Kartik K. Venkatesh

Who gets tested for HIV in a South African urban township? Implications for test and treat and gender-based prevention interventions.

Background:With increasing calls for linking HIV-infected individuals to treatment and care via expanded testing, we examined sociodemographic and behavioral characteristics associated with HIV testing among men and women in Soweto, South Africa. Methods:We conducted a cross-sectional household survey involving 1539 men and 1877 women as part of the community-randomized prevention trial Project ACCEPT/HPTN043 between July 2007 to October 2007. Multivariable logistic regression models, stratified by sex, assessed factors associated with HIV testing and then repeated testing. Results:Most women (64.8%) and 28.9% of men reported ever having been tested for HIV, among whom 57.9% reported repeated HIV testing. In multivariable analyses, youth and students had a lower odds of HIV testing. Men and women who had conversations about HIV/AIDS with increasing frequency and who had heard about antiretroviral therapy were more likely to report HIV testing, and repeated testing. Men who had ≥12 years of education and who were of high socioeconomic status, and women who were married, who were of low socioeconomic status, and who had children under their care had a higher odds of HIV testing. Women, older individuals, those with higher levels of education, married individuals, and those with children under their care had a higher odds of reporting repeated HIV testing. Uptake of HIV testing was not associated with condom use, having multiple sex partners, and HIV-related stigma. Conclusions:Given the low uptake of HIV testing among men and youth, further targeted interventions could facilitate a test and treat strategy among urban South Africans.

Interactions of HIV, Other Sexually Transmitted Diseases, and Genital Tract Inflammation Facilitating Local Pathogen Transmission and Acquisition

Citation 
Mayer KH, Venkatesh KK. Interactions of HIV, other sexually transmitted diseases, and genital tract inflammation facilitating local pathogen transmission and acquisition. Am J Reprod Immunol 2011; 65: 308–316

High Frequency of Clinically Significant Mutations after First-Line Generic Highly Active Antiretroviral Therapy Failure: Implications for Second-Line Options in Resource-Limited Settings

Continuation of failed highly active antiretroviral therapy regimens can lead to the accumulation of mutations that may limit options for second-line treatment. We studied the pattern of drug resistance mutations among 138 Indian patients who experienced failure of nonnucleotide reverse-transcriptase-containing first-line highly active antiretroviral therapy. This study demonstrates a high frequency of drug resistance mutations in human immunodeficiency virus-infected Indians who experience immunologic treatment failure and suggests the need for viral load monitoring.

Antiretroviral Therapy as HIV Prevention: Status and Prospects

As antiretroviral treatment of HIV infection has become increasingly accessible, attention has focused on whether these drugs can used for prevention because of increased tolerability of newer medications, decreased cost, and the limitations of other approaches. We review the status of antiretroviral HIV prevention, including chemoprophylaxis, as well as the effects of treatment of infected individuals on prevention. It is possible that the life-saving agents that have transformed the natural history of AIDS can be a critical component of HIV prevention efforts, but their ultimate role in affecting HIV transmission dynamics remains to be defined.

Decreased sexual risk behavior in the era of HAART among HIV-infected urban and rural South Africans attending primary care clinics.

Objective:In light of increasing access to HAART in sub-Saharan Africa, we conducted a longitudinal study to assess the impact of HAART on sexual risk behaviors among HIV-infected South Africans in urban and rural primary care clinics. Design:Prospective observational cohort. Methods:We conducted a cohort study at rural and urban primary care HIV clinics in South Africa consisting of 1544 men and 4719 women enrolled from 2003 to 2010, representing 19703 clinic visits. The primary outcomes were being sexually active, unprotected sex, and more than one sex partner and were evaluated at 6 monthly intervals. Generalized estimated equations assessed the impact of HAART on sexual risk behaviors. Results:Among 6263 HIV-infected men and women, over a third (37.2%) initiated HAART during study follow-up. In comparison to pre-HAART follow-up, visits while receiving HAART were associated with a decrease in those reporting being sexually active [adjusted odds ratio: 0.86 (95% confidence interval: 0.78–0.95)]. Unprotected sex and having more than one sex partner were reduced at visits following HAART initiation compared to pre-HAART visits [adjusted odds ratio: 0.40 (95% confidence interval: 0.34–0.46) and adjusted odds ratio: 0.20 (95% confidence interval: 0.14–0.29), respectively]. Conclusion:Sexual risk behavior significantly decreased following HAART initiation among HIV-infected South African men and women in primary care programs. The further expansion of antiretroviral treatment programs could enhance HIV prevention efforts in Africa.

Spectrum of adverse events after generic HAART in southern Indian HIV-infected patients.

