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1.  Interactions of HIV, Other Sexually Transmitted Diseases, and Genital Tract Inflammation Facilitating Local Pathogen Transmission and Acquisition 
Despite several decades of clinical trials assessing the impact of etiological treatment of sexually transmitted diseases (STDs) to decrease HIV acquisition and transmission, almost all of these trials have not proven to be efficacious. Increasing evidence suggests that specific STD treatment alone may not be sufficient to alter the genital tract inflammatory milieu that is created by STDs. This paper examines the associations between STDs and HIV susceptibility and infectiousness, and considers the role of chronic and refractory inflammation to create an environment that potentiates HIV and STD transmission and acquisition by reviewing biological, observational, and clinical trial data.
doi:10.1111/j.1600-0897.2010.00942.x
PMCID: PMC3077541  PMID: 21214660
2.  Analysis of a non-structural gene reveals evidence of possible hepatitis C virus (HCV) compartmentalization 
Journal of medical virology  2012;84(2):242-252.
Viral diversity is a hallmark of hepatitis C virus (HCV) infection; however, only limited data are available regarding HCV variability in extrahepatic sites, and none have systematically compared diversity in non-structural and structural genomic regions. Therefore, HCV diversity in the NS5B and envelope 1 (E1) hypervariable region 1 (HVR1) genes was evaluated in matched sera and peripheral blood mononuclear cells (PBMCs) obtained from 13 HCV-infected women. Multiple clonal sequences were compared to evaluate quasispecies diversity and viral compartmentalization in PBMCs.
Genetic distances were higher for E1/HVR1 compared to NS5B in both the sera and PBMCs (p = 0.0511 and p = 0.0284). Genetic distances were higher in serum NS5B compared to PBMC NS5B (p = 0.0003); however, they were not different when comparing E1/HVR1 in sera to PBMCs. By phylogenetic analysis of NS5B, evidence of possible PBMC compartmentalization was observed for 1 woman, while statistical methods were consistent with PBMC compartmentalization for 6 women. Evidence of compartmentalization within a non-structural genomic region may suggest that viral adaptation to a unique extracellular microenvironment(s) may be required for efficient replication and could contribute to HCV persistence.
doi:10.1002/jmv.22269
PMCID: PMC3243959  PMID: 22170544
NS5B; HVR1; diversity; quasispecies; extrahepatic replication
3.  UNPROTECTED SEX, UNDERESTIMATED RISK, UNDIAGNOSED HIV AND SEXUALLY TRANSMITTED DISEASES AMONG MEN WHO HAVE SEX WITH MEN ACCESSING TESTING SERVICES IN A NEW ENGLAND BATHHOUSE 
American men who have sex with men (MSM) continue to have increased rates of HIV and STD. Between 2004 and 2010, 1155 MSM were screened for HIV and/or STD at a Providence, RI, bathhouse. The prevalence of HIV was 2.3%; syphilis, 2.0%; urethral gonorrhea, 0.1%; urethral Chlamydia, 1.3%; 2.2% of the men had hepatitis C antibodies. Although 43.2% of the men engaged in unprotected anal intercourse in the prior two months, the majority of the men thought that their behaviors did not put them at increased risk for HIV or STDs. Multivariate analyses found that men who engaged in unprotected anal intercourse were more likely to have had sex with unknown status or HIV-infected partners; have sex while under the influence of drugs; tended to find partners on the internet; and were more likely to have a primary male partner. Men who were newly diagnosed with HIV or syphilis tended to be over 30 years old; had sex with an HIV-infected partner; had a prior STD diagnosis; and met partners on the internet. For 10.5% of the men, their HIV testing in the bathhouse was the first time that they had ever been screened for HIV. Of 24 men who were newly diagnosed with HIV infection, only one was not successfully linked to care. These data suggest that offering HIV and STD screening in a bathhouse setting is successful in attracting MSM who were at increased risk for HIV and/or STD acquisition or transmission, and may help decrease spread.
doi:10.1097/QAI.0b013e31823bbecf
PMCID: PMC3261361  PMID: 22027871
Sexually transmitted infections; HIV; sexual risk; men having sex with men (MSM); bathhouse
4.  Chemoprophylaxis for HIV Prevention: New Opportunities and New Questions 
Growing data suggest that antiretrovirals can be used as an effective means of HIV prevention. This paper reviews the current status and future clinical prospects of utilizing antiretroviral chemoprophylaxis before and after high-risk HIV exposure to prevent HIV transmission. The discussion about using antiretrovirals as a means of primary HIV prevention has moved to the forefront of public health discourse because of a growing evidence base, the increased tolerability of the medications, the decreased cost, the ever expanding formulary, and the limitations of other approaches.
