The incidence of HIV-1 infection among heterosexual partners of HIV-infected persons has been reported to range between 4.6 and 11.8 per 100 person-years in previous studies.1-4 Several behavioural and biologic factors such as high viral load, advanced HIV disease, sexually transmitted infections (STIs) in the HIV-infected partners, lack of consistent condom use, frequent sexual contact, and anal intercourse have been associated with an increased risk of HIV-1 transmission among heterosexual sero-discordant couples.5-8
India has a burden of estimated over 5.1 million adults and children living with HIV/AIDS9 and heterosexual transmission is responsible for more than 80% of all HIV-1 transmissions.10 The major risk factor for HIV-1 infection among married monogamous Indian women is sexual contact with their husbands practicing high-risk behaviour.11 However, the rate of HIV transmission among couples has not yet been estimated in India. This is the first report of HIV-1 incidence among sero-discordant couples from India.
Between September 2002 and November 2004, a total of 457 consenting HIV-1 sero-discordant couples were enrolled and followed quarterly in a prospective study in Pune, India. All participants were aware of their partner's HIV status at study entry. Intensive individual pre and post-HIV test counseling, couples' counseling for risk reduction including condom use counseling were provided. Condoms were also provided to the couples. Risk behavior assessments were carried out at the time of pre-test counseling at the screening visit on a 1:1 basis by trained interviewers who were often aware of the HIV sero-status of the interviewee. Sexual behavior history was collected at 3 monthly intervals and interviewers took care not to discuss or disclose data reported by individuals to their spouses. Both the partners were educated about the protective effects of the condom use. Although specific data on acceptability was not collected, condom use was assessed at every quarterly visit. Active STIs were treated and past history of STIs was assessed. For all HIV-infected persons, CD4 T lymphocyte counts and viral loads were performed at 3 and 6 month intervals, respectively. Uninfected partners were assessed for risk behavior and HIV status every 3 months.
HIV-infected persons with a mean age of 34 years (Range 20-63 years, SD 6.9 years) were primarily men (394/457; 86%). The mean age of males was 35 years (n = 394, SD 7.4 years) and that of females was 30 years (n = 63, SD 7.9 years). Seventy-five percent of the 457 HIV-infected persons reported multiple sexual partners; 46% consumed alcohol regularly and 11% had received blood transfusion in the past two years. Twenty-one percent and 10% of HIV-infected persons reported recent episodes of genital ulcers and genital discharge, respectively. Herpes zoster (26%), tuberculosis (22%), jaundice (16%), and oral thrush (9%) were the predominant past illnesses reported by the HIV infected participants. Commonly presenting clinical conditions among HIV infected were fever (20%), weight loss (17%), loss of appetite (15%), persistent cough (14%) and skin rash (7%). At enrollment, the median CD4 T lymphocyte count was 218 cells/mm3 (range 4-1131 cells/mm3), the median viral load was 94,014 RNA copies/ml (range 422-5,653,140 RNA copies/ml) and 46% of the infected persons had CD4 T lymphocyte count <200 cells/mm3. Only 12 (2.6%) HIV-infected persons received antiretroviral therapy during the study period.
Of the 457 couples enrolled, 412 (90%) returned for at least one follow-up visit resulting in 491 person years of follow-up. The median duration of follow-up was 12 months (r ange 2.6-31.0 months). Retention rates at the 3, 6, 9, 12, 15, and 18 month follow-up visits were 95%, 91%, 89%, 90%, 78%, and 67%, respectively. By April 2005, 6 uninfected partners sero-converted, giving an HIV incidence rate of 1.22 per 100 person-years (95% CI 0.45-2.66%). HIV incidence was higher among exposed male than female partners (2.90 and 0.95 per 100 person-years) and nearly 3.5 times higher among those with multiple sexual partners than those with single sexual partners. But these differences were not statistically significant (Table 1).
A review of the published literature on HIV incidence among discordant couples suggests that the incidence of HIV infection among the heterosexual partners of infected persons in India is much lower than what has been previously reported from other countries including Uganda,1,5 Tanzania2 and Zambia6 (11.8, 5-10, 8.5/100 person-years respectively). Many of the African studies were done years ago and may not reflect the present rates in such couples. Indian discordant couples were different from previously described African discordant couples,6 demonstrating higher rates of condom use [71% vs. 3%] and lower rates of previous STIs [12-23% vs. 44-50%] at baseline. Condom use is one of the common methods of contraception in India. The low HIV incidence among these Indian HIV sero-discordant couples could also be related to a lower frequency of sex among couples in which the HIV-infected persons had advanced HIV disease (35% vs. 52% among couples with index partners having CD4 counts <200/cumm and ≥200/cumm respectively) (p<0.01). Of the six sero-converters, five HIV-infected partners had CD4 cell counts <350 cells/mm3, and among them four had viral load >30,000 copies per milliliter, reflecting more advanced HIV disease.
The median follow-up period for the Indian cohort was approximately 12 months. Additional follow-up of these couples is ongoing to determine whether the lower incidence and risk reduction is sustained over longer period of time. This would also give us an opportunity to study if there is a differential loss to follow-up that would actually under-estimate our current incidence estimate.
The lower HIV transmission rate among discordant couples in our study may also reflect a positive impact of intensive risk reduction counseling, as well as effective STI diagnosis and treatment. It is important to do similar studies in other Indian settings. This might be one among other reasons why HIV epidemics in India and Africa are different.12 It has been reported that R5 receptors are important in sexual transmission of HIV and whether this biological factor has contributed to low HIV transmission among HIV discordant couples in our study is uncertain. Such factors need to be further investigated in carefully designed studies.
The partners of HIV-infected individuals in India represent an important high-risk group in India that have not received specific targeted risk reduction education. Their risk for HIV is typically limited to exposure to an infected spouse.11,13 The monogamous female partners of infected men also represent the vast majority of women at risk for transmitting HIV to infants in India. It is, therefore, important to identify targeted and specific strategies that can reduce HIV risk to partners of infected patients in India. Our data demonstrates that discordant couples receiving intensive couples counseling, in conjunction with active treatment of other sexually transmitted diseases have lower risk for HIV than has been previously reported among HIV discordant couples elsewhere. Risk reduction programs designed to identify and counsel HIV discordant couples in India should be considered as a key strategy to reduce the risk of HIV infection in adults and children.
National AIDS Research Institute, Indian Council of Medical Research (ICMR) provided the infrastructural, operational and logistical support for this study. The ICMR and the Health Ministry Screening Committee, Government of India approved the study. The funding support was provided by the Fogarty International Center, U.S. National Institutes of Health, Program of International Training Grants in Epidemiology Related to AIDS, D43 TW00010-AITRP, as well as a contract from the NIAID, NIH through Family Health International (FHI) (AI 47968) under the HIV Prevention Trials Network (HPTN) Project. The Manuscript Review Committee (MRC) of the HPTN approved the manuscript being submitted. The views expressed do not necessarily reflect the views of the ICMR, the Johns Hopkins University, FHI or the NIH.
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