Strong link found between herpes simplex virus-2 and HIV in sub-Saharan Africa

More evidence was presented this week by researchers from London regarding the strong link between infection with herpes simplex virus-2 (HSV-2) and the transmission of HIV, this time from an epidemiological perspective. The results of a cross-sectional study of 1000 married heterosexual couples in four cities in sub-Saharan Africa, published in the latest issue of the journal AIDS, suggest that HSV-2 is the key risk factor in promoting HIV transmission.

Data from the Multicentre Study on Factors Determining Differences in HIV Spread between African Cities analysed a cross-section, population-based study that took place between 1997 and 1998 in four sub-Saharan African cities. Kisumu, Kenya and Ndola, Zambia were chosen due to their high HIV prevalence rates, and Cotonou, Benin and Yaoundé, Cameroon, were included as they had lower overall HIV prevalence. In each city, a random sample of 1000 men and 1000 women aged 15-49 were selected from the general population through household interviews, and interview information was available for 294 couples in Kisumu, 293 in Ndola, 288 in Cotonou and 205 in Yaoundé.

For the purposes of examining the risk factors of HIV transmission within marriage, only HIV serodiscordant couples or couples where both were HIV-positive were included in the analysis. Since only those who agreed to give blood were tested for HIV, HSV-2 and syphilis, not all couples in the study had test results available, ranging from 68.4% in Kisumu to 85.4% in Yaoundé. However, based on the information available, it was found that overall, 51.1% of couples with at least one HIV-positive partner had both members who were HIV-positive. Ndola had the highest proportion of couples who were both HIV-positive (59.2%) and Yaoundé the lowest (35.7%).

Since only Kisumu and Ndola had a large enough sample of couples where at least one partner was HIV-positive, detailed analysis of risk factors was restricted to these two cities, although all four cities together were included in the larger analysis. Univariate analysis found that in each of the two cities, and overall, the strongest direct risk factor for both partners being HIV-positive was if one of both of the partners were also HSV-2-infected (odds ratio [OR] 2.7 [95% confidence interval (CI) 0.52-13.8] for one partner having HSV-2; OR 6.3 [95% CI 1.3-31.1] for both partners having HSV-2; p < 0.001 for both). The only other factors that were significant were both protective: circumcision (OR 0.48) and duration of marriage 6-10 years (OR 0.53).

Several indirect risk factors, which might be considered potential confounders, were also found to be independently associated with both couples being HIV-positive in univariate analysis. However, although the husband having had extramarital sex in the past year in Ndola was strongly significant (OR 5.1), it tended to be protective in Kisumu, and when all four cities were combined, was no longer significant. Higher education levels, on the other hand, appeared to have a protective effect, which was significant in Ndola, not quite significant in Kisumu, but approached statistical significance in all four cities combined (p = 0.06).

However, in multivariate analysis, adjusting for age and city of residence, HSV-2 status was the only factor found to be statistically significant. For the four cities combined, HSV-2 in one partner increased the risk of other partner being HIV-positive more than threefold (OR 3.4 [95% CI 0.62-18.4]) compared to couples where neither spouse was infected with HSV-2. If HSV-2 infection was found in both partners, the risk increased almost ninefold (OR 8.6 [95% CI 1.6-45.0]). Additionally, condom use was found to be protective only in Ndola (OR 0.30 [95% CI 0.09-1.0]). Further analyses looking at short-duration marriages, and analysing the two genders separately found that HSV-2 was consistently the only risk factor identified for both couples to be HIV-positive.

Although there are limitations to this study, including not knowing how or when HIV was acquired (inside or outside of the marriage, or before or during the marriage) and whether HSV-2 predated HIV or vice versa, this study’s findings agree with previous studies, including a 1998 US case-control study that identified HSV-2 as a risk factor for HIV concordance in couples.

Studies on the impact of HSV-2 therapy on HIV transmission in couples are currently underway, but the authors strongly suggest that “research on HSV-2 interventions, including vaccines, [become] a public health priority. Since many couples are discordant for HIV it is also important to identify and counsel these couples to prevent further transmission.”

An HSV-2 vaccine developed by Glaxo SmithKline showed a protective effect in women but not in men, and the company is now conducting a second large study among women in the US to confirm this finding. If the vaccine proves effective in its second phase III study, there will be considerable interest in its effects on HIV transmission in resource-limited settings. South Africa's Medical Research Council recently described a vaccine against HSV-2 as an urgent HIV prevention priority.