doi:10.1097/QAI.0b013e3181fbcb4c
PMCID: PMC3075435  PMID: 21406981
HIV; AIDS; primary prevention; ART; preexposure prophylaxis; postexposure prophylaxis; topical microbicides
5.  Antiretroviral Therapy for HIV Prevention: Present status and future prospects 
American journal of public health  2010;100(10):1867-1876.
doi:10.2105/AJPH.2009.184796
PMCID: PMC2936983  PMID: 20724682
HIV; AIDS; HAART; treatment; prevention
6.  Promising Prevention Approaches: Tenofovir Gel and Prophylactic use of Antiretroviral Medications 
Current HIV/AIDS reports  2011;8(4):241-248.
Thirty years into the global HIV epidemic, the need for effective prevention strategies remains critical. In July 2010, the CAPRISA-004 study demonstrated that topical administration of a gel containing the antiretroviral agent tenofovir decreased the risk of HIV acquisition among at-risk heterosexual women. Subsequently, the iPrEx study reported that prophylactic use of a daily oral tablet containing tenofovir and emtricitabine reduced the risk of HIV acquisition among high-risk men who have sex with men. These studies illustrate the promise of antiretroviral pre-exposure chemoprophylaxis (PrEP) as an innovative prevention approach. This review discusses the rationale for chemoprophylaxis, compares the advantages of topical and oral delivery, outlines recommended safety monitoring, offers principles to guide selection of antiretroviral agents, and highlights potential unintended consequences of PrEP use. If future studies confirm the safety and efficacy of tenofovir gel and oral PrEP, successful implementation of these strategies could significantly impact the HIV epidemic.
doi:10.1007/s11904-011-0094-4
PMCID: PMC3240840  PMID: 22002729
HIV; Primary Prevention; Chemoprevention; Anti-HIV Agents; Reverse Transcriptase Inhibitors; Gels; HIV infections/prevention & control; Clinical Trial; Unsafe Sex
7.  Social, Structural and Behavioral Drivers of Concurrent Partnerships among African American Men in Philadelphia 
AIDS care  2011;23(11):1392-1399.
African Americans face disproportionately higher risks of HIV infection. Concurrent sexual relationships, or sexual partnerships that overlap in time, are more common among African Americans than individuals of other races and may contribute to racial disparities in HIV infection. However, little is known about attitudes, norms and practices among individuals engaged in concurrent partnerships. Little is also known about the processes through which structural, behavioral and social factors influence concurrent sexual relationships. We recruited 24 heterosexual African American men involved in concurrent sexual relationships from a public health clinic in Philadelphia. We conducted in-depth interviews exploring these men's sexual practices; social norms and individual attitudes about concurrency; perceived sexual health risks with main and non-main partners; and the social, structural and behavioral factors contributing to concurrent sexual relationships. Twenty-two men reported having one main and one or more non-main partners; two reported having no main partners. Respondents generally perceived sexual relationships with non-main partners as riskier than relationships with main partners and used condoms far less frequently with main than non-main partners. Most participants commented that it is acceptable and often expected for men and women to engage in concurrent sexual relationships. Social factors influencing participants’ concurrent partnerships included being unmarried and trusting neither main nor non-main partners. Structural factors influencing concurrent partnerships included economic dependence on one or more women, incarceration, unstable housing, and unemployment. Several men commented that individual behavioral factors such as alcohol and cocaine use contributed to their concurrent sexual partnerships. Future research and interventions related to sexual concurrency should address social and structural factors in addition to conventional HIV risk-taking behaviors.
doi:10.1080/09540121.2011.565030
PMCID: PMC3202040  PMID: 21981345
8.  Men who have sex with men in India: A diverse population in need of medical attention 
A significant proportion of men engage in sexual relationships with other men which has direct health implications, but the unique health care needs of these patients are often ignored or overlooked. Moreover, due to a fear of stigmatization by the medical community, one of the more significant health risks for men who have sex with men (MSM) may be that they avoid routine or appropriate health care. Physicians and other providers can help overcome this barrier and improve the health care of MSM by keeping a non-judgmental attitude toward these patients, differentiating sexual behaviour from sexual identity, communicating with gender neutral terms, and maintaining awareness of how their own attitudes affect clinical judgment. The purpose of this article is to help contextualize health issues affecting MSM and provide a framework for physicians and other providers to deliver optimum and appropriate health care for men who have sex with men in India.
