Raman Gangakhedkar

Male circumcision and risk of HIV-1 and other sexually transmitted infections in India

Circumcised men have a lower risk of HIV-1 infection than uncircumcised men. Laboratory findings suggest that the foreskin is enriched with HIV-1 target cells. However, some data suggest that circumcision could simply be a marker for low-risk behaviours. In a prospective study of 2298 HIV-uninfected men attending sexually transmitted infection clinics in India, we noted that circumcision was strongly protective against HIV-1 infection (adjusted relative risk 0.15; 95% CI 0.04-0.62; p=0.0089); however, we noted no protective effect against herpes simplex virus type 2, syphilis, or gonorrhoea. The specificity of this relation suggests a biological rather than behavioural explanation for the protective effect of male circumcision against HIV-1.

The etiology of genital ulcer disease by multiplex polymerase chain reaction and relationship to HIV infection among patients attending sexually transmitted disease clinics in Pune, India

OBJECTIVES To determine the etiology of genital ulcer disease (GUD) among patients attending sexually transmitted disease (STD) clinics in Pune, India, and to examine the relationship to HIV infection and compare the clinical diagnosis of GUD with the results of a multiplex polymerase chain reaction (M-PCR) assay for Treponema pallidum, herpes simplex virus (HSV), and Hemophilus ducreyi infection. METHODS Between June 20, 1994, and September 26, 1994, 302 patients with a genital ulcer were evaluated. Clinical etiology of GUD was based on physical appearance and microbiologic evaluations which included darkfield microscopy and serology for syphilis. Swabs of each genital ulcer were tested for HSV antigen by enzyme immunoassay (Herpchek; Dupont, Wilmington, DE) and processed in a multiplex PCR assay (M-PCR; Roche, Branchburg, NJ) for simultaneous detection of HSV, Treponema pallidum, and Hemophilus ducreyi. RESULTS Two hundred seventy-seven men and 25 women with a median age of 25 were evaluated. The seroprevalence of HIV was 22.2%. The etiology of GUD as determined by M-PCR was HSV (26%), H. ducreyi (23%), T. pallidum (10%), and multiple infections (7%); no etiology was identified in 34%. HIV seroprevalence was higher among those patients positive for HSV compared with other etiologies (OR = 2.1, CI: 1.2-3.7; p = 0.01). When compared with M-PCR, the Herpchek test was 68.5% sensitive and 99.5% specific. Darkfield detection for T. pallidum was 39% sensitive and 82% specific, in contrast to rapid plasma reagin and fluorescent treponemal antibody absorption test, which was 66% sensitive and 90% specific. Clinical diagnosis alone or in combination with basic laboratory tests showed poor agreement with M-PCR.

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.

Effect of α-thalassemia on sickle-cell anemia linked to the Arab-Indian haplotype in India

Two population groups from Western India with a high prevalence of the βs gene, one tribal (Valsad) and the other nontribal (Nagpur), were studied. The βs gene frequency in both populations was similar (0.22 vs. 0.23), but not the clinical expression of sickle‐cell anemia (SS): the sickle homozygotes in the tribal group appeared to have a mild clinical course, whereas the majority in the nontribal group exhibited a more severe clinical phenotype. Both tribal and nontribal SS patients had a similarly high mean hemoglobin (Hb)F expression (18.5% vs. 15.5%) and a high number of F cells (72.3% vs. 66.6%). DNA analysis of the β‐globin gene cluster region revealed that in these two populations, this portion of DNA was identical with and corresponded to the typical Arab‐Indian haplotype. Nevertheless, in heterozygotes, the mean βs expression was lower (27.9%) in the tribal as compared to the nontribal group (35.5%). The major epistatic factor distinguishing the milder presentation in tribals vs. a more severe manifestation in nontribals was the very high frequency (0.97) of the α‐thalassemia gene in the former as compared to the latter (0.24). We conclude that the phenotypic expression of sickle‐cell anemia, linked to the Arab‐India haplotype and expressing similar levels of HbF and F cells, is not uniformly mild in India and that α‐thalassemia is a powerful and additional epistatic factor in the Indian subcontinent. Am. J. Hematol. 55:104‐109, 1997.

