Gad Murenzi

Long-term human papillomavirus vaccination effectiveness and immunity in Rwandan women living with and without HIV: a study protocol

Introduction Prophylactic human papillomavirus (HPV) vaccines have been shown to be highly effective in protecting women against cervical infections, high-grade abnormalities and cancer caused by the targeted HPV types. However, the evidence for their effectiveness in women living with HIV (WLWH) is less clear. Methods WLWH and HIV-negative women who likely did (birth cohorts 1996 and later) and WLWH and HIV(−) negative who likely did not (birth cohorts before 1996) receive HPV vaccination (n=3028; 757 participants for each of the four groups). Between groups, we will compare cervicovaginal, anal and oral prevalent and 6–12 month persistent HPV6/11/16/18 infections as measured using a modified AmpFire HPV genotyping assay that tests for 15 high-risk or intermediate-risk HPV genotypes, HPV6 and HPV11. We will also compare the HPV immune response in HPV-vaccinated WLWH to HPV-vaccinated HIV-negative women using an anti-HPV16 and anti-HPV18 ELISA. Vaccination status will be confirmed through national vaccination records. Analysis We will calculate point prevalence and prevalence of 6–12 month persisting infections by individual HPV-type specific infections and groups of infections for each anatomic site and for each group of women. Results will be stratified by age at vaccination, age at enrolment and the number of doses (3 vs 2) as well as other factors possibly associated with HPV prevalence. Differences in endpoints between groups, overall and between subgroups, will be tested for statistical significance (p<0.05) using Fisher’s exact or Pearson χ2 test. Differences in geometric mean titres and seropositivity will be tested for statistical significance using the Mann-Whitney and Fisher’s exact tests, respectively. Ethics and dissemination The study was approved by the Albert Einstein College of Medicine Institutional Review Board and the Rwanda National Ethics Committee. Results will be disseminated through publication in peer-reviewed journals.

Determinants of cervical high-risk human papillomavirus positivity among Rwandan women living with human immunodeficiency virus

Introduction There are few data on the prevalence of cervical high-risk human papillomavirus (hrHPV), the necessary cause of cervical cancer, and its determinants among Rwandan women living with human immunodeficiency virus (HIV). We therefore aimed to assess the determinants of hrHPV positivity among Rwandan women living with HIV (WLWH). Methods We conducted a cervical cancer screening study of ~5,000 WLWH aged 30–54 years and living in Kigali, Rwanda, but originally from all provinces in the country, from 2016–2018. Women were tested for hrHPV by the Xpert assay (Cepheid, Sunnyvale, CA, USA). A nurse-administered questionnaire collected data on demographics and HPV/cervical cancer risk factors. Women without evidence of cervical precancer and cancer were included in the analysis. Results Women included in this analysis (N = 4,880) had a mean age of 40 years, > 98% were on antiretroviral therapy, and 61% had a CD4 count of ≥500 cells/µL. High-risk HPV prevalence was 25.5% [95% confidence interval (CI)=24.3%−26.8%] and the prevalence decreased with older ages and higher CD4 counts (ptrend<0.001 for both). High-risk HPV prevalence was higher for those who reported their first sex before 16 years, had their first child before 18 years, had more sexual partners over their lifetime and in the last six months, and those with lower CD4 cell count (ptrend<0.001 for all). A CD4 count of <200 (vs. > 500) per µL was most strongly associated with being hrHPV positive (adjusted odds ratio = 2.7, 95%CI = 2.1–3.6). Conclusions Our findings highlight the role of CD4 counts, as a measure of HIV control and immunity, in controlling hrHPV infection, which could potentially impact cervical cancer control among this high-risk population. Raising awareness on various associated factors coupled with integrating HPV and cervical cancer awareness in HIV care could help control this double burden of disease.

Cervical cancer prevention and care in HIV clinics across sub‐Saharan Africa: results of a facility‐based survey

AbstractINTRODUCTIONTo eliminate cervical cancer (CC), access to and quality of prevention and care services must be monitored, particularly for women living with HIV (WLHIV). We assessed implementation practices in HIV clinics across sub‐Saharan Africa (SSA) to identify gaps in the care cascade and used aggregated patient data to populate cascades for WLHIV attending HIV clinics.METHODSOur facility‐based survey was administered between November 2020 and July 2021 in 30 HIV clinics across SSA that participate in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We performed a qualitative site‐level assessment of CC prevention and care services and analysed data from routine care of WLHIV in SSA.RESULTSHuman papillomavirus (HPV) vaccination was offered in 33% of sites. Referral for CC diagnosis (42%) and treatment (70%) was common, but not free at about 50% of sites. Most sites had electronic health information systems (90%), but data to inform indicators to monitor global targets for CC elimination in WLHIV were not routinely collected in these sites. Data were collected routinely in only 36% of sites that offered HPV vaccination, 33% of sites that offered cervical screening and 20% of sites that offered pre‐cancer and CC treatment.CONCLUSIONSThough CC prevention and care services have long been available in some HIV clinics across SSA, patient and programme monitoring need to be improved. Countries should consider leveraging their existing health information systems and use monitoring tools provided by the World Health Organization to improve CC prevention programmes and access, and to track their progress towards the goal of eliminating CC.

HPV Vaccine Effectiveness Study in Rwandan Women Living With HIV

Our study will assess and measure population effectiveness of prophylactic HPV vaccine in reducing cervical, anal, and/or oral prevalent and 6-month persistent infections among HPV-vaccinated and 757 HPV-unvaccinated Rwandan WLWH aged 18-26 years. Additional objectives include the quantification \& examination of long-term antibody (into young adulthood) responses to HPV vaccination and to validate the performance (e.g., sensitivity and specificity) of a low-cost, POC (point-of-care) anti-HPV16 antibody test to determine/confirm HPV vaccination status. The findings for this study will provide necessary evidence regarding the long-term protection afforded by HPV vaccination in WLWH living in SSA, who are at the greatest risk of HPV-related cancers.