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1.  Immune Reconstitution Inflammatory Syndrome following Antiretroviral Therapy Initiation in Tuberculosis Patients: Findings from the SAPiT Trial 
Annals of internal medicine  2012;157(5):313-324.
Concerns about immune reconstitution inflammatory syndrome (IRIS) remain a barrier to antiretroviral therapy (ART) initiation during anti-tuberculosis treatment in co-infected patients.
We assessed IRIS incidence, severity, and outcomes relative to timing of ART initiation in patients with HIV-related tuberculosis (HIV-TB).
An outpatient clinic in Durban, South Africa
642 HIV-TB co-infected patients
In a secondary analysis of the SAPiT trial, IRIS was assessed in patients randomized to initiate ART either within four weeks of tuberculosis treatment initiation (early integrated-treatment arm), within four weeks of completion of the intensive phase of tuberculosis treatment (late integrated-treatment arm) or within four weeks after tuberculosis therapy completion (sequential-treatment arm). IRIS was defined as new onset or worsening symptoms, signs or radiographic manifestations temporally related to treatment initiation accompanied by a treatment response. IRIS severity, hospitalization and time to resolution were monitored.
IRIS incidence was 19.5 (n=43), 7.5 (n=18) and 8.1 (n=19) per 100 person-years in the early integrated-, late integrated-, and sequential-treatment arms, respectively; P < 0.001, and 45.5, 9.7 and 19.7 per 100 person-years in patients with baseline CD4+ counts <50 cells/mm3, P = 0.004. IRIS incidence was higher in the early integrated- compared to the late integrated- (incidence rate ratio (IRR) = 2.6, 95%confidence interval (CI): 1.5 to 4.8; P < 0.001) or sequential-treatment arm (IRR=2.4, 95%CI: 1.4 to 4.4; P < 0.001). IRIS cases in the early integrated-treatment arm were more severe (34.9% vs. 18.9%, P = 0.18); had significantly higher hospitalization rates (18/43 vs. 5/37; P = 0.01), and longer time to resolution (70.5 vs. 29.0 days; P = 0.001) compared to IRIS cases in the other two arms.
IRIS could not be assessed, due to LTFU, withdrawal or death within 6 months of scheduled ART initiation, in more patients from the sequential treatment arm (n=74) than in the late integrated treatment arm (n=50) and in the early integrated treatment arm (n=32). This study did not assess IRIS risk in non-ambulant patients and in patients with extra-pulmonary and smear negative pulmonary tuberculosis.
Initiation of ART early during tuberculosis treatment resulted in significantly higher IRIS rates, with longer time to resolution, and more severe cases of IRIS requiring hospitalization. These findings, particularly relevant to patients initiating ART with CD4+ counts < 50 cells/mm3, need to be considered together with the increased survival benefit of early ART initiation in this group. NCT00398996
PMCID: PMC3534856  PMID: 22944873
3.  Scale-up of HIV Treatment Through PEPFAR: A Historic Public Health Achievement 
Since its inception in 2003, the US President’s Emergency Plan for AIDS Relief (PEPFAR) has been an important driving force behind the global scale-up of HIV care and treatment services, particularly in expansion of access to antiretroviral therapy. Despite initial concerns about cost and feasibility, PEPFAR overcame challenges by leveraging and coordinating with other funders, by working in partnership with the most affected countries, by supporting local ownership, by using a public health approach, by supporting task-shifting strategies, and by paying attention to health systems strengthening. As of September 2011, PEPFAR directly supported initiation of antiretroviral therapy for 3.9 million people and provided care and support for nearly 13 million people. Benefits in terms of prevention of morbidity and mortality have been reaped by those receiving the services, with evidence of societal benefits beyond the anticipated clinical benefits. However, much remains to be accomplished to achieve universal access, to enhance the quality of programs, to ensure retention of patients in care, and to continue to strengthen health systems.
PMCID: PMC3445041  PMID: 22797746
4.  Relationship of Postprandial Nonesterified Fatty Acids, Adipokines, and Insulin Across Gender in Human Immunodeficiency Virus–Positive Patients Undergoing Highly Active Antiretroviral Therapy 
Metabolic derangements are common in human immunodeficiency virus (HIV)-positive subjects undergoing antiretroviral therapy, but little is known about postprandial conditions.
We investigated the relationship between leptin, adiponectin, nonesterified fatty acids (NEFA), and insulin in response to a day-long meal pattern and evaluated gender differences in HIV-positive men (n = 12) and women (n = 13) undergoing highly active antiretroviral therapy (HAART).
