Herpes simplex virus type 2 (HSV-2) infection significantly increases the risk of HIV infection in Ugandan and Zimbabwean women, according to the findings of a prospective cohort study published in the July 31st edition of the journal AIDS. Among women who acquired HSV-2 during the study, the risk of HIV infection was eight times higher than for women without HSV-2.
The authors call for the urgent implementation of known HSV-2 control measures as well as the identification of new control measures against HSV-2 to check the spread of HIV.
However, a study presented last week at the IAS Conference on HIV Pathogenesis, Treatment and Prevention showed no protective effect of aciclovir, a drug that suppresses HSV-2, against HIV infection in a large randomised study in Tanzanian women, possibly due to low adherence rates.
Nevertheless, there is incontrovertible evidence that genital ulcers in both sexes are a risk factor for HIV transmission. HSV-2, the cause of genital herpes, a common sexually transmitted infection (STI), is the commonest cause of genital ulcers worldwide.
HSV-2 is a prevalent co-infection in regions with an escalating HIV/AIDS problem which may facilitate HIV infection. Herpetic reactivation is accompanied by an influx of CD4-bearing lymphocytes which increases the number of HIV target cells in the genital mucosa of patients with HSV-2.
Propective studies have demonstrated a significant association between HSV-2 and HIV infection in men. However, the studies in women have yielded mixed results; some studies showed an increased risk while others did not.
The sex difference for HSV-2 as a risk factor for HIV infection might be attributable to differences in HIV transmission dynamics between men and women, and the fact that previous studies had small sample sizes and an incomplete control of confounding.
Thus, despite the strong biological plausibility that HSV-2 might be a risk factor for HIV, there is a lack of consistent supportive epidemiological data for women. A team of US, Ugandan, and Zimbabwean investigators re-examined this issue by measuring the effect of prevalent and incident HSV-2 infections on the acquisition of HIV infection.
The study took place at three sites in Kampala, Uganda and four sites in Harare and Chitungwiza, Zimbabwe. The study was nested within a large cohort study evaluating the effect of hormonal contraceptive use on HIV acquisition. The study population were women seeking reproductive and general health care services between November 1999 and January 2004.
Study participants were sexually active, aged 18-35 years, HIV negative at screening, not pregnant, using combined oral contraceptives every 12 weeks, or not using hormonal contraceptives for at least 3 months.
At enrollment, the women completed a standardized interview to assess sociodemographic characteristics as well as reproductive, sexual, and STI histories and current sexual partners. The study participants received contraceptive counselling, HIV/STI risk reduction counseling, condom use counselling, condoms, and hormonal contraception. Treatment was provided for STIs.
Laboratory investigations included enzyme-linked immunoabsorbent assays (ELISAs) for HSV-2 and HIV, Western blotting to confirm the results of HIV ELISA, and HIV DNA PCR. HIV positive women received post-test counselling and were referred for medical care and pyscho-social support.
Women who were HIV negative at baseline were followed up every 12 weeks for 15-24 months. Follow up procedures were similar to those at enrollment. A total of 4531 sexually active, HIV-uninfected women (2235 in Uganda and 2296 in Zimbabwe) with a median age of 25 years were followed up. The association between prior HSV-2 infection and HIV acquisition was estimated using a statistical model.
HSV-2 seroprevalence at enrollment was 52 % in Uganda and 53 % in Zimbabwe. HSV-2 seroincidence during follow-up was 9.6 and 8.8/100 person-years in Uganda and Zimbabwe, respectively. In Uganda, 530 women (24 %) reported having at least one genital ulcer during follow up. Of these 530 women, prevalent and incident HSV-2 were 57 and 3 %, respectively. In Zimbabwe, 188 women (12 %) reported having at least one genital ulcer during follow up and prevalent and incident HSV-2 was 81 and 5 %, respectively.
In Uganda, the hazard ratio (HR) for HIV was 2.8 [95% confidence interval (CI), 1.5–5.3] among women with seroprevalent HSV-2 and 4.6 (95% CI, 1.6–13.1) among women with seroincident HSV-2, adjusted for confounding. In Zimbabwe, the HR for HIV was 4.4 (95% CI, 2.7–7.2) among women with seroprevalent HSV-2, and 8.6 (95% CI, 4.3–17.1) among women with seroincident HSV-2, also adjusted for confounding. In both countries, HIV incidence was higher among women with HSV-2 infection compared with women without HSV-2.
The population attributable risk percent for HIV infection due to prevalent and incident HSV-2 infection was 42% in Uganda and 65% in Zimbabwe. Overall, approximately 84 % of all HIV seroconversions (178/211) were in women with prior HSV-2 infection.
The findings of Brown et al provide new and strong evidence that HSV-2 plays an important role in HIV transmission in women. The policy implication is that the control of HSV-2 remains an urgent public health imperative for the prevention of HIV.
Brown JM et al. Incident and prevalent herpes simplex virus type 2 infection increases risk of HIV acquisition among women in Uganda and Zimbabwe. AIDS 21:1515-1523, 2007.