PMCID: PMC3516023  PMID: 23168696
HIV-1; MSM; primary care; sex behaviour; sexually transmitted infections
9.  Blood or Body Fluid Exposures and HIV Postexposure Prophylaxis Utilization among First Responders 
Objectives
To estimate the incidence of first-responder visits to emergency departments (EDs) for blood or body fluid exposures, elucidate any temporal patterns of these visits, and quantify human immunodeficiency virus (HIV) postexposure prophylaxis (PEP) utilization for these exposures.
Methods
This was a retrospective study of first responders presenting to Rhode Island EDs for blood or body fluid exposures from 1995 to 2001. Incidence rates for exposures with 95% confidence intervals (CIs) were estimated. Temporal trends for visits were modeled. Factors associated with HIV PEP utilization were identified using logistic regression. Odds ratios (ORs) with 95% CIs were estimated.
Results
The average incidence rate of ED visits for blood or body fluid exposures was 23.29 (20.07--26.52) ED visits per 100,000 ambulance runs. The incidence rose between 1995 and 1999 and then decreased. First-responder ED visits were lowest in October and highest in April and were lowest at 7 AM and highest at 7 PM. First responders presenting with a percutaneous or blood-to-mucous membrane exposure had a 4.13 (1.82--8.89) greater odds and those exposed to a known HIV-infected source had a 9.03 (1.59--51.26) greater odds of being offered HIV PEP. First responders presenting to a teaching hospital had a 2.21 (1.02--4.77) greater odds of being offered prophylaxis and a 4.20 (1.08--16.32) greater odds of accepting prophylaxis when it was offered.
Conclusions
First responders face a risk of blood or body fluid exposure that varies over the course of the day and the year. HIV PEP is more likely to be used if the exposures are percutaneous, or blood-to-mucous membrane, or if the source is known to be HIV-infected. Standardization of protocols across EDs for administering HIV prophylaxis appears to be needed.
doi:10.1080/10903120802471931
PMCID: PMC3440874  PMID: 19145518
emergency medical technicians; needlestick injuries; occupational exposures; blood; blood-borne pathogens; disease transmission
10.  Barriers to Routine HIV Testing Among Massachusetts Community Health Center Personnel 
Public Health Reports  2011;126(5):643-652.
Objectives
We assessed the extent to which Centers for Disease Control and Prevention (CDC) recommendations have influenced routine HIV testing among Massachusetts community health center (CHC) personnel, and identified specific barriers and facilitators to routine testing.
Methods
Thirty-one CHCs were enrolled in the study. We compared those that did and did not receive funding support from the federal Ryan White HIV/AIDS Program. An anonymous survey was administered to a maximum five personnel from each CHC, including a senior administrator, the medical director, and three medical providers. Overall, 137 participants completed the survey.
Results
Among all CHCs, 53% of administrators reported having implemented routine HIV testing at their CHCs; however, only 33% of medical directors/providers reported having implemented routine HIV testing in their practices (p<0.05). Among administrators, 60% of those from Ryan White-supported CHCs indicated that both they and their CHCs were aware of CDC's recommendations, compared with 27% of administrators from non-Ryan White-supported CHCs. The five most frequently reported barriers to the implementation of routine HIV testing were (1) constraints on providers' time (68%), (2) time required to administer counseling (65%), (3) time required to administer informed consent (52%), (4) lack of funding (35%), and (5) need for additional training (34%). In a multivariable logistic regression model, the provision of on-site HIV testing by nonmedical staff resulted in increased odds of conducting routine HIV testing (odds ratio [OR] = 9.84, 95% confidence interval [CI] 1.77, 54.70). However, the amount of time needed to administer informed consent was associated with decreased odds of providing routine testing (OR=0.21, 95% CI 0.05, 0.92).
Conclusions
Routine HIV testing is not currently being implemented uniformly among Massachusetts CHCs. Future efforts to increase implementation should address personnel concerns regarding time and staff availability.