For both men and women, a significant decrease in postprandial NEFA levels was observed following breakfast (0.53 vs. 0.22 mmol/L, P < 0.001, baseline and at 3 hours, respectively), whereas day-long postprandial leptin and adiponectin levels showed small nonsignificant oscillations. In contrast to NEFA and adiponectin, postprandial leptin levels were significantly higher among women compared to men (P < 0.05). Postprandial NEFA levels correlated positively with fasting insulin levels (r2 = 0.25, P = 0.016), and the postbreakfast decrease in NEFA levels correlated significantly with the postbreakfast increase in insulin levels (r2 = 0.17, P = 0.038). No significant association between postprandial adipokines and insulin was observed.
In HAART-treated, HIV-infected men and women, levels of NEFA, but not adipokines, showed significant postprandial variation. Furthermore, food intake resulted in significant NEFA suppression in proportion to the food-stimulated insulin increase.
PMCID: PMC3135887  PMID: 19320559
5.  The Link4Health study to evaluate the effectiveness of a combination intervention strategy for linkage to and retention in HIV care in Swaziland: protocol for a cluster randomized trial 
Gaps in the HIV care continuum contribute to suboptimal individual health outcomes and increased risk of HIV transmission at the population level. Implementation science studies are needed to evaluate clinic-based interventions aimed at improving retention of patients across the continuum.
Link4Health uses an unblended cluster site-randomized design to evaluate the effectiveness of a combination intervention strategy (CIS) as compared to standard of care on linkage to and retention in care among HIV-diagnosed adults in Swaziland. The CIS intervention targets a multiplicity of structural, behavioral, and biomedical barriers through five interventions: (1) point-of-care CD4 testing at time of HIV testing, (2) accelerated antiretroviral therapy (ART) initiation for eligible patients, (3) mobile phone appointment reminders, (4) care and prevention packages, and (5) non-cash financial incentives for linkage and retention. The unit of randomization is a network of HIV clinics inclusive of a secondary facility coupled with an affiliated primary facility. Ten study units were randomized based on implementing partner, geographic location, and historic volume of HIV patients. Target enrollment was 2200 individuals, each to be followed for 12 months. Eligibility criteria includes HIV-positive test, age >18 years, willing to receive HIV care at a clinic in the study unit and consent to study procedures. Exclusion criteria included previous HIV care in the past 6 months, planning to leave the community, and current pregnancy.
The primary study outcome is linkage within 1 month and retention at 12 months after testing HIV positive. Secondary outcomes include viral load suppression at 12 months, time to ART eligibility and initiation, participant acceptability, and cost-effectiveness. The trial status is that study enrollment is complete and follow-up procedures are ongoing.
Link4Health evaluates a novel and pragmatic combination intervention strategy to improve linkage to and retention in care among adults with HIV in Swaziland. If the strategy is found to be effective, this study has the potential to inform HIV service delivery in resource-limited settings.
Trial registration NCT01904994
PMCID: PMC4506770  PMID: 26189154
HIV; Linkage; Retention
6.  A Paradigm Shift: Focus on the HIV Prevention Continuum 
The human immunodeficiency virus (HIV) prevention continuum is a framework that illustrates the interconnectedness of each step in the spectrum of prevention services, while emphasizing that all steps are needed to decrease HIV acquisition and transmission. This continuum, similar to the HIV care continuum, begins with HIV testing followed by linkage of HIV-uninfected persons to prevention services, retention in such services, and adherence to prevention interventions with repeated HIV testing to monitor for HIV acquisition. To advance the global goal of zero new HIV infections, individuals must receive the entire continuum of prevention services, and no partial credit can be given to achievement of one step in isolation of all steps in the continuum.
PMCID: PMC4141493  PMID: 24926026
HIV; prevention; continuum of care
7.  Antiretroviral Therapy for the Prevention of HIV Transmission: What Will It Take? 
The promise of antiretroviral therapy (ART) for prevention requires attention to every step of the human immunodeficiency virus (HIV) care continuum, from expanding HIV testing to linkage to and retention in care, to prompt initiation of ART for eligible persons, to virologic suppression.
The evidence in support of use of antiretroviral therapy (ART) for prevention of human immunodeficiency virus (HIV) transmission is encouraging and has stimulated optimism for achieving a dramatic change in the trajectory of the HIV epidemic. Yet, there are substantial challenges that, if not addressed, could be the Achilles’ heel for this concept. These challenges require strengthening every step of the HIV care continuum, including expansion of HIV testing to reach all those with HIV infection, effective linkage to and retention in care, timely initiation of ART, and high levels of treatment adherence with viral load suppression. Also important is the identification of individuals with acute HIV infection whose contribution to HIV transmission may be substantial. Implementation research is needed to identify strategies that address these challenges and to determine the efficacy of ART for prevention in key populations as well as to evaluate the effectiveness of combination strategies for HIV prevention at the population level.