To determine the incidence of clinically significant adverse events after long-term, fixed-dose, generic highly active antiretroviral therapy (HAART) use among HIV-infected individuals in South India, we examined the experiences of 3154 HIV-infected individuals who received a minimum of 3 months of generic HAART between February 1996 and December 2006 at a tertiary HIV care referral center in South India. The most common regimens were 3TC + d4T + nevirapine (NVP) (54.8%), zidovudine (AZT) + 3TC + NVP (14.5%), 3TC + d4T + efavirenz (EFV) (20.1%), and AZT + 3TC + EFV (5.4%). The most common adverse events and median CD4 at time of event were rash (15.2%; CD4, 285 cells/microL) and peripheral neuropathy (9.0% and 348 cells/microL). Clinically significant anemia (hemoglobin <7 g/dL) was observed in 5.4% of patients (CD4, 165 cells/microL) and hepatitis (clinical jaundice with alanine aminotransferase > 5 times upper limits of normal) in 3.5% of patients (CD4, 260 cells/microL). Women were significantly more likely to experience lactic acidosis, while men were significantly more likely to experience immune reconstitution syndrome (p < 0.05). Among the patients with 1 year of follow-up, NVP therapy was significantly associated with developing rash and d4T therapy with developing peripheral neuropathy (p < 0.05). Anemia and hepatitis often occur within 12 weeks of initiating generic HAART. Frequent and early monitoring for these toxicities is warranted in developing countries where generic HAART is increasingly available.

Is expanded HIV treatment preventing new infections? Impact of antiretroviral therapy on sexual risk behaviors in the developing world.

There have been dramatic increases in access to antiretroviral therapy (ART) across the developing world, and growing public health attention has focused on the possibility of utilizing ART as a means of slowing the global HIV epidemic. The preventive impact of ART will likely depend on decreasing levels of sexual risk behaviors following treatment initiation. The current review study examines the impact of wider access to ART on sexual risk behaviors among HIV-infected individuals in the developing world. The observational studies to date demonstrate that ART is associated with a significant reduction in unprotected sex following treatment initiation. Although data on the impact of ART on possible risk compensation are rapidly expanding across the developing world, more evidence is still needed before we can safely conclude expanded treatment will result in durable decreases in sexual risk behaviors.

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

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.

Safety, Tolerability and Effectiveness of Generic HAART in HIV-Infected Children in South India

HIV-infected children in resource-limited settings are increasingly gaining greater access to highly active antiretroviral therapy (HAART) but documented longitudinal data remains limited. We aimed to study the clinical and immunological outcomes among 67 South Indian HIV-infected children with >18 months of follow-up on HAART at a tertiary HIV care program. The median CD4 cell count at enrolment was 290 cells microl(-1) and at treatment initiation was 225 cells microl(-1). Patients demonstrated a significant rise in their CD4 cell counts between treatment initiation and after 6 months (701 cells microll(-1); p = 0.007), 12 months (741 cells microl(-1); p = 0.037), and 18 months of therapy (718 cells microl(-1); p = 0.005). The most common adverse events to therapy were nausea (20.9%) and rash (25.4%). Over one-fifth of patients (25.4%) substituted therapy due to toxicities and 19.4% of patients switched to second-line protease inhibitor-containing regimens. In this South Indian pediatric cohort, generic HAART was safe, effective and relatively well tolerated.

Gender-Based Differences in Treatment and Outcome among HIV Patients in South India

OBJECTIVE To describe gender-based differences in disease progression, treatment, and outcome among patients receiving highly active antiretroviral therapy (HAART) in South India. METHODS Therapy-naïve patients initiating HAART between February 1996 and June 2006 at a tertiary HIV referral center in Chennai, South India, were analyzed using the YRG CARE HIV Observational Database. Patients with 1 year of follow-up after initiating HAART were examined to investigate immunological and clinical outcomes, including the development of adverse events to therapy and opportunistic infections. RESULTS All previously therapy-naïve patients who initiated HAART with at least 1 year of follow-up (n = 1972) were analyzed. At enrollment into care, women had higher CD4 counts, lower hemoglobin, and higher body mass index (BMI) than their male counterparts (p < 0.05). At the time of initiating therapy, women had higher CD4 counts and lower hemoglobin (p < 0.05); women continued to have higher CD4 counts at 12 months (p < 0.05). After 1 year following HAART initiation, significantly more men developed tuberculosis and Pneumocystis jiroveci pneumonia (p < 0.05), more women experienced lactic acidosis and nausea, and more men developed immune reconstitution syndrome (p < 0.05). CONCLUSIONS Significant physiological, immunological, and clinical differences exist between men and women initiating HAART in a resource-limited setting in South India. Future studies should examine whether clinical management strategies should be different for men and women in resource-limited settings.