mother's passing HIV to her child during birth.
Why Was This Study Done?
By the end of 2007, 3 million HIV-infected patients in poor countries were receiving ART. Many of those treated with ART are young women of child-bearing age. Childbirth is an important means of spreading HIV in sub-Saharan Africa, where 60% of all HIV patients are women. This study questions whether the improved health and life expectancy that results from treatment with ART affects pregnancy rates of HIV-infected patients. The study explores this question in seven African countries, by examining the rates of pregnancy in HIV-infected women before and after they started ART.
What Did the Researchers Do and Find?
The authors looked at the records of 4,531 HIV-infected women enrolled in the Mother-to-Child-Transmission-Plus (MTCT-Plus) Initiative in seven African countries. MTCT -Plus, begun in 2002, is a family-centered treatment program that offers regular checkups, blood tests, counseling, and ART treatment (if appropriate) to women and their families. At each checkup, women's CD4+ cell counts and World Health Organization guidelines were used to determine their eligibility for starting ART. Over a 4-year period, nearly a third of the women starting ART experienced a pregnancy: 244 pregnancies occurred in the “pre-ART” group (women not receiving ART) compared to 345 pregnancies in the “on-ART” group (women receiving ART). The chance of pregnancy increased over time in the on-ART group to almost 80% greater than the pre-ART group, while remaining relatively low and constant in the pre-ART group. The authors noted that, as expected, other factors also increased the chances of pregnancy, including younger age, lower educational status, and use of nonbarrier contraception such as injectable hormones.
What Do These Findings Mean?
This study suggests that starting ART is associated with higher pregnancy rates in sub-Saharan Africa, nearly doubling the chances of a woman becoming pregnant. The reasons for this link are unclear. One possible explanation is behavioral: women receiving ART may feel more motivated to have children as their health and quality of life improve. However, the study did not examine how pregnancy desires and sexual activity of women changed while on ART, and cannot discern why ART is linked to increased pregnancy. By using pregnancy data gathered from patient questionnaires rather than laboratory tests, the study is limited by the possibility of inaccurate patient reporting. Understanding how pregnancy rates vary in HIV-infected women receiving ART helps support the formation of responsive, effective HIV programs. Female HIV patients of child-bearing age, who form the majority of patients receiving ART in sub-Saharan Africa, would benefit from programs that combine starting HIV treatment with ART with education and contraception counseling and pregnancy-related care.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000229.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS, including a list of articles and other sources of information about the primary care of adolescents with HIV
A UNAIDS 2008 report is available on the global AIDS epidemic
The International Planned Parenthood Foundation provides information on sexual and reproductive health and HIV
The International Center for AIDS Care and Treatment Programs at the Columbia University Mailman School of Public health provides information to assist HIV care and treatment programs in resource-limited settings
doi:10.1371/journal.pmed.1000229
PMCID: PMC2817715  PMID: 20161723
21.  Commentary on Vorobjov et al., "Comparison of injection drug users who obtain syringes from pharmacies and syringe exchange programs in Tallinn, Estonia" 
Recent data suggest that globally, between 5% and 10% of all new HIV cases are the result of unsafe injecting practices, and experts agree that reducing these practices is key to tackling the spread of HIV. And yet, despite the overwhelming evidence that providing sterile syringes to injection drug users (IDU) through syringe exchange programs (SEPs) or other means is an effective way of reducing HIV transmission among high-risk subpopulations, IDU in most settings still do not have access to sterile injecting equipment or if they do, access remains too restricted to effectively reduce the risk of HIV transmission. Vorobjov and colleagues have presented in this journal an interesting and timely study from Estonia comparing individuals who obtain syringes from SEPs and those who obtain syringes from pharmacies. As the authors point out, Estonia faces an unacceptably high HIV incidence rate of 50 new HIV cases per 100,000, this rate driven primarily by injection drug use. As such, the authors argue that Estonia's SEP network does not have the capacity to serve a growing IDU population at risk of transmitting HIV and pharmacy dispensation of clean syringes may be one potential approach to decreasing syringe sharing among high-risk injectors. It may be overly optimistic to consider the impact of higher threshold interventions such as pharmacy-based SEPs, given that IDU populations that engage in HIV risk behaviours such as syringe sharing are often hidden or hard to reach. Despite the need for a cautious approach, however, the findings presented by Vorobjov et al. may chart one potential course towards a more comprehensive societal response to reducing the health harms associated with injection drug use.