HIV-1 DNA shedding in genital ulcers and its associated risk factors in Pune, India

HIV infection status was determined in 302 consecutive patients with genital ulcer disease (GUD) presenting to two sexually transmitted disease (STD) clinics in Pune, India. Of the 71 (24%) individuals with HIV infection, 67 (94%) were HIV antibody-positive, and 4 (6%) were HIV antibody-negative but p24 antigen-positive at the time of presentation. HIV-1 DNA was detected in 24 (34%) specimens. The genital ulcers of all four acutely infected p24-antigenemic subjects were HIV-1 DNA-positive by polymerase chain reaction (PCR) assay, compared with 20 of 67 (30%) seropositive patients (p = .01). Presence of chancroid, GUD symptoms for > 10 days, and concurrent diagnosis of cervicitis or urethritis were significantly associated risk factors for HIV-1 DNA shedding in ulcers. Early GUD diagnosis and aggressive treatment of HIV-infected patients may significantly reduce secondary transmission of HIV to other sex partners.

Prevalence and incidence of hepatitis B virus infection in STD clinic attendees in Pune, India

Objectives: To estimate the prevalence and incidence of hepatitis B virus (HBV) infection among patients attending three STD clinics in Pune, India, and to identify associated risk factors. Methods: Of the 2098 patients screened at STD clinics in Pune during 1996, 497, who returned for at least one follow up visit, were screened for various markers of HBV infection (HBsAg, anti-HBs, anti-HBc), HIV antibody, and VDRL. Results: Of the 497 participants 3.6%, 26.5%, and 43.2% were positive for HBsAg, anti-HBs, and anti-HBc respectively. Tattooing (AOR 1.64, 95% CI 1.03 to 2.64) was found to be independently associated with presence of core antibody. Additionally, history of being in commercial sex work and history of a genital ulcer were independently associated with a positive anti-HBc antibody test (AOR 12.45, 95% CI 5.58 to 27.82 and AOR 1.70, 95% CI 1.09 to 2.66, respectively). 72 out of 497 (14.5%) participants were HIV positive at baseline. HIV-1 antibody positive patients were more likely to have a positive anti-HBc test (69.4% v 39.0%, p<0.001). 30 out of 282 participants, negative for anti-HBc antibody at enrolment, seroconverted subsequently, resulting in an incidence of 10.86 per 100 person years (95% CI 7.2%, 14.5%) (mean and accumulated follow up of 11.7 months and 276.17 person years, respectively). Conclusions: A high prevalence and incidence of HBV infection, seen in STD clinic attendees underscore the need to provide HBV vaccine to commercial sex workers and their clients in India.

High-risk behaviour in young men attending sexually transmitted disease clinics in Pune, India.

The present study reports sexual risk factors associated with HIV infection among men attending two sexually transmitted disease (STD) clinics in Pune, India and compares these behaviours between young and older men. Between April 1998 and May 2000, 1,872 STD patients were screened for HIV infection. Data on demographics, medical history and sexual behaviour were collected at baseline. The overall HIV prevalence was 22.2%. HIV risk was associated with being divorced or widowed, less educated, living away from the family, having multiple sexual partners and initiation of sex at an early age. The risk behaviours in younger men were different to older men. Younger men were more likely to report early age of initiation of sex, having friends, acquaintances or commercial sex workers as their regular partners, having premarital sex and bisexual orientation. Young men were more educated and reported condom use more frequently compared with the older men. Similar high HIV prevalence among younger and older men highlights the need for focused targeted interventions aimed at adolescents and young men and also appropriate interventions for older men to reduce the risk of HIV and STD acquisition.

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.

Low carotenoid concentration and the risk of HIV seroconversion in Pune, India.

Summary: Low vitamin A and carotenoid levels could increase the risk of sexual HIV acquisition by altering the integrity of the genital epithelium or by immunologic dysfunction. We addressed this issue by measuring serum vitamin A and carotenoid levels in patients who were at risk of subsequent HIV infection. In a nested casecontrol study in individuals attending two sexually transmitted disease (STD) clinics in Pune, India, serum micronutrient levels were measured in 44 cases with documented HIV seroconversion (11 women and 33 men) and in STD patients matched for gender and length of follow‐up with no subsequent HIV seroconversion (controls). STD patients in Pune had low vitamin A and carotenoid levels, and low serum &bgr;‐carotene levels were independently associated with an increased risk of subsequent HIV seroconversion. STD patients with &bgr;‐carotene levels less than 0.075 &mgr;mol/L were 21 times more likely to acquire HIV infection than those with higher levels (adjusted odds ratio = 21.1;/p = .01). No such association was observed in case of other non‐provitamin A carotenoids. This study reports the first evidence of an association between low serum provitamin A carotenoid levels and an increased risk for heterosexual HIV acquisition in STD patients in Pune, India.