The trial profile is given in . There were 7274 men who were screened and 922 HIV-infected men that were enrolled and randomized. Of the 474 HIV-infected intervention arm men at enrollment, 374 (78.9%) reported being married or in consensual union, and 291 (77.8%) had a female partner who consented to participate. Of the 448 HIV-infected control arm men at enrollment, 348 (77.6%) reported being married or in consensual union, and 239 (68.7%) had a female partner who consented to participate. The difference between arms in the proportions of female partners who consented to participation was statistically significant (p=0.007). There were 80 (27.5%) women in the intervention arm and 68 (28.5%) women in the control arm who did not have an enrollment vaginal swab collected due to a temporary stock outage of HPV Digene swabs which affected both arms simultaneously and equally. Thus, there were 211 (72.5%) concurrently enrolled female partners of HIV-infected men who provided an enrollment vaginal swab in the intervention arm, and 171 (71.5%) in the control arm. The number of women exceeded the number of enrolled men because of polygamous relationships, with 211 women in a consensual union with 193 men in the intervention arm (mean=1.09 female partners per married man) and 171 women in a consensual union with 155 men in the control arm (mean=1.10 female partners per married man).
The female retention rates at the year one follow-up visit were 88.2% (186/211) in the intervention arm and 86.5% (148/171) in the control arm. At the second year follow-up, female retention rates were 75.8% (160/211) in the intervention group and 77.2% (132/171) in the control group.
Male baseline sociodemographic characteristics, sexual behaviors, and symptoms of STIs were similar between male study arm participants, except that a greater proportion of men in the intervention arm did not use condoms (p=0.03) (). At enrollment, the male HR-HPV prevalence was 73.2% (134/183) in the intervention arm and 69.3% (104/150) in the control arm (PRR 1.06, 95%CI 0.92–1.21, p =0.43) (). The overall male HR-HPV prevalence was 71.5% (238/333) for any HR-HPV genotype and was 44.4% (148/333) for multiple HR-HPV genotypes.
Baseline characteristics, risk behaviors, and symptoms of sexually transmitted infections of men and their female partners by study arm.
The female enrollment characteristics were generally similar between study arms, except the intervention arm women were younger (p=0.04), more likely to be in a monogamous relationship (p=0.09), and reported lower condom use (p=0.07) (). HIV prevalence at enrollment was 64.0% among the female partners of intervention arm men and 62.0% among the female partners of the control arm men (). The prevalence of HR-HPV at enrollment was 67.0% in the women married to intervention arm men and 61.9% in the women married to control arm men (PRR 1.08, 95%CI 0.93–1.26, p =0.64) ().
Female HPV prevalence at enrollment, and at 12 and 24 months follow-up, by male circumcision study arm
In the primary intention-to-treat analyses, the prevalence of female HR-HPV infection at year two was 55.4% in the intervention arm and 51.9% in the control arm (PRR = 1.07, 95%CI 0.86–1.32, p=0.64) (). In an as-treated analysis, the prevalence of any HR-HPV infections at year two was 54.2% (78/144) in female partners of circumcised men and 54.3% (75/138) in female partners of uncircumcised men (PRR = 1.00, 95%CI 0.80–1.24, p= 1.00). There was also no difference in LR-HPV prevalence between the two arms (intervention 62.3%, control 61.1%, PRR=1.02, 95%CI 0.85–1.22, p=0.90) ().
Over the two-year follow-up, the incidence of HR-HPV was 32.0/100py in intervention arm female partners and 30.6/100py in control arm female partners (IRR= 1.05, 95%CI 0.77–1.43, p=0.78) (). After adjustment for female age, number of partners during the past year (single or multiple partners), and condom use (no use or some/always use), the adjusted IRR of any HR-HPV acquisition in female partners of intervention relative to control arm men was IRR=0.98 (95%CI 0.74–1.28, p=0.86). There also was no difference between the two arms in LR-HPV incidence over the two year follow-up (IRR=0.98, 95%CI 0.74–1.31, p=0.90) (). In a subgroup analysis of women who were negative for HR-HPV at enrollment, the incidence of HR-HPV over the two-year follow-up was 25.1/100py (26/103.5 py) in intervention arm female partners and 20.8/100py (20/96 py) in control arm female partners (IRR= 1.20, 95%CI 0.67–2.16, p=0.53).
Female HPV incidence by study arm and follow-up interval for participants with amplifiable cellular and/or viral DNA at sequential study visits. N is the number of women with newly detected HPV infections.
In addition, there was no difference in genotype-specific HR-HPV clearance (i.e., loss of detection) among the female partners of men in the intervention arm (46.2%, 196/424) compared to female partners of control arm men (48.1%, 167/347, RR=0.96, 95%CI 0.83–1.12, p=0.61) ().
Table 4 Clearance of pre-existing genotype-specific female HR-HPV infections by study arm. The denominators (N) are individuals with the specified genotype who had amplifiable cellular and/or viral DNA at both enrollment and follow-up, and were positive for the (more ...)
To further assess the lack of efficacy of MC to reduce HR-HPV in female partners of HIV-infected men, we conducted a sensitivity analysis based on the female HIV status. The overall prevalence of female HR-HPV at enrollment was higher among the HIV-infected women (74.5%, 178/239) compared to the HIV-uninfected women (47.8%, 66/138) (p<0.001). The prevalence of female HR-HPV among enrollment HIV-uninfected women at year two was 43.1% (25/58) in the intervention arm and 32.7% (18/55) in the control arm (PRR=1.32, 95%CI 0.81–2.13, p=0.33) (). The prevalence of female HR-HPV among enrollment HIV-infected women at year two was 62.4% (63/101) in the intervention arm and 65.8% (50/76) in the control arm (PRR=0.95, 95%CI 0.76–1.18, p=0.75) (). The effect of MC on HR-HPV incidence over the two year follow-up was similar for HIV-uninfected females (IRR=0.98, 95%CI 0.57–1.68, p=0.93) and HIV-infected females (IRR=1.07, 95%CI 0.73–1.56, p=0.74). The effect of MC on genotype-specific HR-HPV clearance among the HIV-uninfected female partners (RR=1.00, 95%CI 0.81–1.24, p=1.00) was similar to the HIV-infected female partners (RR=0.98, 95%CI 0.81–1.18, p=0.80).
Female HPV prevalence at enrollment, and at 12 and 24 months follow-up, by male circumcision study arm and stratified by female partner enrollment HIV status.