doi:10.1186/1477-7517-6-33
PMCID: PMC2789049  PMID: 19943944
22.  Optimizing Care for HIV-Infected People Who Use Drugs: Evidence-Based Approaches to Overcoming Healthcare Disparities 
People who use drugs experience delayed HIV diagnosis, reduced entry into and retention in care, delayed initiation of antiretroviral therapy, and inferior HIV outcomes. Overcoming healthcare disparities requires evidence-based, comprehensive packages of clinical/social services, including treatment for substance use disorders.
Substance use disorders (SUDs) and human immunodeficiency virus (HIV) are pervasive epidemics that synergize, resulting in negative outcomes for HIV-infected people who use drugs (PWUDs). The expanding epidemiology of substance use demands a parallel evolution of the HIV specialist—beyond HIV to diagnosis and management of comorbid SUDs. The purpose of this paper is to describe healthcare disparities for HIV-infected PWUDs along each point of a continuum of care, and to suggest evidence-based strategies for overcoming these healthcare disparities. Despite extensive dedicated resources and availability of antiretroviral therapy (ART) in the United States, PWUDs continue to experience delayed HIV diagnosis, reduced entry into and retention in HIV care, delayed initiation of ART, and inferior HIV treatment outcomes. Overcoming these healthcare disparities requires integrated packages of clinical, pharmacological, behavioral, and social services, delivered in ways that are cost-effective and convenient and include, at a minimum, screening for and treatment of underlying SUDs.
doi:10.1093/cid/cit427
PMCID: PMC3792721  PMID: 23797288
HIV; substance use disorders; healthcare disparities; treatment; engagement in care
23.  Adherence to HAART: A Systematic Review of Developed and Developing Nation Patient-Reported Barriers and Facilitators 
PLoS Medicine  2006;3(11):e438.
Background
Adherence to highly active antiretroviral therapy (HAART) medication is the greatest patient-enabled predictor of treatment success and mortality for those who have access to drugs. We systematically reviewed the literature to determine patient-reported barriers and facilitators to adhering to antiretroviral therapy.
Methods and Findings
We examined both developed and developing nations. We searched the following databases: AMED (inception to June 2005), Campbell Collaboration (inception to June 2005), CinAhl (inception to June 2005), Cochrane Library (inception to June 2005), Embase (inception to June 2005), ERIC (inception to June 2005), MedLine (inception to June 2005), and NHS EED (inception to June 2005). We retrieved studies conducted in both developed and developing nation settings that examined barriers and facilitators addressing adherence. Both qualitative and quantitative studies were included. We independently, in duplicate, extracted data reported in qualitative studies addressing adherence. We then examined all quantitative studies addressing barriers and facilitators noted from the qualitative studies. In order to place the findings of the qualitative studies in a generalizable context, we meta-analyzed the surveys to determine a best estimate of the overall prevalence of issues. We included 37 qualitative studies and 47 studies using a quantitative methodology (surveys). Seventy-two studies (35 qualitative) were conducted in developed nations, while the remaining 12 (two qualitative) were conducted in developing nations. Important barriers reported in both economic settings included fear of disclosure, concomitant substance abuse, forgetfulness, suspicions of treatment, regimens that are too complicated, number of pills required, decreased quality of life, work and family responsibilities, falling asleep, and access to medication. Important facilitators reported by patients in developed nation settings included having a sense of self-worth, seeing positive effects of antiretrovirals, accepting their seropositivity, understanding the need for strict adherence, making use of reminder tools, and having a simple regimen. Among 37 separate meta-analyses examining the generalizability of these findings, we found large heterogeneity.
