Manisha Ghate

High rates of syphilis among STI patients are contributing to the spread of HIV-1 in India

Background: Recent syphilis outbreaks have raised concern regarding the potential enhancement of HIV transmission. The incidence of syphilis and its association with HIV-1 infection rates among a cohort of sexually transmitted infection (STI) clinic attendees was investigated. Methods: 2732 HIV-1 seronegative patients attending three STI and one gynaecology clinic, were enrolled from 1993–2000 in an ongoing prospective cohort study of acute HIV-1 infection in Pune, India. At screening and quarterly follow up visits, participants underwent HIV-1 risk reduction counselling, risk behaviour assessment and HIV/STI screening that included testing for serological evidence of syphilis by RPR with TPHA confirmation. Patients with genital ulcers were screened with dark field microscopy. Results: Among 2324 participants who were HIV-1 and RPR seronegative at baseline, 172 participants were found to have clinical or laboratory evidence of syphilis during follow up (5.4 per 100 person years, 95% CI 4.8 to 6.5 per 100 person years). Independent predictors of syphilis acquisition based on a Cox proportional hazards model included age less than 20 years, lack of formal education, earlier calendar year of follow up, and recent HIV-1 infection. Based on a median follow up time of 11 months, the incidence of HIV-1 was 5.8 per 100 person years (95% CI 5.0 to 6.6 per 100 person years). Using a Cox proportional hazards model to adjust for known HIV risk factors, the adjusted hazard ratio of HIV-1 infection associated with incident syphilis was 4.44 (95% CI 2.96 to 6.65; p<0.001). Conclusions: A high incidence rate of syphilis was observed among STI clinic attendees. The elevated risk of HIV-1 infection that was observed among participants with incident syphilis supports the hypothesis that syphilis enhances the sexual transmission of HIV-1 and highlights the importance of early diagnosis and treatment of syphilis.

Correlates and Trend of HIV Prevalence Among Female Sex Workers Attending Sexually Transmitted Disease Clinics in Pune, India (1993–2002)

In India, substantial efforts have been made to increase awareness about HIV/AIDS among female sex workers (FSWs). We assessed the impact of awareness regarding safe sex in a cohort of FSWs by studying trends in HIV prevalence, sexually transmitted diseases (STDs), and risk behaviors measured from 1993 to 2002 in Pune, India. A total of 1359 FSWs attending 3 STD clinics were screened for HIV infection, and data on demographics, sexual behaviors, and past and current STDs were obtained. The overall HIV prevalence among FSWs was 54%. Not being married (adjusted odds ratio [AOR] = 1.74, 95% confidence interval [CI]: 1.17 to 2.59), being widowed (AOR = 2.10, 95% CI: 1.16 to 3.80), inconsistent condom use (AOR = 1.60, 95% CI: 1.02 to 2.50), clinical presence of genital ulcer disease (GUD; AOR = 1.66, 95% CI: 1.07 to 2.56), and genital warts (AOR = 4.70, 95% CI: 1.57 to 14.08) were independently associated with HIV infection among FSWs. The prevalence of HIV remained stable over 10 years (46% in 1993 and 50% in 2002; P = 0.80). The prevalence of GUD decreased over time (P < 0.001), whereas that of observed genital discharge remained stable. Reported consistent condom use as well as the proportion of FSWs who refused sexual contact without condoms increased over time (P < 0.001). These data collectively suggest that safe sex interventions have had a positive impact on FSWs in Pune, India.

Incidence of common opportunistic infections in HIV-infected individuals in Pune, India: analysis by stages of immunosuppression represented by CD4 counts

BACKGROUND Opportunistic infections (OIs) influence the morbidity and mortality due to HIV infections. Data from India on the incidence of OIs among HIV-infected individuals by stages of immunodeficiency are scarce. METHODS Between September 2002 and November 2004, HIV-infected individuals were enrolled in a prospective study in Pune. They were clinically and immunologically evaluated quarterly. Incidence rates of specific OIs were calculated. RESULTS Median CD4 counts in HIV-infected male and female patients at baseline were 197/mm(3) and 413/mm(3), respectively. Tuberculosis was the most common OI with an incidence of 15.4 (95% CI 12.2-19.2) per 100 person-years, followed by oral candidiasis 11.3 (95% CI 8.6-14.5), herpes zoster 10.1 (95% CI 7.6-13.1), and cryptococcal meningitis 1.7 (95% CI 0.8-3.1) per 100 person-years. Patients with baseline CD4 counts of <200/mm(3) were six times more likely to develop OIs compared to those with CD4 counts of >350/mm(3) (p<0.001). CONCLUSIONS The high incidence of commonly reported OIs in Indian HIV-infected individuals highlights the need for early screening and also the need to increase awareness in healthcare providers, in order to improve decisions regarding prophylaxis for prevention and appropriate therapeutic intervention. Emphasis needs to be given to the early diagnosis and management of tuberculosis in HIV-infected individuals.