PMCID: PMC3952607  PMID: 24429438
HIV; prevention; antiretroviral therapy
8.  HIV Prevention: Great Achievements, More Challenges Ahead 
PMCID: PMC3717370  PMID: 23764621
HIV Prevention; Research Agenda
9.  HIV Acquisition Among Women From Selected Areas of the United States 
Annals of internal medicine  2013;158(1):10-18.
Women account for 23% of newly diagnosed HIV infections in the United States, but there are few recent, well-characterized cohorts of U.S. women in whom behavior characteristics and HIV acquisition have been well-described.
To evaluate HIV incidence and describe behaviors among U.S. women residing in areas of high HIV prevalence.
Multisite, longitudinal cohort of women who had HIV rapid testing and audio computer-assisted self-interviews at baseline and every 6 months for up to 12 months. ( NCT00995176)
10 urban and periurban communities with high HIV prevalence and poverty rates, located in the northeastern and southeastern United States.
Venue-based sampling was used to recruit women aged 18 to 44 years who recently had unprotected sex and had 1 or more additional personal or partner risk factors and no self-reported previous HIV diagnosis.
HIV prevalence and incidence, frequency of HIV risk behaviors, and health status perceptions.
Among 2099 high-risk women (85.9% black and 11.7% of Hispanic ethnicity), 32 (1.5%) were diagnosed with HIV infection at enrollment. Annual HIV incidence was 0.32% (95% CI, 0.14% to 0.74%). Older age, substance use, and knowing a partner had HIV were associated with HIV prevalence. Ten women died during the study (0.61% per year).
Longitudinal assessment of risk behaviors was limited to a maximum of 12 months. There were few incident HIV infections, precluding identification of characteristics predictive of HIV acquisition.
This study enrolled a cohort of women with HIV incidence substantially higher than the Centers for Disease Control and Prevention national estimate in the general population of U.S. black women. Concerted efforts to improve preventive health care strategies for HIV and overall health status are needed for similar populations.
PMCID: PMC4033695  PMID: 23277896
10.  HIV and people who use drugs in central Asia: Confronting the perfect storm 
Drug and alcohol dependence  2013;132(0 1):S2-S6.
PMCID: PMC4006578  PMID: 23953656
11.  Lessons Learned from Africa 
Delayed access to HIV care and treatment in sub-Saharan Africa meant that the early years of HIV scale-up were characterized by a largely North-to-South transfer of knowledge and resources. Clinicians from wealthy countries were amongst the first to gain experience with antiretroviral treatment and care of people living with HIV, and shared key lessons with their colleagues in sub-Saharan Africa when widespread access to HIV services became available. Ten years later, South-to-North lessons learned from the remarkable achievements of HIV programs in Africa now have the potential to inform the response to the US domestic epidemic.
PMCID: PMC3561635  PMID: 21406985
HIV scale-up; program implementation; lessons; Africa
12.  Challenges of a Hidden Epidemic: HIV Prevention among Women in the United States 
HIV/AIDS trends in the United States depict a concentrated epidemic with hot spots that vary by location, poverty, race/ethnicity, and transmission mode. HIV/AIDS is a leading cause of death among US women of color; two thirds of new infections among women occur in black women, despite the fact that black women account for just 14% of the US female population. The gravity of the HIV epidemic among US women is often not appreciated by those at risk as well as by the broader scientific community. We summarize the current epidemiology of HIV/AIDS among US women and discuss clinical, research, and public health intervention components that must be brought together in a cohesive plan to reduce new HIV infections in US women. Only by accelerating research and programmatic efforts will the hidden epidemic of HIV among US women emerge into the light and come under control.
PMCID: PMC3551266  PMID: 21406990
HIV in women; HIV prevention science; racial disparity
13.  Integration of Antiretroviral Therapy with Tuberculosis Treatment 
The New England journal of medicine  2011;365(16):1492-1501.
We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, optimal time to initiate ART during tuberculosis treatment remains contentious.
To address this, we conducted a 3-arm, open-label randomized controlled trial in South Africa in acid-fast bacilli smear positive patients (n=642) with HIV and CD4+ counts <500 cells/mm3. Findings on the early therapy group (ART initiated within 4 weeks of tuberculosis treatment initiation, n=214) and late therapy group (ART initiated within the first 4 weeks of the continuation phase of tuberculosis treatment, n=215) are presented here.