Conclusions
We found that important barriers to adherence are consistent across multiple settings and countries. Research is urgently needed to determine patient-important factors for adherence in developing world settings. Clinicians should use this information to engage in open discussion with patients to promote adherence and identify barriers and facilitators within their own populations.
An analysis of qualitative and quantitative studies found consistent barriers to adherence to HIV therapy across multiple settings and countries, ranging from access to medication to problems with complicated regimens.
Editors' Summary
Background.
The World Health Organization has estimated that in 2005, about 38 million people worldwide were living with HIV/AIDS; the mortality caused by HIV/AIDS is very high. Antiretroviral drugs are effective at controlling the disease and extending life span. However, it is important for people to stick to the drug regimens exactly in order to keep levels of HIV low, prevent it from becoming resistant to drugs, and stop the illness from progressing. However, many people find it very difficult to take antiretroviral drugs precisely as they should. There is already some evidence from research studies on the reasons why this is the case. There are two different research approaches taken by these studies: “qualitative” methods, which try to find out about attitudes and behaviors using focus groups, interviews, or other techniques; and “quantitative” methods, which try to find out about peoples' opinions and experience using surveys with set questions for the participants to answer, and then count the different responses.
Why Was This Study Done?
The investigators wanted to put together all of the available evidence from published research studies (called doing a “systematic review”) on which factors affected people's adherence to antiretroviral drugs. They wanted to do a systematic review because it is thought to be a very rigorous way of appraising all the available evidence (although there is considerable debate about the value of using such a method to analyze the results of qualitative research).
What Did the Researchers Do and Find?
The study team searched biomedical literature databases as well as conference abstracts and research registries using a defined set of search queries. They screened all the scientific papers they found; those reporting results of original research into factors affecting antiretroviral adherence were then analyzed in more detail. 84 relevant studies were identified, of which 37 used “qualitative” methods (focus groups, interviews, open-ended questioning) and 47 used “quantitative” methods (surveys). Most of these studies had been carried out in the developed world. Then, the researchers extracted the factors affecting adherence from the original studies, which could be either “positive” factors (helping adherence) or “negative” ones (making adherence more difficult). They classified the factors into four key themes: “patient related” (e.g., seeing positive results, fear of disclosure, being depressed); “beliefs about medication” (e.g., faith in how well the drugs worked, side effects); “daily schedules” (e.g., using reminder tools, disruptions to routine); and “interpersonal relationships” (e.g., trusting relations with health-care provider; social isolation).
  Many barriers to adherence were common to both developed and developing settings. Some factors were unique to the studies conducted in the developing world, such as financial constraints and problems with traveling to get access to treatment. Fear of disclosure was an important barrier identified in many of the studies.
What Do These Findings Mean?
The researchers combined the results of many different studies and identified factors that help or obstruct adherence to antiretroviral treatment. By identifying influences common to the different settings, greater weight can be placed on the factors that were identified. Only 12 of the studies included in this research were from the developing world, where the majority of HIV/AIDS patients live; hence more work is needed to examine and address the factors influencing antiretroviral adherence in these parts of the world. This study provides researchers and health policy makers with a starting point for changes that might help to ensure greater adherence to antiretroviral treatment.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030438.
Medline Plus information on AIDS medicines (Medline Plus is a service of the US National Library of Medicine and the National Institutes of Health)
Joint United Nations Programme on HIV/AIDS has information about the state of the HIV/AIDS epidemic worldwide
The World Health Organization has an HIV/AIDS program site providing comprehensive information on the HIV/AIDS epidemic worldwide
The World Health Organization pages on antiretroviral therapy
doi:10.1371/journal.pmed.0030438
PMCID: PMC1637123  PMID: 17121449
24.  Early and Late Direct Costs in a Southern African Antiretroviral Treatment Programme: A Retrospective Cohort Analysis 
PLoS Medicine  2009;6(12):e1000189.