Declining HIV incidence among patients attending sexually transmitted infection clinics in Pune India.

Objective:A recent report suggesting declining HIV transmission rates in southern India has been based on HIV seroprevalence data to estimate HIV incidence. We analyzed HIV incidence rates among 3 cohorts (male, female non-sex worker, female sex worker [FSW]) presenting to sexually transmitted infection (STI) clinics in Pune, India over 10 years. Methods:Between 1993 and 2002, consenting HIV-uninfected individuals were enrolled in a prospective study of the risks for HIV seroconversion. Standardized HIV incidence estimates were calculated separately for the 3 cohorts. Results:HIV acquisition risk declined by more than 70% for FSWs (P = 0.02) and men (P < 0.001) attending the STI clinics. There was no significant reduction in HIV incidence among women attending STI clinics (P = 0.74). The decline in HIV acquisition risk among male patients with STIs was associated with an increase in reported condom use with recent FSW contact and a decrease in genital ulcer disease. Conclusions:We report the first direct evidence for a decline in HIV incidence rates in FSWs and male patients with STIs over time. The lack of change in HIV infection risk among non-sex worker women highlights the need for additional targeted HIV prevention interventions.

Sexually transmitted infections and risk behaviors among transgender persons (Hijras) of Pune, India

BackgroundThe objectives of this cross-sectional study were to determine the prevalence of HIV and sexually transmitted infections (STI) in Hijras (self-identified transgenders of South Asia), study associated risk factors, and compare the prevalence with that in heterosexual men and men having sex with men (MSM) in Pune, India, between 1993 and 2002. MethodsAfter informed consent, individuals attending 3 STI clinics were administered a questionnaire regarding their demographic, socioeconomic, and sexual behaviors. Blood samples were collected for STI and HIV diagnosis. Bivariate and multivariate analyses were performed to determine the correlates of HIV infection. ResultsThe prevalence of HIV (45.2% in Hijras vs 20% in heterosexual men vs 18.9% in MSM, P < 0.0001) and warts (10.3% vs 4.6% vs 7.0%; P = 0.004) was higher in Hijras as compared with heterosexual men and MSM; whereas that of genital ulcer disease (15.3% vs 32.6% vs 21.5%; P < 0.0001) and discharge (5.4% vs 13.6% vs 9.0%; P < 0.0001) was lower. Hijras were more likely to have received money for sex and have an earlier sexual debut than the comparison groups. In multivariate analysis, receiving money for sex (adjusted odds ratio: 4.49; P < 0.04) and having genital ulcer disease (odds ratio: 3.87; P < 0.08) were independently associated with high HIV prevalence in Hijras. ConclusionsConsidering the high HIV and STI burden, it is important to review current prevention strategies and stress the need to engage Hijra community members through appropriate targeted intervention programs.

HIV-1 RNA shedding in the female genital tract is associated with reduced quantity of Lactobacilli in clinically asymptomatic HIV-positive women☆ , ☆☆

We quantified vaginal lactobacilli and determined their relationship with genital HIV-1 shedding and found a significant negative association between reduced quantity of lactobacilli and cervical HIV-1 viral load (r(2) = - 0.8900, P < 0.01), which may have implications of increased chances of sexual transmission of HIV-1 and genital infections.

Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India

Abstract The free antiretroviral therapy (ART) program in India has scaled up to register second largest number of people living with HIV/AIDS across the globe. To assess the effectiveness of current first-line regimen we estimated virological suppression on completion of 1 year of ART. The study describes the correlates of virological failure (VF) and multinucleoside reverse transcriptase inhibitor (NRTI) drug resistance mutations (DRMs). In this cross-sectional study conducted between June and August 2014, consecutive adults from 4 State sponsored ART clinics of western India were recruited for plasma viral load screening at 12 ± 2 months of ART initiation. Individuals with plasma viral load >1000 copies/mL were selected for HIV drug resistance (HIVDR) genotyping. Logistic regression analyses were performed to assess factors associated with VF and multi-NRTI resistance mutations. Criteria adopted for multi-NRTI resistance mutation were either presence of K65R or 3 or more thymidine analog mutations (TAMs) or presence of M184V along with 2 TAMs. Of the 844 study participants, virological suppression at 1 year was achieved in 87.7% of individuals. Factors significantly associated with VF (P < 0.005) were 12 months CD4 count of ⩽100 cells/&mgr;L (adjusted OR −7.11), low reported adherence (adjusted OR −4.44), and those living without any partner (adjusted OR −1.98). In patients with VF, the prevalence of non-nucleoside reverse transcriptase inhibitor (NNRTI) DRM (78.75%) were higher as compared to NRTI (58.75%). Multi-NRTI DRMs were present in 32.5% of sequences and were significantly associated with CD4 count of ⩽100 cells/&mgr;L at baseline (adjusted OR −13.00) and TDF-based failing regimen (adjusted OR −20.43). Additionally, low reported adherence was negatively associated with multi-NRTI resistance (adjusted OR −0.11, P = 0.015). K65R mutation was significantly associated with tenofovir (TDF)-based failing regimen (P < 0.001). The study supports early linkage of HIV-infected individuals to the program for ART initiation, adherence improvement, and introduction of viral load monitoring. With recent introduction of TDF-based regimen, the emergence of K65R needs to be monitored closely among HIV-1 subtype C-infected Indian population.

Near Full-Length Genomic Characterization of a Novel CRF 01_AE/C Recombinant from Western India

HIV is known for its genetic variability across the globe. The HIV epidemic in India is primarily driven by subtype C, although sporadic circulating and unique recombinant forms are also reported from a few metropolitan cities in which genotyping facilities are available. Here we report a novel CRF01_AE/C recombinant from a multicenter study on the effectiveness of antiretroviral therapy (ART), 12 months after its initiation. Our subject is a 32-year-old heterosexual female, a native of Pune city in western India. Identification and analyses of recombination breakpoints using jpHMM@Gobics and SimPlot bootscanning revealed six recombination breakpoints, indicating insertion of the CRF01_AE genome at three points in the backbone of subtype C. Both subtype C and CRF01_AE are commonly seen in the population at risk of heterosexual HIV transmission, thereby providing an opportunity for cocirculation and recombination. The emergence of a novel recombinant of CRF01_AE/C is indicative of the increasing genetic diversity of the HIV epidemic in India.

Indian Long-term Non-Progressors Show Broad ADCC Responses with Preferential Recognition of V3 Region of Envelope and a Region from Tat Protein

HIV-specific antibody-dependent cell cytotoxicity (ADCC) is likely to be important in governing protection from human immunodeficiency virus (HIV) and slowing disease progression. Little is known about the ADCC responses to HIV-1 subtype C. We characterized ADCC responses in HIV-1 subtype C-infected Indian subjects with slow disease progression and identified the dominant antigenic regions recognized by these antibodies. ADCC responses were measured in plasma from 34 long-term non-progressors (LTNPs), who were asymptomatic and maintained CD4 count above 500 cells/mm3 for the last 7 years in the absence of antiretroviral therapy (ART), and 58 ART naïve progressors with CD4 count <500 cells/mm3 against overlapping HIV-1 peptides using a flow cytometry-based antibody-dependent natural killer (NK) cell activation assay. The assay measured CD107a expression on NK cells as a marker of antibody-dependent NK cell activation and IFN-γ secretion by NK cells upon activation. The ADCC epitopes were mapped using the matrix of overlapping peptides. Indian LTNPs showed higher and broader ADCC responses compared to the progressors. The Env-C and Tat-specific ADCC responses were associated with lower plasma viral load, whereas the Env-C responses were also associated with higher CD4 counts. Five of 10 LTNP responders targeted epitopes in the V3 region (amino acids 288–330) of Env-C. Additionally, three Tat regions were targeted by ADCC antibodies from LTNPs. ADCC responses were associated with slow HIV progression in Indian subtype C-infected cohort. The frequently recognized peptides from the V3 loop of Env and the novel epitopes from Tat by the LTNPs warrants further study to understand the role of ADCC responses to these regions in control and prevention of HIV-1 infection.

Coping strategies of HIV-positive individuals and its correlation with quality of life in Pune, India

Quality of life including the domains of physical health and mental health are influenced by HIV infection. Coping strategies and their relationships with various domains of quality of life (QOL) were assessed among 97 HIV-infected individuals in Pune, India. Most of the infected individuals adopted emotion-focused strategies through cognitive reframing and acceptance of their HIV status. One-third adopted problem-focused coping and sought health care, scientific information and social support. Significant associations of coping strategies were observed with marital status and work and earning domains of the QOL questionnaire. Findings can help decide appropriate care and support strategies and psycho-social interventions for HIV-infected individuals.