Sexual risk factors for HIV infection in early and advanced HIV epidemics in sub-Saharan Africa: systematic overview of 68 epidemiological studies

Abstract

Background: It is commonly assumed that sexual risk factors for heterosexual HIV transmission in sub-Saharan Africa, such as multi-partner sex, paid sex and co-infections, become less important as HIV epidemics mature and prevalence increases.

Methods and findings: We conducted a systematic review of 68 African epidemiological studies from 1986 to 2006 involving 17,000 HIV positive adults and 73,000 controls. We used random-effects methods and stratified results by gender, time, background HIV prevalence rates and other variables. The number of sex partners, history of paid sex, and infection with herpes simplex virus (HSV-2) or other sexually-transmitted infections (STIs) each showed significant associations with HIV infection. Among the general population, the odds ratio (OR) of HIV infection for women reporting 3+ sex partners versus 0-2 was 3.64 (95%CI [2.87-4.62]), with similar risks for men. About 9% of infected women reported ever having been paid for sex, versus 4% of control women (OR = 2.29, [1.45-3.62]). About 31% of infected men reported ever paying for sex versus 18% of uninfected men (OR = 1.75, [1.30-2.36]). HSV-2 infection carried the largest risk of HIV infection: OR = 4.62, [2.85-7.47] in women, and OR = 6.97, [4.68-10.38] in men. These risks changed little over time and stratification by lower and higher HIV background prevalence showed that risk ratios for most variables were larger in high prevalence settings. Among uninfected controls, the male-female differences in the number of sex partners and in paid sex were more extreme in the higher HIV prevalence settings than in the lower prevalence settings.

Significance: Multi-partner sex, paid sex, STIs and HSV-2 infection are as important to HIV transmission in advanced as in early HIV epidemics. Even in high prevalence settings, prevention among people with high rates of partner change, such as female sex workers and their male clients, is likely to reduce transmission overall.

Figure 1. Summary odds ratios of risk factors for HIV among the general population for women and men. Notes:

* n/N represents the number of HIV-positive individuals with exposure to the risk factor over the total number of HIV-positive individuals. † n/N represents the number of HIV-negative individuals with exposure to the risk factor over total number of HIV-negative individuals. The size of the square is proportional to the size of the total population

Figure 2. Studies of HIV and selected risk factors in Africa. Notes:

* n/N represents the number of HIV-positive individuals with exposure to the risk factor over the total number of HIV-positive individuals. † n/N represents the number of HIV-negative individuals with exposure to the risk factor over the total number of HIV-negative individuals. ‡ Heterogeneity is tested by chi-square (p<0.05 indicates a significant heterogeneity). I-squared reflects the variation in summary OR attributable to heterogeneity among studies. ** Weighted linear regression method is used to test the linear trend of ORs by the study year (p<0.05 indicates a significant trend). Each risk factor is listed by order of the study year. The size of the square is proportional to the weight of the respective OR. Different scales are used for HSV-2 studies

Figure 3. Studies of HIV and selected risk factors in Africa. Notes:

* n/N represents the number of HIV-positive individuals with exposure to the risk factor over the total number of HIV-positive individuals. † n/N represents the number of HIV-negative individuals with exposure to the risk factor over the total number of HIV-negative individuals. ‡ Heterogeneity is tested by chi-square (p<0.05 indicates a significant heterogeneity). I-squared reflects the variation in summary OR attributable to heterogeneity among studies. ** Weighted linear regression method is used to test the linear trend of ORs by the study year (p<0.05 indicates a significant trend). Each risk factor is listed by order of the study year. The size of the square is proportional to the weight of the respective OR. Different scales are used for HSV-2 studies

Figure 4. Sex partners (3+ vs. 0–2) by lower and higher background HIV prevalence. Notes:

* Heterogeneity is tested by chi-square (p<0.05 indicates a significant heterogeneity). The size of the square is proportional to the weight of the respective OR. Different scales are used for HSV-2 studies

Figure 5. History of STI by lower and higher background HIV prevalence. Notes:

* Heterogeneity is tested by chi-square (p<0.05 indicates a significant heterogeneity). The size of the square is proportional to the weight of the respective OR. Different scales are used for HSV-2 studies

Figure 6. HSV-2by lower and higher background HIV prevalence. Notes:

* Heterogeneity is tested by chi-square (p<0.05 indicates a significant heterogeneity). The size of the square is proportional to the weight of the respective OR. Different scales are used for HSV-2 studies

Figure 7. Male-female prevalence ratios for sexual risk factors among HIV-negative general populations, by lower and higher background HIV prevalence. Notes:

* Prevalence ratio equals the rate of exposure among HIV-negative men over that of HIV-negative women.

Figure 8. Begg's funnel plots with 95% CI for publication bias by risk factors (p<0.05 indicates a significant bias).