Gary Maartens and colleagues describe the direct heath care costs and identify the drivers of cost over time in an HIV managed care program in Southern Africa.
Background
There is a paucity of data on the health care costs of antiretroviral therapy (ART) programmes in Africa. Our objectives were to describe the direct heath care costs and establish the cost drivers over time in an HIV managed care programme in Southern Africa.
Methods/Findings
We analysed the direct costs of treating HIV-infected adults enrolled in the managed care programme from 3 years before starting non-nucleoside reverse transcriptase inhibitor-based ART up to 5 years afterwards. The CD4 cell count criterion for starting ART was <350 cells/µl. We explored associations between variables and mean total costs over time using a generalised linear model with a log-link function and a gamma distribution. Our cohort consisted of 10,735 patients (59.4% women) with 594,497 mo of follow up data (50.9% of months on ART). Median baseline CD4+ cell count and viral load were 125 cells/µl and 5.16 log10 copies/ml respectively. There was a peak in costs in the period around ART initiation (from 4 mo before until 4 mo after starting ART) driven largely by hospitalisation, following which costs plateaued for 5 years. The variables associated with changes in mean total costs varied with time. Key early associations with higher costs were low baseline CD4+ cell count, high baseline HIV viral load, and shorter duration in HIV care prior to starting ART; whilst later associations with higher costs were lower ART adherence, switching to protease inhibitor-based ART, and starting ART at an older age.
Conclusions
Drivers of mean total costs changed considerably over time. Starting ART at higher CD4 counts or longer pre-ART care should reduce early costs. Monitoring ART adherence and interventions to improve it should reduce later costs. Cost models of ART should take into account these time-dependent cost drivers, and include costs before starting ART.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 30 million people (22 million people in sub-Saharan Africa alone) are infected with the human immunodeficiency virus (HIV), the cause of acquired immunodeficiency syndrome (AIDS). HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, on average HIV-positive people died within 10 years of infection. Then, in 1996, highly active antiretroviral therapy (ART; combinations of powerful antiretroviral drugs) was developed. For people living in affluent, developed countries HIV/AIDS became a chronic, treatable condition, but for the millions of HIV-infected people living in low- and middle-income countries, effective treatment was unavailable and HIV/AIDS remained a fatal illness. In 2003, this situation was declared a global health emergency and governments, international agencies, and funding bodies began to implement plans to increase ART coverage in developing countries. By the end of 2008, of the 9.5 million people in need of ART in low- and middle-income countries, more than 4 million people were receiving treatment.
Why Was This Study Done?
Good progress is being made towards achieving universal access to ART, partly because the cost of antiretroviral drugs has plummeted in developing countries. But the provision of antiretroviral drugs is not the only direct cost associated with ART. General practitioner, specialist, and maternity-related care for patients receiving ART, hospital accommodation when necessary, and the investigations that are needed to monitor the progress of HIV infection such as CD4 cell counts and viral load measurements all incur considerable costs. To use their limited resources effectively, public-health officials in developing countries need to know as much as possible about the direct costs of HIV health care but few studies have investigated these costs, particularly those incurred before an individual starts taking ART. In this study, the researchers explore health care costs in a South African private-sector HIV/AIDS program and examine the variables that drive the costs of HIV health care around the time of ART initiation and during later phases of ART.
What Did the Researchers Do and Find?
