Diaphragm used with replens gel and risk of bacterial vaginosis: results from a randomized controlled trial.

BACKGROUND: Bacterial vaginosis (BV) has been linked to female HIV acquisition and transmission. We investigated the effect of providing a latex diaphragm with Replens and condoms compared to condom only on BV prevalence among participants enrolled in an HIV prevention trial. METHODS: We enrolled HIV-seronegative women and obtained a vaginal swab for diagnosis of BV using Nugent's criteria; women with BV (score 7-10) were compared to those with intermediate (score 4-6) and normal flora (score 0-3). During quarterly follow-up visits over 12-24 months a vaginal Gram stain was obtained. The primary outcome was serial point prevalence of BV during followup. RESULTS: 528 participants were enrolled; 213 (40%) had BV at enrollment. Overall, BV prevalence declined after enrollment in women with BV at baseline (OR = 0.4, 95% CI 0.29-.56) but did not differ by intervention group. In the intention-to-treat analysis BV prevalence did not differ between the intervention and control groups for women who had BV (OR = 1.01, 95% CI 0.52-1.94) or for those who did not have BV (OR = 1.21, 95% CI 0.65-2.27) at enrollment. Only 2.1% of participants were treated for symptomatic BV and few women (5-16%) were reported using anything else but water to cleanse the vagina over the course of the trial. CONCLUSIONS: Provision of the diaphragm, Replens, and condoms did not change the risk of BV in comparison to the provision of condoms alone.

Investigating Potential Associations between Cervical Procedures and HIV Acquisition.

Objective. Cervical human papillomavirus (HPV) infection has been associated with human immunodeficiency virus (HIV) acquisition in populations with a high prevalence of both infections. Procedures performed in the management of cervical dysplasia may facilitate HIV entry via mechanical injury. We sought to investigate the association between cervical procedures and incident HIV. Methods. Data on cervical cancer screening and procedures were collected in a cohort study evaluating the diaphragm for HIV prevention in 2040 women. In this secondary analysis, we investigated the association between cervical procedures and HIV acquisition. Results. Out of 2027 HIV-negative women at baseline, 199 underwent cervical procedures. Cumulative risk of HIV was 4.3% over 21 months of median followup (n = 88). Compared with women without cervical procedures, we observed no difference in HIV incidence after a cervical biopsy (RR 0.92, 95% CI 0.39-2.16), endocervical curettage (RR 0.29, 95% CI 0.07-1.22), or loop electrosurgical excision procedure (RR 1.00, 95% CI 0.30-3.30). Conclusions. In this cohort, cervical procedures were not associated with HIV incidence. This lack of association could be due to the small number of events.

Type-specific cervico-vaginal human papillomavirus infection increases risk of HIV acquisition independent of other sexually transmitted infections.

BACKGROUND: Sexually transmitted infections (STIs) such as herpes simplex virus (HSV)-2 are associated with an increased risk of HIV infection. Human papillomavirus (HPV) is a common STI, but little is know about its role in HIV transmission. The objective of this study was to determine whether cervico-vaginal HPV infection increases the risk of HIV acquisition in women independent of other common STIs. METHODS AND FINDINGS: This prospective cohort study followed 2040 HIV-negative Zimbabwean women (average age 27 years, range 18-49 years) for a median of 21 months. Participants were tested quarterly for 29 HPV types (with L1 PCR primers) and HIV (antibody testing on blood samples with DNA or RNA PCR confirmation). HIV incidence was 2.7 per 100 woman-years. Baseline HPV prevalence was 24.5%, and the most prevalent HPV types were 58 (5.0%), 16 (4.7%), 70 (2.4%), and 18 (2.3%). In separate regression models adjusting for baseline variables (including age, high risk partner, positive test for STIs, positive HSV-2 serology and condom use), HIV acquisition was associated with having baseline prevalent infection with HPV 58 (aHR 2.13; 95% CI 1.09-4.15) or HPV 70 (aHR 2.68; 95% CI 1.08-6.66). In separate regression models adjusting for both baseline variables and time-dependent variables (including HSV-2 status, incident STIs, new sexual partner and condom use), HIV acquisition was associated with concurrent infection with any non-oncogenic HPV type (aHR 1.70; 95% CI 1.02-2.85), any oncogenic HPV type (aHR 1.96; 95% CI 1.16-3.30), HPV 31 (aHR 4.25; 95% CI 1.81-9.97) or HPV 70 (aHR 3.30; 95% CI 1.50-7.20). Detection of any oncogenic HPV type within the previous 6 months was an independent predictor of HIV acquisition, regardless of whether HPV status at the HIV acquisition visit was included (aHR 1.95; 95% CI 1.19-3.21) or excluded (aHR 1.96; 95% CI 1.02-2.85) from the analysis. CONCLUSIONS/SIGNIFICANCE: Cervico-vaginal HPV infection was associated with an increased risk of HIV acquisition in women, and specific HPV types were implicated in this association. The observational nature of our study precludes establishment of causation between HPV infection and HIV acquisition. However, given the high prevalence of HPV infection in women, further investigation of the role of HPV in HIV transmission is warranted.

Cervical human papillomavirus incidence and persistence in a cohort of HIV-negative women in Zimbabwe.