Median CD4+ count and viral load at baseline was 150 cells/mm3 and 161000 copies/ml, being similar in both groups. Incidence rate of AIDS or death was 6.9 (18/259.4) and 7.8 (19/244.2) per 100 person-years in the early and late therapy groups respectively (Incidence Rate Ratio (IRR)=0.89; 95%Confidence Interval (95%CI): 0.44,1.79; P=0.73). However, in patients with CD4+ counts <50 cells/mm3, the incidence rates of AIDS or death were 8.5 (early) and 26.3 (late) per 100 person-years (IRR=0.32; 95%CI: 0.07,1.13; P=0.06). Immune reconstitution inflammatory syndrome (IRIS) incidence rates were 20.2 (early) and 7.7 (late) per 100 person-years (IRR=2.62; 95%CI: 1.48,4.82; P<0.001). Adverse events requiring antiretroviral drug switches occurred in 10 (early) and 1 (late) patients (P=0.006).
The benefits of AIDS-free survival balanced against the risks of IRIS and ART-related adverse events, support early ART initiation in patients with CD4+ counts <50 cells/mm3 and deferred ART initiation to the continuation phase of tuberculosis treatment when CD4+ counts are higher.
PMCID: PMC3233684  PMID: 22010915
14.  Patients Enrolled in HIV Care in Mozambique: Baseline Characteristics and Follow-Up Outcomes 
To utilize routinely collected service delivery data from HIV care and treatment clinics in Mozambique to describe the patient population and programmatic outcomes from 2003 to 2009.
Data from patient charts were entered into an electronic database at 28 clinics in 5 Mozambican provinces. Patients’ characteristics at enrollment in HIV care and at antiretroviral therapy (ART) initiation were examined. We calculated a corrected 12-month mortality estimate using a recently developed nomogram for sub-Saharan African ART patients.
A total of 154,188 HIV-infected individuals (10,164 children <15 years old) were enrolled in HIV care services between 2003 and 2009. Of the 51,269 (36%) adults who started ART, 35% initiated ART with CD4 count <100 cells per microliter and 14.4% with World Health Organization stage IV. Just more than 10% (10.5%) of women were documented to be pregnant at enrollment. One-third of the 3,745 (37%) children who initiated ART were <2 years old, and 53%of those <5 years initiated ART severely immunosuppressed (CD4% <15%). Thirty-five percent of all children and 30% of those initiating ART met the definition of severe malnourishment (weight-for-age Z score <−3). Among those who initiated ART, the median estimated 12-month mortality rate across sites was 13.1% (interquartile range: 11.5%–16.0%) and 13.5% (interquartile range: 11.4%–17.4%) for adults and children, respectively.
A substantial number of HIV-infected patients have been enrolled in HIV care and initiated on ART, with many patients having advanced HIV disease. With the release of new guidelines for ART use for adults, pregnant women, and children, extensive efforts are needed to ensure more timely initiation of ART.
PMCID: PMC3422887  PMID: 21725246
antiretroviral treatment; HIV/AIDS; HIV care; implementation science; Mozambique; operations research; PEPFAR; scale-up
15.  Association of Adherence Support and Outreach Services with Total Attrition, Loss to Follow-Up, and Death among ART Patients in Sub-Saharan Africa 
PLoS ONE  2012;7(6):e38443.
Loss to follow-up (LTF) after antiretroviral therapy (ART) initiation is common in HIV clinics. We examined the effect of availability of adherence support and active patient outreach services on patient attrition following ART initiation.
Methods and Findings
This ecologic study examined clinic attrition rates (total attrition, LTF, and death) among 232,389 patients initiating ART at 349 clinics during 2004–2008 in 10 sub-Saharan African countries, and cohort attrition (proportion retained at 6 and 12 months after ART initiation) among a subset of patients with follow-up information (n = 83,389). Log-linear regression compared mean rates of attrition, LTF, and death between clinics with and without adherence support and outreach services. Cumulative attrition, LTF, and death rates were 14.2, 9.2, and 4.9 per 100 person-years on ART, respectively. In multivariate analyses, clinic availability of >2 adherence support services was marginally associated with lower attrition rates (RRadj = 0.59, 95%CI: 0.35–1.0). Clinics with availability of counseling services (RRadj = 0.62, 95%CI: 0.42–0.92), educational materials (RRadj = 0.73, 95%CI: 0.63–0.85), reminder tools (RRadj = 0.79, 95%CI: 0.64–0.97), and food rations (RRadj = 0.72, 95%CI: 0.58–0.90) had significantly lower attrition, with similar results observed for LTF. Outreach services were not significantly associated with attrition. In cohort analyses, attrition was significantly lower at clinics offering >2 adherence support services (RRadj,6m = 0.84, 95%CI: 0.73–0.96), dedicated pharmacy services (RRadj,6m = 0.78, 95%CI: 0.69–0.90), and active patient outreach (RRadj,6m = 0.85, 95%CI: 0.73–0.99). Availability of food rations was marginally associated with increased retention at 6 (RRadj,6m  = 0.82, 95%CI: 0.64–1.05) but not 12 months (RRadj,12m  = 0.98, 95%CI: 0.78–1.21).