The researchers analyzed the direct costs of treating more than 100,000 HIV-infected adults enrolled in a private HIV care program in South Africa from 3 years before they started ART until up to 5 years after ART initiation; within this program, individuals began to receive ART when their CD4 cell count fell below 350 cells/µl of blood. The researchers found a peak in direct health costs from 4 months before to 4 months after starting ART (the “peri-ART” period), which was driven mainly by hospital costs. After the peri-ART period, costs dropped (although not to the levels seen before this period) and stabilized at an intermediate level for the next 5 years. Detailed statistical analyses suggest that the key variables associated with higher costs in the peri-ART period were a low baseline CD4 cell count, a high baseline HIV viral load, and a shorter time in HIV care before ART initiation. The key variable associated with higher costs later in ART was lower adherence to the drug therapy. That is, costs were higher among patients who did not take their antiretroviral drugs regularly.
What Do These Findings Mean?
This study involved patients enrolled in a private health care program in which the criteria for initiating ART differed somewhat from those recommended by the World Health Organization for ART initiation in resource-limited settings. Thus, the absolute mean total costs calculated by the researchers are unlikely to be generalizable to public HIV care systems in South Africa and in other resource-poor settings. However, the finding that the drivers of mean total costs change considerably over time may be generalizable and provides some useful information for public-health planners that can now be tested in other, more resource-limited patient populations. In particular, the findings of this study suggest that the high early costs of ART programs could be reduced by starting ART at higher CD4 cell counts or by providing longer pre-ART care. In addition, the findings suggest that monitoring ART adherence and introducing interventions to improve ART adherence could reduce the later direct costs of ART programs.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000189.
Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on the HIV and AIDS in Africa, and on universal access to AIDS treatment (in English and Spanish)
The World Health Organization provides information about universal access to AIDS treatment, including the September 2009 progress report (in English and French)
The US Centers for Disease Control and Prevention also provides information on global efforts to deal with the HIV/AIDS epidemic
doi:10.1371/journal.pmed.1000189
PMCID: PMC2777319  PMID: 19956658
25.  Alcohol use and incarceration adversely affect HIV-1 RNA suppression among injection drug users starting antiretroviral therapy 
We conducted this study among HIV-infected injection drug users to determine the effect of self-reported alcohol use and prior incarceration at the time of initiating antiretroviral therapy on subsequent HIV-1 RNA suppression. We examined the demographics, recent incarceration history, and drug and alcohol use history from the Vancouver Injection Drug User Study (VIDUS) questionnaire closest to the date of initiating antiretroviral therapy. We linked these data to the HIV/AIDS Drug Treatment Program. There were 234 VIDUS participants who accessed antiretroviral therapy through the Drug Treatment Program from August 1, 1996, to July 31, 2001. In terms of illicit drug use, 196 (84%) reported injecting heroin and cocaine at the time of initiating antiretroviral therapy. Multiple logistic regression revealed that in the 6 months prior to initiating antiretroviral therapy, alcohol use (adjusted odds ratio [AOR] 0.32; 95% CI 0.13–0.81) and incarceration (AOR 0.22; 95% CI 0.09–0.58) were independently associated with lower odds of HIV-1 RNA suppression. Factors positively associated with HIV-1 RNA suppression included: adherence (AOR 1.27; 95% CI 1.06–1.51); lower baseline HIV-1 RNA (AOR 1.30: 95% CI 1.01–1.66); highly active antiretroviral therapy (AOR 4.10; 95% CI 1.56–10.6); months on therapy (AOR 1.1; 95% CI 1.06–1.14). Among HIV-infected injection drug users who were on antiretroviral therapy, any alcohol use and incarceration in the 6 months prior to initiating antiretroviral therapy were negatively associated with achieving HIV-1 RNA suppression. In addition to addition treatment for active heroin and cocaine use, the identification and treatment of alcohol problems should be supported in this setting. As well, increased outreach to HIV-infected drug users recently released from prison to ensure continuity of care needs to be further developed.
doi:10.1093/jurban/jtg073
PMCID: PMC3456224  PMID: 14709714
Anti-HIV agents; HIV infections; Human; Logistic regression models; Substance abuse; Intravenous; Alcohol; Prison

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