Association of human papillomavirus on risk of HIV acquisition in African women: analyses from MTN-020/ASPIRE

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BACKGROUND: Observational data on the synergy between human papillomavirus (HPV) infection and risk for HIV acquisition are needed. HPV clearance, associated with an influx of cells targeted by HIV, may increase HIV risk. This study examined the association between HPV and HIV acquisition using endocervical swabs collected in MTN-020/ASPIRE. METHODS: Healthy, sexually active women without HIV participating in the ASPIRE dapivirine ring study in Malawi, South Africa, Uganda, and Zimbabwe provided endocervical swabs monthly, which were tested for HPV-DNA. HPV status was classified into prevalent, persistent (HPV+ for at least 4 months), HPV clearance (HPV+ followed by HPV-), HPV acquisition (HPV- followed by HPV+), and remaining HPV positive (2 subsequent HPV+). Cox time-varying regression models were used to assess associations between HPV states and HIV acquisition. RESULTS: Among 91 HIV acquisition endpoints, HPV clearance increased HIV risk for high-risk types (16/18/31/33/35/45/52/58) (HR = 2.40, 95% CI = 1.59 to 3.62). Remaining HPV+ also showed a moderately increased risk (HR = 1.59, 95% CI = 1.07 to 2.35), while prevalent, persistent, and HPV acquisition events showed non-significant associations. Elevated HIV risk was also observed for clearance of HPV16/18, other high-risk types, low-risk types, and HPV6/11. There was also a dose-response relationship, with HIV risk increasing by 1.75-fold (95% CI = 1.55 to 1.96) for each additional HPV type cleared. CONCLUSIONS: HPV clearance-related immune activation is strongly linked to HIV acquisition, likely due to increased CD4+ T cells and inflammation. These findings support HPV vaccination as a potential HIV prevention strategy and highlight the need to integrate HIV prevention into cervical cancer programs.

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