Availability of adherence support services, active patient outreach and food rations at HIV care clinics may improve retention following ART initiation.
PMCID: PMC3369888  PMID: 22685569
16.  Factors Associated with Late Antiretroviral Therapy Initiation among Adults in Mozambique 
PLoS ONE  2012;7(5):e37125.
Despite recent changes to expand the ART eligibility criteria in sub-Saharan Africa, many patients still initiate ART in the advanced stages of HIV infection, which contributes to increased early mortality rates, poor patient outcomes, and onward transmission.
To evaluate individual and clinic-level factors associated with late ART initiation in Mozambique, we conducted a retrospective sex-specific analysis of data from 36,411 adult patients who started ART between January 2005 and June 2009 at 25 HIV clinics in Mozambique. Late ART initiation was defined as CD4 count<100 cells/µL or WHO stage IV. Mixed effects models were used to identify patient- and clinic-level factors associated with late ART initiation.
The proportion of patients initiating ART late decreased from 46% to 37% during 2005–2007, but remained constant (between 37–33%) from 2007–2009. Of those who initiated ART late (median CD4 = 57 cells/µL), 5% were known to have died and 54% were lost to clinic within 6 months of ART initiation (compared with 2% and 47% among other patients starting ART [median CD4 = 192 cells/µL]). In multivariate analysis, female sex and pregnancy at ART initiation (AORfemale_not_pregnant_vs._male = 0.66, 95%CI [0.62–0.69]; AORpregnant_vs._non_pregnant = 0.60, 95%CI [0.49–0.73]), younger and older age (AOR15–25_vs.26–30 = 0.86, 95%CI [0.79–0.94], AOR>45_vs.26–30 = 0.72, 95%CI [0.67–0.77]), entry into care via PMTCT (AORentry_through_PMTCT_vs.VCT = 0.42, 95%CI [0.35–0.50]), marital status (AORmarried/in union_vs.single = 0.87, 95%CI [0.83–0.92]), education (AORsecondary_or_higher_vs.primary = 0.87, 95%CI [0.83–0.93]) and year of ART initiation were associated with a lower likelihood of late ART initiation. Clinic-level factors independently associated with a lower likelihood of late ART initiation included CD4 machine on-site (AORCD4_machine_onsite_vs.offsite = 0.83, 95%CI [0.74–0.94]) and presence of PMTCT services onsite (AOR = 0.85, 95%CI [0.77–0.93]).
The risk of starting ART late remained persistently high. Efforts are needed to ensure identification and enrollment of patients at earlier stages of HIV disease. Individual and clinic level factors identified may provide clues for upstream structural interventions.
PMCID: PMC3352894  PMID: 22615917
17.  Use of HIV Case Surveillance System to Design and Evaluate Site-Randomized Interventions in an HIV Prevention Study: HPTN 065 
The Open AIDS Journal  2012;6:122-130.
Modeling studies suggest intensified HIV testing, linkage-to-care and antiretroviral treatment to achieve viral suppression may reduce HIV transmission and lead to control of the epidemic. To study implementation of strategy, population-level data are needed to monitor outcomes of these interventions. US HIV surveillance systems are a potential source of these data.
HPTN065 (TLC-Plus) Study is evaluating the feasibility of a test, linkage-to-care, and treat strategy for HIV prevention in two intervention communities - the Bronx, NY, and Washington, DC. Routinely collected laboratory data on diagnosed HIV cases in the national HIV surveillance system were used to select and randomize sites, and will be used to assess trial outcomes.
To inform study randomization, baseline data on site-aggregated study outcomes was provided from HIV surveillance data by New York City and Washington D.C. Departments of Health. The median site rate of linkage-to-care for newly diagnosed cases was 69% (IQR 50%-86%) in the Bronx and 54% (IQR 33%-71%) in Washington, D.C. In participating HIV care sites, the median site percent of patients with viral suppression (<400 copies/mL) was 57% (IQR 53%-61%) in the Bronx and 64% (IQR 55%-72%) in Washington, D.C.
In a novel use of site-aggregated surveillance data, baseline data was used to design and evaluate site randomized studies for both HIV test and HIV care sites. Surveillance data have the potential to inform and monitor sitelevel health outcomes in HIV-infected patients.
PMCID: PMC3462339  PMID: 23049660
HIV; linkage-to-care; site randomized; surveillance; test and treat; viral load suppression.
18.  Antiretroviral Therapy: A Promising HIV Prevention Strategy? 
The use of antiretroviral therapy (ART) has been associated with significant improvement in morbidity and survival of persons living with HIV. In addition, recently, there has also been intense interest in the potential impact of ART on HIV transmission and consequently on the trajectory of the HIV epidemic globally. Evidence from mathematical modeling analyses as well as observational, and ecological studies supports the potential for ART as prevention. However, definitive data from clinical trials are awaited.