PMCID: PMC3151181  PMID: 21886324
11.  Public Health Implications for Adequate Transitional Care for HIV-Infected Prisoners: Five Essential Components 
In the United States, 10 million inmates are released every year, and human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) prevalence is several-fold greater in criminal justice populations than in the community. Few effective linkage-to-the-community programs are currently available for prisoners infected with HIV. As a result, combination antiretroviral therapy (cART) is seldom continued after release, and virological and immunological outcomes worsen. Poor HIV treatment outcomes result from a myriad of obstacles that released prisoners face upon reentering the community, including homelessness, lack of medical insurance, relapse to drug and alcohol use, and mental illness. This article will focus on 5 distinct factors that contribute significantly to treatment outcomes for released prisoners infected with HIV and have profound individual and public health implications: (1) adaptation of case management services to facilitate linkage to care; (2) continuity of cART; (3) treatment of substance use disorders; (4) continuity of mental illness treatment; and (5) reducing HIV-associated risk-taking behaviors as part of secondary prevention.
doi:10.1093/cid/cir446
PMCID: PMC3156144  PMID: 21844030
12.  Suicidality, clinical depression, and anxiety disorders are highly prevalent in men who have sex with men in Mumbai, India: Findings from a community-recruited sample 
Psychology, health & medicine  2011;16(4):450-462.
In India men who have sex with men (MSM) are a stigmatized and hidden population, vulnerable to a variety of psychosocial and societal stressors. This population is also much more likely to be HIV-infected compared to the general population. However, little research exists about how psychosocial and societal stressors result in mental health problems. A confidential, quantitative mental-health interview was conducted among 150 MSM in Mumbai, India at The Humsafar Trust, the largest non-governmental organization serving MSM in India. The interview collected information on sociodemographics and assessed self-esteem, social support and DSM-IV psychiatric disorders using the Mini International Neuropsychiatric Interview (MINI). Participants' mean age was 25.1 years (SD=5.1); 21% were married to women. Forty-five percent reported current suicidal ideation, with 66% low risk, 19% moderate risk, and 15% high risk for suicide per MINI guidelines. Twenty-nine percent screened in for current major depression and 24% for any anxiety disorder. None of the respondents reported current treatment for any psychiatric disorder. In multivariable models controlling for age, education, income and sexual identity, participants reporting higher levels of self-esteem and greater levels of satisfaction with the social support they receive from family and friends were at lower risk of suicidality (self-esteem AOR=0.85, 95% CI: 0.78-0.93; social support AOR=0.76, 95% CI: 0.62-0.93) and major depression (self-esteem AOR=0.79, 95% CI: 0.71-0.89; social support AOR=0.68, 95% CI: 0.54-0.85). Those who reported greater social support satisfaction were also at lower risk of a clinical diagnosis of an anxiety disorder (AOR=0.80; 95% CI: 0.65-0.99). MSM in Mumbai have high rates of suicidal ideation, depression and anxiety. Programs to improve self-esteem and perceived social support may improve these mental health outcomes. Because they are also a high-risk group for HIV, MSM HIV prevention and treatment services may benefit from incorporating mental health services and referrals into their programs.
doi:10.1080/13548506.2011.554645
PMCID: PMC3136931  PMID: 21749242
Men who have sex with men (MSM); Mumbai; India; mental health; suicide; depression; anxiety
13.  Can Computer-Based Feedback Improve Emergency Department Patient Uptake of Rapid HIV Screening? 
Annals of emergency medicine  2011;58(1 Suppl 1):S114-9.e1-2.
Objective
We determine whether (1) an audiocomputer-delivered tailored feedback intervention increases emergency department (ED) patient uptake of opt-in, nontargeted rapid HIV screening; and (2) uptake is greater among patients who report more HIV risk and among those whose self-perceived HIV risk increases from baseline after completion of an HIV risk assessment.
Methods
ED patients aged 18 to 64 years were randomly assigned to receive either an assessment about reported and self-perceived HIV risk or an identical assessment plus feedback about their risk for having or acquiring an HIV infection, tailored according to their reported risk. All participants were offered a fingerstick rapid HIV test. Two-sample tests of binomial proportions were used to compare screening uptake by study arm. Multivariable logistic regression was used to assess the relationship of reported HIV risk and an increase in self-perceived HIV risk with uptake of HIV screening.
Results
Of the 566 participants, the median age was 29 years, 62.2% were women, and 66.9% previously had been tested for HIV. Uptake of HIV screening was similar in the intervention and no intervention arms (54.1% versus 55.5% [Δ =–0.01%; 95% confidence interval {CI} –0.09% to 0.07%]). An increase in self-perceived HIV risk predicted greater uptake of HIV screening for women (odds ratio 2.15; 95% CI 1.08 to 4.28) but not men (odds ratio 1.61; 95% CI 0.60 to 4.30). Uptake of HIV screening was not related to reported HIV risk.