BACKGROUND: Persistent infections with oncogenic human papillomavirus (HPV) types are causally related to cervical cancer. Little is known about the distribution of HPV types, independent risk factors of incidence and persistence, and patterns of persistence in sub-Saharan Africa. METHODS: A cohort of 2040 Zimbabwean women was enrolled in a randomized trial assessing the effect of diaphragm/gel provision on human immunodeficiency virus and HPV acquisition. Data from the study arms were pooled for this analysis because diaphragm/gel provision did not affect HPV acquisition and clearance. Clinicians collected cervical samples for HPV testing at enrollment, 12 months, and exit (median 21 months). RESULTS: HPV prevalence was 24.5% for any HPV type and 16.1% for oncogenic types. HPV incidence at 12 months was 23.3% for any HPV type and 11.4% for oncogenic types. HPV58 had the highest baseline prevalence (5.0%) and incidence (2.4%). Type-specific persistence was 29.8% among all HPV infections over a median of 21 months of follow-up. Baseline predictors of incident HPV infection were younger age, having more than 1 lifetime sexual partner, infrequent condom use, herpes simplex virus-2 positive serology, and having a sexually transmissible infection or a different HPV type at enrollment. Baseline predictors of persistent HPV infection were younger age, having more than 1 lifetime sexual partner, and having a high-risk partner. CONCLUSIONS: The novel association between herpes simplex virus-2 seropositivity and incident HPV infection warrants further investigation. Having a high-risk partner is a potentially modifiable risk factor for persistent HPV infection. The relatively high prevalence of HPV58 has implications for vaccine development.

Effect of diaphragm and lubricant gel provision on human papillomavirus infection among women provided with condoms: a randomized controlled trial.

OBJECTIVE: To estimate the effect of providing women with a latex diaphragm, lubricant gel, and male condoms (intervention) compared with condoms alone (control) on human papillomavirus (HPV) incidence and clearance. METHODS: Participants were 2,040 human immunodeficiency virus (HIV)-negative Zimbabwean women enrolled in a randomized trial estimating the effect of the intervention on HIV acquisition. Clinicians collected cervical samples for HPV testing at baseline, 12 months, and exit. L1 consensus polymerase chain reaction primers were used to determine HPV presence and type. RESULTS: We found no differences in the following outcomes: HPV prevalence at the time of the first postenrollment HPV test (intention-to-treat analysis, relative risk [RR] 1.02, 95% confidence interval [CI] 0.90-1.16); HPV incidence at 12 months among women HPV-negative at baseline (RR 0.95, 95% CI 0.80-1.14); and HPV clearance at 12 months among women HPV-positive at baseline (RR 0.80, 95% CI 0.61-1.05). Clearance of HPV type 58 was lower in the intervention group at 12 months (RR 0.67, 95% CI 0.48-0.92), but not at exit (RR 0.93, 95% CI 0.75-1.16); clearance of HPV type 18 was lower in the intervention group at exit (RR 0.55, 95% CI 0.33-0.89), but not at 12 months (RR 0.55, 95% CI 0.29-1.05). Women reporting diaphragm/gel use at 100% of prior sex acts had a lower likelihood of having one or more new HPV types detected at 12 months (RR 0.75, 95% CI 0.58-0.96) and exit (RR 0.77, 95% CI 0.59-0.99). CONCLUSION: Among women receiving risk reduction counseling and condoms in an HIV prevention program, diaphragm plus lubricant gel provision did not affect HPV incidence or clearance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00121459 LEVEL OF EVIDENCE: I.

Effect of Replens gel used with a diaphragm on tests for human papillomavirus and other lower genital tract infections.

OBJECTIVE: Little is known about effects of vaginal lubricants with barrier contraceptives on detection of sexually transmissible infections. We hypothesized that Replens gel used with a diaphragm would neither inhibit human papillomavirus (HPV) detection in cervical samples and chlamydia (CT) and gonorrhea (GC) detection in urine samples, nor affect cervical cytology quality. MATERIALS AND METHODS: After a clinician-collected cervical sample and a self-collected vaginal sample for HPV detection ("pregel" specimens), women placed a diaphragm containing Replens gel into the vagina. Participants (n = 77) removed the diaphragm after 6 hours and performed vaginal HPV self-sampling at several time points thereafter. Clinicians performed cervical cytology sampling and HPV testing ("postgel" specimens) 24 hours after diaphragm removal. Pregel and postgel specimens were analyzed with and without added SiHa cells (source of defined numbers of HPV16 genomes). HPV was detected by polymerase chain reaction using MY09/11 primers. Urine samples were obtained for CT and GC testing. Proportions of samples testing positive were compared using relative risk (RR) regression models. RESULTS: Proportions with detectable HPV in the clinician-collected cervical pregel and postgel samples were not statistically different for samples with added SiHa cells (88.3% vs 93.2%, RR = 1.06, 95% confidence interval = 0.96-1.14) or for native HPV infection (32.9% vs 28.2%, RR = 0.87, 95% confidence interval = 0.71-1.06). In self-collected vaginal postgel samples, there was no trend for decreased HPV detection after gel exposure. Gel affected neither urine tests for CT and GC nor cytological quality. CONCLUSIONS: Recent Replens gel use with a diaphragm does not inhibit cervical HPV testing, urine testing for CT and GC, or cervical cytology quality.