In the United States, the feasibility and potential of using ART as a prevention strategy presents particular challenges: the large number of individuals with undiagnosed HIV; the predominance of disenfranchised individuals affected by the epidemic; evidence of delay in engagement in HIV care after diagnosis with attendant late initiation of ART; and difficulties with consistent, long-term adherence to ART as well as concerns regarding long-term risk-behavior change. Thus, for this novel effort to succeed, a multidimensional approach is necessary that must include policy changes, social mobilization, and improved access to clinical and supportive services for persons living with HIV, with a particular focus on the unique needs of at-risk populations, combined with engagement of all cadres of health care providers and community constituencies.
PMCID: PMC3074403  PMID: 21406980
HIV treatment; antiretroviral therapy; transmission; prevention
19.  Addressing HIV prevention research priorities in the United States 
More than half a million Americans became newly infected with HIV in the first decade of the new millennium. The domestic epidemic has had the heaviest impact on men who have sex with men (MSM) and people from racial and ethnic minority populations, particularly African-Americans. For example, Black MSM represent <1% of the U.S. population but 25% of the new HIV cases, as per CDC estimates published in 2008. While Black and Hispanic women constitute 24% of all U.S. women, they accounted for 82% of HIV cases in women in 2005, based on data from 33 states with confidential name-based reporting. There is a nearly 23-fold higher rate of AIDS diagnoses for Black women (45.5/100,000 women) and nearly 6-fold higher rate for Hispanic women (11.2/100,000) compared to the rate for white women (2.0/100,000). Investigators from the HIV Prevention Trials Network (HPTN), an NIH-sponsored collaborative clinical trials group, have crafted a domestic research agenda with community input. Two new domestic studies are in progress (2009) and a community-based clinical trial feasibility effort is in development (2010 start date). These studies focus on outreach, testing, and treatment of infected persons as a backbone for HIV prevention. Reaching persons not receiving health message and service with novel approaches to both prevention and care/treatment is an essential priority for HIV control in the U.S.; our research is designed to guide the best approaches and assess the impact of bridging treatment and prevention.
PMCID: PMC2862583  PMID: 20397942
HIV; prevention; United States; homosexual; women; transmission; antiretroviral treatment; black; Hispanic
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).
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.
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
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
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
PMCID: PMC2817715  PMID: 20161723
21.  Implementing family-focused HIV care and treatment: the first 2 years' experience of the mother-to-child transmission-plus program in Abidjan, Côte d'Ivoire 
To describe a family-focused approach to HIV care and treatment and report on the first two years’ experience of implementing the MTCT-Plus program in Abidjan, Côte d’Ivoire.
Program implementation
New effective models of care are being sought to provide successful strategies to deliver safe, efficient and appropriate HIV care and treatment in resource limited settings. The MTCT-Plus Initiative aims to engage pregnant and postpartum women identified as HIV-infected to initiate comprehensive HIV care and treatment for the woman and her family.
Main outcomes
Between August 2003 and August 2005, 605 HIV-infected pregnant or post-partum women and 582 HIV-exposed infants were enrolled. Amongst 568 male partners reported alive by enrolled women, 300 (52%) were aware of their wife’s HIV status and 169 (30%) have been tested for HIV. Amongst these partners, 88 (53%) were found to be HIV-infected and 69 (78%) were enrolled into the program. Overall only 10% of the women were enrolled together with their infected partner. On the other hand, a success of the program was also to involve a significant number of seronegative men (half of those who came for VCT) in the care of their families. Amongst 1,624 children <15 years reported alive by their mothers (excluding the last newborn infants of the most recent pregnancy systematically screened for HIV), only 146 (10.8%) were brought in for HIV testing, of whom 18 (12.3%) were found to be HIV-infected.
Lessons learned and challenges
The family-focused model of HIV care pays attention to the needs of families and household members. The program was successful in enrolling HIV women, their partners and infants in continuous follow-up. However engaging partners and family members of newly enrolled women into care involves numerous challenges outlined in the cascade of necessary events that must take place to achieve this goal. This involves the difficult issue of disclosure of HIV status by women to their partners and family members. Further efforts are required to understand barriers for families accessing HIV services as strategies to improve partner involvement and provide access to care for other children in the households are needed in this West African urban setting.
PMCID: PMC2793410  PMID: 19236666
Adolescent; Adult; Child; Child, Preschool; Cote d'Ivoire; epidemiology; Counseling; Family; Female; HIV Infections; epidemiology; prevention & control; transmission; HIV Seroprevalence; Humans; Infant; Infant, Newborn; Middle Aged; Patient Acceptance of Health Care; Pregnancy; Program Evaluation; Sexual Partners; Young Adult; Africa; antiretroviral; care; counseling; family approach; HIV; mother and partners
Atherosclerosis  2007;198(1):192-197.