Conclusion
Uptake of rapid HIV screening in the ED was not improved by this feedback intervention. Other methods need to be investigated to improve uptake of HIV screening by ED patients.
doi:10.1016/j.annemergmed.2011.03.035
PMCID: PMC3205940  PMID: 21684389
14.  Sexual risk behaviors among HIV-infected South Indian couples in the HAART era: implications for reproductive health and HIV care delivery 
AIDS care  2011;23(6):722-733.
The current study examines sexual behaviors among HIV-infected Indians in primary care, where access to highly active antiretroviral therapy (HAART) has recently increased. Between January to April 2008, we assessed the sexual behaviors of 247 HIV-infected South Indians in care. Multivariable logistic regression models were used to determine predictors of being in a HIV-seroconcordant primary relationship, being sexually active, and reporting unprotected sex. Over three-fourths (80%) of participants were HAART-experienced. Among the 58% of participants who were currently in a seroconcordant relationship, one-third were serodiscordant when first tested for HIV. Approximately two-thirds (63.2%) of participants were sexually active; 9.0% reported unprotected sex. In the multivariable analyses, participants who were in a seroconcordant primary relationship were more likely to have children, use alcohol, report unprotected sex, and have been enrolled in care for >12 months. Sexually active participants were more likely to be on HAART, have a prior tuberculosis diagnosis, test Herpes simplex type 2 antibody seropositive, and have low general health perceptions. Participants who reported unprotected sex were more likely to be in a seroconcordant relationship, be childless, want to have a child, and use alcohol. We did not document an association between HAART and unprotected sex. Among HIV-infected Indians in primary care, predictors of unprotected sex included alcohol use and desire for children. Prevention interventions for Indian couples should integrate reproductive health and alcohol use counseling at entry into care.
doi:10.1080/09540121.2010.525616
PMCID: PMC3095699  PMID: 21293990
HIV; AIDS; sexual behavior; HAART; India
16.  Low Perceived Risk and High HIV Prevalence Among a Predominantly African American Population Participating in Philadelphia's Rapid HIV Testing Program 
AIDS Patient Care and STDs  2011;25(4):229-235.
Abstract
African Americans are disproportionately infected with HIV/AIDS. Despite Centers for Disease Control and Prevention (CDC) guidelines recommending routine opt-out testing for HIV, most HIV screening is based on self-perceived HIV risks. Philadelphia launched a rapid HIV testing program in seven public health clinics in 2007. The program provides free rapid oral HIV tests to all patients presenting for health services who provide informed consent. We analyzed demographic, risk behavior, and HIV serostatus data collected during the program between September 2007 and January 2009. We used multivariable logistic regression to estimate the association between behavioral and demographic factors and newly diagnosed HIV infection. Of the 5871 individuals testing for HIV, 47% were male, 88% were African American, and the mean age was 34.7 years. Overall HIV prevalence was 1.1%. All positive tests represented new HIV diagnoses, and 72% of individuals reported testing previously. Approximately 90% of HIV-positive individuals and 92% of individuals with more than five recent sex partners never, or only sometimes, used condoms. Two thirds of individuals testing positive and 87% of individuals testing negative assessed their own HIV risk as zero or low. Individuals reporting cocaine use and ever having a same sex partner both had 2.6 times greater odds of testing positive. Condom use in this population was low, even among high-risk individuals. Philadelphia's program successfully provided HIV testing to many underserved African Americans who underestimate their HIV risk. Our results nevertheless suggest greater efforts are needed to encourage more individuals to undergo HIV testing in Philadelphia, particularly those who have never tested.
doi:10.1089/apc.2010.0313
PMCID: PMC3068868  PMID: 21406004
17.  Lack of Association of Herpes Simplex Virus Type 2 Seropositivity With the Progression of HIV Infection in the HERS Cohort 
American Journal of Epidemiology  2011;173(7):837-844.
