Intravaginal practices, bacterial vaginosis, and HIV infection in women: individual participant data meta-analysis

Abstract

Background: Identifying modifiable factors that increase women's vulnerability to HIV is a critical step in developing effective female-initiated prevention interventions. The primary objective of this study was to pool individual participant data from prospective longitudinal studies to investigate the association between intravaginal practices and acquisition of HIV infection among women in sub-Saharan Africa. Secondary objectives were to investigate associations between intravaginal practices and disrupted vaginal flora; and between disrupted vaginal flora and HIV acquisition.

Methods and findings: We conducted a meta-analysis of individual participant data from 13 prospective cohort studies involving 14,874 women, of whom 791 acquired HIV infection during 21,218 woman years of follow-up. Data were pooled using random-effects meta-analysis. The level of between-study heterogeneity was low in all analyses (I(2) values 0.0%-16.1%). Intravaginal use of cloth or paper (pooled adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.18-1.83), insertion of products to dry or tighten the vagina (aHR 1.31, 95% CI 1.00-1.71), and intravaginal cleaning with soap (aHR 1.24, 95% CI 1.01-1.53) remained associated with HIV acquisition after controlling for age, marital status, and number of sex partners in the past 3 months. Intravaginal cleaning with soap was also associated with the development of intermediate vaginal flora and bacterial vaginosis in women with normal vaginal flora at baseline (pooled adjusted odds ratio [OR] 1.24, 95% CI 1.04-1.47). Use of cloth or paper was not associated with the development of disrupted vaginal flora. Intermediate vaginal flora and bacterial vaginosis were each associated with HIV acquisition in multivariable models when measured at baseline (aHR 1.54 and 1.69, p<0.001) or at the visit before the estimated date of HIV infection (aHR 1.41 and 1.53, p<0.001), respectively.

Conclusions: This study provides evidence to suggest that some intravaginal practices increase the risk of HIV acquisition but a direct causal pathway linking intravaginal cleaning with soap, disruption of vaginal flora, and HIV acquisition has not yet been demonstrated. More consistency in the definition and measurement of specific intravaginal practices is warranted so that the effects of specific intravaginal practices and products can be further elucidated. Please see later in the article for the Editors' Summary.

Figure 1. Flow diagram of included studies.

Figure 2. Association between use of cloth or paper to wipe out vagina or apply products and HIV acquisition, ordered by country, north to south (n = 10,332).

Individual study results from Cox regression. Pooled unadjusted and aHRs from random effects meta-analysis. Reference group is women who reported no intravaginal practice or cleaning with water only. Multivariable models adjusted for age, marital status, and number of partners in last 3 mo. No estimate possible if there were no events in one group.

Figure 3. Association between intravaginal cleaning with soap and HIV acquisition, ordered by country, north to south (n = 3,071).

Individual study results from Cox regression. Pooled unadjusted and aHRs from random effects meta-analysis. Reference group is women who reported no intravaginal practice or cleaning with water only. Multivariable models adjusted for age, marital status, and number of partners in last 3 mo.

Figure 4. Association between insertion of products to dry or tighten the vagina and HIV acquisition, ordered by country, north to south(n = 9,420).

Individual study results from Cox regression. Pooled unadjusted and aHRs from random effects meta-analysis. Reference group is women who reported no intravaginal practice or cleaning with water only. Multivariable models adjusted for age, marital status, and number of partners in last 3 mo. No estimate possible if there were no events in one group. Stratum excluded if there were no events in either group, or standard error could not be estimated by model.

Figure 5. Association between intravaginal cleaning with household cleaners and HIV acquisition, ordered by country, north to south (n = 8,879).

Individual study results from Cox regression. Pooled unadjusted and aHRs from random effects meta-analysis. Reference group is women who reported no intravaginal practice or cleaning with water only. Multivariable models adjusted for age, marital status, and number of partners in last 3 mo. No estimate possible if there were no events in one group.