Increased levels of postprandial triglycerides (TG) and remnant like particles (RLP) are associated with cardiovascular disease. We evaluated whether postprandial lipemia differed in HIV-positive patients with or without different antiretroviral regimens. A standardized high fat load was administered to 28 subjects: 11 HIV-positive subjects receiving protease inhibitors (PI), 10 HIV-positive subjects receiving non-nucleoside reverse transcriptase inhibitors (NNRTI) and 7 HIV-positive subjects not receiving highly active antiretroviral therapy, HAART (Naïve). Baseline TG levels and TG area under the curve (AUC) did not differ among the three groups. The postprandial TG concentration curves were similar in the NNRTI and Naïve groups, peaking at 3 to 5-hrs. Baseline RLP cholesterol was higher in the NNRTI group compared to other two groups (P=0.035). Both HAART groups (NNRTI and PI) had higher postprandial RLP cholesterol AUC than the Naïve group (P=0.024, ANOVA). In conclusion, during HIV conditions, HAART resulted in a pro-atherogenic pattern with accumulation of remnant lipoproteins.
PMCID: PMC2362066  PMID: 17996872
HIV; protease inhibitors-PI; non-nucleoside reverse transcriptase inhibitor-NNRTI; antiretroviral therapy; postprandial lipemia
23.  Determination of the Underlying Cause of Death in Three Multicenter International HIV Clinical Trials 
HIV clinical trials  2008;9(3):177-185.
Describe processes and challenges for an Endpoint Review Committee (ERC) in determining and adjudicating underlying causes of death in HIV clinical trials.
Three randomized HIV trials (two evaluating interleukin-2 and one treatment interruption) enrolled 11,593 persons from 36 countries during 1999–2008. Three ERC members independently reviewed each death report and supporting source documentation to assign underlying cause of death; differences of opinion were adjudicated.
Of 453 deaths reported through January 14, 2008, underlying causes were as follows: 10% AIDS-defining diseases, 21% non-AIDS malignancies, 9% cardiac diseases, 9% liver disease, 8% non-AIDS-defining infections, 5% suicides, 5% other traumatic events/accidents, 4% drug overdoses/acute intoxications, 11% other causes, and 18% unknown. Major reasons for unknown classification were inadequate clinical information or supporting documentation to determine cause of death. Half (51%) of deaths reviewed by the ERC required follow-up adjudication; consensus was eventually always reached.
ERCs can successfully provide blinded, independent, and systematic determinations of underlying cause of death in HIV clinical trials. Committees should include those familiar with AIDS and non-AIDS-defining diseases and have processes for adjudicating differences of opinion. Training for local investigators and procedure manuals should emphasize obtaining maximum possible documentation and follow-up information on all trial deaths.
PMCID: PMC2441601  PMID: 18547904
cause of death; endpoint review committees; clinical trials; HIV; mortality
25.  Antiretroviral Treatment and Prevention of Peripartum and Postnatal HIV Transmission in West Africa: Evaluation of a Two-Tiered Approach 
PLoS Medicine  2007;4(8):e257.
Highly active antiretroviral treatment (HAART) has only been recently recommended for HIV-infected pregnant women requiring treatment for their own health in resource-limited settings. However, there are few documented experiences from African countries. We evaluated the short-term (4 wk) and long-term (12 mo) effectiveness of a two-tiered strategy of prevention of mother-to-child transmission of HIV (PMTCT) in Africa: women meeting the eligibility criteria of the World Health Organization (WHO) received HAART, and women with less advanced HIV disease received short-course antiretroviral (scARV) PMTCT regimens.
Methods and Findings
The MTCT-Plus Initiative is a multi-country, family-centred HIV care and treatment program for pregnant and postpartum women and their families. Pregnant women enrolled in Abidjan, Côte d'Ivoire received either HAART for their own health or short-course antiretroviral (scARV) PMTCT regimens according to their clinical and immunological status. Plasma HIV-RNA viral load (VL) was measured to diagnose peripartum infection when infants were 4 wk of age, and HIV final status was documented either by rapid antibody testing when infants were aged ≥ 12 mo or by plasma VL earlier. The Kaplan-Meier method was used to estimate the rate of HIV transmission and HIV-free survival. Between August 2003 and June 2005, 107 women began HAART at a median of 30 wk of gestation, 102 of them with zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP) and they continued treatment postpartum; 143 other women received scARV for PMTCT, 103 of them with sc(ZDV+3TC) with single-dose NVP during labour. Most (75%) of the infants were breast-fed for a median of 5 mo. Overall, the rate of peripartum HIV transmission was 2.2% (95% confidence interval [CI] 0.3%–4.2%) and the cumulative rate at 12 mo was 5.7% (95% CI 2.5%–9.0%). The overall probability of infant death or infection with HIV was 4.3% (95% CI 1.7%–7.0%) at age week 4 wk and 11.7% (95% CI 7.5%–15.9%) at 12 mo.