Many studies have chronicled the “epidemiologic synergy” between human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV-2). HIV adversely affects the natural history of HSV-2 and results in more frequent and severe HSV-2 reactivation. Few longitudinal studies, however, have examined whether HSV-2 is associated with increased HIV plasma viral loads or decreased CD4 counts. The authors estimated the effect of HSV-2 seropositivity on HIV RNA viral load and on CD4 count over time among 777 HIV-seropositive US women not receiving suppressive HSV-2 therapy in the HIV Epidemiology Research Study (1993–2000). Linear mixed models were used to assess the effect of HSV-2 on log HIV viral load and CD4 count/mm3 prior to widespread initiation of highly active antiretroviral therapy. Coinfection with HSV-2 was not associated with HIV RNA plasma viral loads during study follow-up. There was a statistically significant association between HSV-2 seropositivity and CD4 count over time, but this difference was small and counterintuitive at an increase of 8 cells/mm3 (95% confidence interval: 2, 14) per year among HSV-2-seropositive women compared with HSV-2-seronegative women. These data do not support a clinically meaningful effect of baseline HSV-2 seropositivity on the trajectories of HIV plasma viral loads or CD4 counts.
doi:10.1093/aje/kwq432
PMCID: PMC3105280  PMID: 21372062
CD4 lymphocyte count; herpes simplex; herpesvirus 2, human; HIV; viral load
18.  Incident Hepatitis C Virus Infection among US HIV-Infected Men Enrolled in Clinical Trials 
HCV incidence from 1996-2008 among HIV-infected men in U.S. HIV therapeutic trials was 0.51 per 100 person-years. Incident HCV occurred primarily through non-parenteral means; 75% of seroconverters reported no drug injection. At-risk HIV-infected persons should have access to HCV surveillance
Background. Outbreaks of sexually transmitted hepatitis C virus (HCV) infection have been reported among human immunodeficiency virus (HIV)–infected men who have sex with men in Europe, Australia, and New York. Whether this is occurring across the United States is unknown.
Methods. We determined incidence of HCV infection during 1996–2008 among male participants of the AIDS Clinical Trial Group Longitudinal Linked Randomized Trials cohort, a long-term study of HIV-infected persons randomized into selected US-based clinical trials. We evaluated associations with self-reported injection drug use (IDU), time-varying CD4+ cell count, and HIV RNA level with use of multivariate Poisson regression. No sexual or non-IDU risk factor data was available.
Results. A total of 1830 men had an initial negative HCV antibody test result and at least 1 subsequent HCV antibody test result, contributing >7000 person-years. At the time of the initial negative HCV antibody test result, 94% of men were receiving highly active antiretroviral therapy (HAART) and 6% reported current or prior IDU. Thirty-six seroconverted, with overall incidence of .51 cases per 100 person-years (95% confidence interval, .36–.70). Mean age at seroconversion was 46 years. Seroconversion was associated with IDU (25% of seroconverters reported IDU history vs 5% of nonseroconverters; P < .001), whereas 75% (n = 27) of seroconverters reported no IDU (incidence, 2.67 cases per 100 person-years among IDUs, .40 cases per 100 person-years among non-IDUs). Seroconversion was associated with HIV RNA level >400 copies/mL (44% at time of antibody positivity vs 21% at time of last negative antibody test result; P = .02) but not with CD4+ cell count.
Conclusions. Incident HCV infection occurs in HIV-infected men involved in US HIV therapeutic trials, primarily through nonparenteral means, despite engagement in care and HAART. HCV antibody development was not related to immune status but was associated with inadequate HIV suppression. At-risk HIV-infected persons should have access to HCV surveillance.
doi:10.1093/cid/ciq201
PMCID: PMC3106260  PMID: 21282184
19.  Safety, Tolerability, and efficacy of second-line generic protease inhibitor containing HAART after first-line failure among South Indian HIV-infected patients 
Introduction
We describe the safety, tolerability, and efficacy of protease inhibitor (PI) containing HAART among patients switching from non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART) from a clinical setting in South India.
Methods
We assessed a prospective cohort of 91 HIV-infected patients with at least 12 months of clinical follow-up on second line ritonvair boosted PI-based therapy between August 2003 and December 2008.
Results
Over three-fourths of patients met the WHO criteria for immunological failure at the time of switch. The median time to switch was 758 days. Patients demonstrated consistent increases in their CD4 cell counts during the first 12 months, by which time the median CD4 cell count was 322 cells/ul. The most common adverse events within the first year after switch were nausea (14.8%), lipodystrophy (10.4%), and peripheral neuropathy (7.0%). Patients switching to ATV-based regimens compared to those switching to IDV-based regimens had similar immunological and clinical outcomes.
