Each year, there are more than 1 million pregnant women living with HIV (PWLHIV) who receive antiretroviral medications (ARVs) for treatment and perinatal and postnatal HIV transmission prevention, with new ARVs introduced at a rapid pace. Although maternal use of ARVs has successfully reduced perinatal HIV transmission, there remains a clear need to monitor the safety of in utero ARV for infant and child health. PHACS 2020 is designed as a Program Project P01 grant, consisting of four support Cores and 2-4 research projects. This multidisciplinary, interdisciplinary, transdisciplinary and synergistic P01 will address the most critical scientific questions for children, youth and young adults exposed to or living with HIV. This supplement specifically addresses the research agenda proposed in the prime award: PHACS2020 Adolescent Master Protocol Up Series (AmpUP). Over 300,000 women die each year from squamous cell cancers of the cervix caused by persistent infection with high-risk (i.e. oncogenic) human papillomavirus (hrHPV). The HPV vaccine has been a transforming event, capable of preventing cervical cancer globally. Although HIV infection is an established risk factor for HPV-associated cancers in adults, the natural history of HPV among young women living with perinatal HIV (YWLPHIV) is not well established. In a recent PHACS study of HPV-vaccinated youth, YWLPHIV had lower HPV antibody titers than perinatally HIV exposed but uninfected young women (YWLPHEU) and high rates of abnormal cytology. It is essential to understand factors associated with persistence of hrHPV vaccine and non-vaccine HPV types in HPV vaccinated YWLHIV. Vaginal microbiome dysbiosis has been associated with hrHPV persistence, possibly through dysbiosis-induced inflammation and consequent epithelial disruption with release of known carcinogenic products. In this study, we propose to take advantage of PHACS unique infrastructure and biorepository. From assays on annual vaginal samples collected by women in PHACS III, we will identify women with hrHPV persistence vs clearance and determine the role of microbial dysbiosis (16S rRNA sequencing) and inflammation (multiplex cytokine assays metabolic profiles) on hrHPV persistence in YWLPHIV and YWLPHEU who have been vaccinated against HPV. The results of this study will be critical for developing treatment strategies (such as the use of vaginal probiotics) and cervical cancer screening guidelines for WLPHIV in resourced and resource limited settings.
Since HPV persistence is linked to cervical cancer development, understanding the natural history of HPV infections in young women living with perinatal HIV (YWLPHIV) is critical. This study will take advantage of the PHACS biorepository to examine factors that influence HPV persistence in YWLPHIV including the vaginal microbiome and associated inflammatory states. Discoveries from this study could lead to treatment such as vaginal probiotics and new biomarkers to identify early disease.