This two-tiered strategy appears to be safe and highly effective for short- and long-term PMTCT in resource-constrained settings. These results indicate a further benefit of access to HAART for pregnant women who need treatment for their own health.
In an observational cohort study from Côte d'Ivoire, François Dabis and colleagues report on prevention of mother-to-child HIV transmission among women receiving antiretroviral therapy according to World Health Organization recommendations.
Editors' Summary
Effective treatments are available to prevent AIDS in people who are infected with HIV, but not everyone with HIV needs to take medication. Usually, anti-HIV medication is recommended only for those whose immune systems have been significantly affected by the virus, as evidenced by symptoms or by the results of a blood test, the CD4 lymphocyte (“T cell”) count. Treating HIV usually requires a combination of three or more medications. These combinations (called HAART) must be taken every day, can cause complications, and can be expensive.
Worldwide, more than half a million children became infected with HIV each year. Most of these children acquire HIV from their mothers during pregnancy or around the time of birth. If a pregnant woman with HIV takes HAART, her chances of passing HIV to the baby are greatly reduced, but the possible side effects of HAART on the baby are not known. Also, most transmission of HIV from mothers to babies occurs in poor countries where supplies of HAART are limited. For these reasons, World Health Organization (WHO) does not recommend that every pregnant woman receive HAART to prevent HIV transmission to the baby, unless the woman needs HAART for her own health (for example if her T cells are low or she has severe symptoms of HIV infection). For pregnant women with HIV who do not need to take HAART for their own health, less complicated treatments, involving a short course of one or two HIV drugs, can be used to reduce the risk of passing HIV to the baby.
Why Was This Study Done?
The WHO recommendations for HAART in pregnancy are based on the best available evidence, but it is important to know how well they work in actual practice. The authors of this study were providing HIV treatment to pregnant women with HIV in West Africa through an established clinic program in Abidjan, Côte d'Ivoire, and wanted to see how well the WHO recommendations for HAART or short-course treatments, depending on the mother's condition, were working to protect babies from HIV infection.
What Did the Researchers Do and Find?
The researchers studied 250 HIV-infected pregnant women who received HIV medications in the Abidjan program between mid-2003 and mid-2005. In accordance with WHO guidelines, 107 women began HAART for their own health during pregnancy, and 143 women did not qualify for HAART but received other short course treatments (scARV) to prevent HIV transmission to their babies. The authors monitored mothers and babies for treatment side effects and tested the babies for HIV infection up to age 1 y.
They found that HAART was relatively safe during pregnancy, although babies born to women on HAART were more likely (26.3%) to have low birth weight than babies born to women who received scARV (12.4%). Also, 7.5% of women on HAART developed side effects requiring a change in their medications. Combining the results from HAART and scART groups, the chance of HIV transmission around the time of birth was 2.2%, increasing to 5.7% at age 1 y. (Three-quarters of the infants were breast-fed; safe water for mixing formula was not reliably available.) The study found no difference in risk of HIV infection between babies whose mothers received HAART and those whose mothers received scARV according to guidelines.
What Do These Findings Mean?
These results support the safety and effectiveness of the WHO two-tiered approach for preventing mother-to-child transmission. This study was not designed to compare HAART to scART directly, because the women who received HAART were the ones with more advanced HIV infection, which might have affected their babies in many ways.
Compared to earlier pregnancy studies of HAART in rich countries, this study of the WHO approach in West Africa showed similar success in protecting infants from HIV infection around the time of birth. Unfortunately, because formula feeding was not generally available in resource-limited settings, protection declined over the first year of life with breast-feeding, but some protection remained.
This study confirms that close monitoring of pregnant women on HAART is necessary, so that drugs can be changed if side effects develop. The study does not tell us whether using scARV in pregnancy might change the virus in ways that would make it more difficult to treat the same women with HAART later if they needed it. The reason for low birth weight in some babies born to mothers on HAART is unclear. It may be because the women who needed HAART had more severe health problems from their HIV, or it may be a result of the HAART itself.
Additional Information.
Please access these Web sites via the online version of this summary at
World Health Organization has a page on prevention of mother-to-child transmission of HIV
“Women, Children, and HIV” is a resource site from the François Xavier Bagnoud Center and UCSF
The MTCT-Plus initiative at Columbia University supports the programs in Abidjan
PMCID: PMC1949842  PMID: 17713983

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