Conclusions
Given the therapeutic success of utilizing second-line PI-containing HAART after experiencing treatment failure, further efforts must be taken to expand access to second-line HAART so that more patients can benefit from these drugs.
doi:10.1177/1545109710382780
PMCID: PMC3128549  PMID: 21266320
HIV; AIDS; India; HAART; second-line therapy; protease inhibitors
20.  HIV Mono-infection Is Associated With FIB-4 – A Noninvasive Index of Liver Fibrosis – in Women 
Predictors of liver fibrosis were evaluated in women using a noninvasive index (FIB-4). HIV RNA levels were associated with increased FIB-4 in the absence of viral hepatitis, alcohol use, or antiretroviral therapy. These data complement evidence suggesting a potential relationship between HIV infection and hepatic fibrosis.
Background. FIB-4 represents a noninvasive, composite index that is a validated measure of hepatic fibrosis, which is an important indicator of liver disease. To date, there are limited data regarding hepatic fibrosis in women.
Methods. FIB-4 was evaluated in a cohort of 1227 women, and associations were evaluated in univariate and multivariate regression models among 4 groups of subjects classified by their human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection status.
Results. The median FIB-4 scores were 0.60 in HIV-/HCV- women, 0.83 in HIV-/HCV+ women, 0.86 in HIV+/HCV- women, and 1.30 in HIV+/HCV+ women. In the HIV/HCV co-infected group, multivariate analysis showed that CD4+ cell count and albumin level were negatively associated with FIB-4 (P <.0001), whereas antiretroviral therapy (ART) was positively associated with FIB-4 score (P =.0008). For the HIV mono-infected group, multivariate analysis showed that CD4+ cell count (P <.0001) and albumin level (P =.0019) were negatively correlated with FIB-4 score, ART was positively associated with FIB-4 score (P =.0008), and plasma HIV RNA level was marginally associated with FIB-4 score (P =.080). In 72 HIV mono-infected women who were also hepatitis B surface antigen negative, ART naive, and reported no recent alcohol intake, plasma HIV RNA level was associated with increased FIB-4 score (P =.030).
Conclusions. HIV RNA level was associated with increased FIB-4 score in the absence of hepatitis B, hepatitis C, ART, or alcohol use, suggesting a potential relationship between HIV infection and hepatic fibrosis in vivo. A better understanding of the various demographic and virologic variables that contribute to hepatic fibrosis may lead to more effective treatment of HIV infection and its co-morbid conditions.
doi:10.1093/cid/ciq199
PMCID: PMC3106241  PMID: 21248367
21.  Pharmacy Adherence Measures to Assess Adherence to Antiretroviral Therapy: Review of the Literature and Implications for Treatment Monitoring 
Prescription or pill-based methods for estimating adherence to antiretroviral therapy (ART), pharmacy adherence measures (PAMs), are objective estimates calculated from routinely collected pharmacy data. We conducted a literature review to evaluate PAMs, including their association with virological and other clinical outcomes, their efficacy compared with other adherence measures, and factors to consider when selecting a PAM to monitor adherence. PAMs were classified into 3 categories: medication possession ratio (MPR), pill count (PC), and pill pick-up (PPU). Data exist to recommend PAMs over self-reported adherence. PAMs consistently predicted patient outcomes, but additional studies are needed to determine the most predictive PAM parameters. Current evidence suggests that shorter duration of adherence assessment (≤6 months) and use of PAMs to predict future outcomes may be less accurate. PAMs which incorporate the number of days for which ART was prescribed without the counting of remnant pills, are reasonable minimum-resource methods to assess adherence to ART.
doi:10.1093/cid/ciq167
PMCID: PMC3060901  PMID: 21245156
22.  Predictors of Nonadherence to Highly Active Antiretroviral Therapy Among HIV-Infected South Indians in Clinical Care: Implications for Developing Adherence Interventions in Resource-Limited Settings 
AIDS Patient Care and STDs  2010;24(12):795-803.
Abstract
In light of the increasing availability of generic highly active antiretroviral therapy (HAART) in India, further data are needed to examine variables associated with HAART nonadherence among HIV-infected Indians in clinical care. We conducted a cross-sectional analysis of 198 HIV-infected South Indian men and women between January and April 2008 receiving first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART. Nonadherence was defined as taking less than 95% of HAART doses in the last 1 month, and was examined using multivariable logistic regression models. Half of the participants reported less than 95% adherence to HAART, and 50% had been on HAART for more than 24 months. The median CD4 cell count was 435 cells per microliter. An increased odds of nonadherence was found for participants with current CD4 cell counts greater than 500 cells per microliter (adjusted odds ratio [AOR]: 2.22 [95% confidence interval {CI}: 1.04–4.75]; p = 0.038), who were on HAART for more than 24 months (AOR: 3.07 [95% CI: 1.35–7.01]; p = 0.007), who reported alcohol use (AOR: 5.68 [95%CI: 2.10-15.32]; p = 0.001), who had low general health perceptions (AOR: 3.58 [95%CI: 1.20-10.66]; p = 0.021), and who had high distress (AOR: 3.32 [95%CI: 1.19-9.26]; p = 0.022). This study documents several modifiable risk factors for nonadherence in a clinic population of HIV-infected Indians with substantial HAART experience. Further targeted culturally specific interventions are needed that address barriers to optimal adherence.
doi:10.1089/apc.2010.0153
PMCID: PMC3011993  PMID: 21091232
23.  Low-cost assays for monitoring HIV infected individuals in resource-limited settings 
Use of a combination of CD4 counts and HIV viral load testing in the management of antiretroviral therapy (ART) provides higher prognostic estimation of the risk of disease progression than does the use of either test alone. The standard methods to monitor HIV infection are flow cytometry based for CD4+ T cell count and molecular assays to quantify plasma viral load of HIV. Commercial assays have been routinely used in developed countries to monitor ART. However, these assays require expensive equipment and reagents, well trained operators, and established laboratory infrastructure. These requirements restrict their use in resource-limited settings where people are most afflicted with the HIV-1 epidemic. With the advent of low-cost and/or low-tech alternatives, the possibility of implementing CD4 count and viral load testing in the management of ART in resource-limited settings is increasing. However, an appropriate validation should have been done before putting them to use for patient testing.
doi:10.4103/0971-5916.92628
PMCID: PMC3284092  PMID: 22310816
CD4 count; HIV monitoring; low-cost assays; plasma viral load; resource-limited settings
24.  HIV in Indian MSM: Reasons for a concentrated epidemic & strategies for prevention 
Men who have sex with men (MSM) in India are disproportionately likely to be HIV-infected, and face distinct psychosocial challenges. Understanding the unique socio-cultural issues of MSM in India and how they relate to HIV risk could maximize the utility of future prevention efforts. This review discusses: (i) the importance of addressing co-occurring mental health issues, such as depression, which may interfere with MSM's ability to benefit from traditional risk reduction counselling, (ii) reducing HIV-related stigma among health providers, policymakers and the lay public, and (iii) the role for non-governmental organizations that work with the community to play in providing culturally relevant HIV prevention programmes for MSM.
doi:10.4103/0971-5916.92637
PMCID: PMC3284100  PMID: 22310824
HIV; India; men who have sex with men; MSM; mental health; stigma
25.  Cost-Effectiveness of Tenofovir as First-Line Antiretroviral Therapy in India 
Background
World Health Organization guidelines for antiretroviral treatment (ART) in resource-limited settings recommend either stavudine or tenofovir as part of initial therapy. We evaluated the clinical outcomes and cost-effectiveness of first-line ART using tenofovir in India, compared to current practice using stavudine or zidovudine.
Methods
We used a state-transition model of HIV disease to examine strategies using different nucleoside reverse transcriptase inhibitors, combined with lamivudine and nevirapine, compared to no ART: 1) stavudine; 2) stavudine, with substitution by zidovudine after six months; 3) zidovudine; 4) tenofovir. Data were from the Y.R. Gaitonde Centre for AIDS Research and Education in Chennai, India and published studies.
Results
Discounted mean per person survival was 36.9 months (40.1 months undiscounted) with no ART, 115.5 months (145.3) with stavudine-containing ART, 115.6 months (145.5) with stavudine and six-month zidovudine substitution, 115.7 months (145.6) with zidovudine-containing ART, and 125.9 months (162.2) with initial tenofovir. Discounted lifetime medical costs were $610 with no ART and ranged from $5,560 with stavudine-containing ART to $5,720 with zidovudine-containing ART. Initial tenofovir had an incremental cost-effectiveness ratio of $670/year of life saved compared to no ART and was more economically efficient than the other regimens. Results were most sensitive to variations in the costs of first-line tenofovir, access to additional ART after failure, mean initial CD4 count, and quality of life adjustment.
Conclusions
Using tenofovir as part of first-line ART in India will improve survival, is cost-effective by international standards, and should be considered for initial therapy for HIV-infected patients in India.
doi:10.1086/649884
PMCID: PMC3225050  PMID: 20043752
HIV; cost-effective; India; antiretroviral treatment; resource-limited settings

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