BackgroundFor women living with HIV (WLHIV), the burden of persistent HPV infection, cervical pre-cancerous lesions and cancer have been demonstrated to be higher than among HIV-negative women. As Ghana and other lower-middle-income countries (LMIC) work toward developing national cervical cancer programmes, it is essential that local scientific evidence be provided to guide policy decisions, especially for such special populations. The objective of this study was to determine the distribution of high-risk HPV genotype and related factors among WLHIV and its implication for the prevention of cervical cancer prevention efforts.MethodsA cross-sectional study was conducted at the Cape Coast Teaching Hospital in Ghana. WLHIV, aged 25–65 years, who met the eligibility criteria were recruited through a simple random sampling method. An interviewer-administered questionnaire was used to gather socio-demographic, behavioural, clinical and other pertinent information. The AmpFire HPV detection system (Atila BioSystem, Mointain View, CA was used to detect 15 high-risk HPV genotypes from self-collected cervico-vaginal samples. The data collected were exported to STATA 16.0 for statistical analysis.ResultsIn all, 330 study participants, with mean age of 47.2 years (SD ± 10.7), were involved. Most (69.1%, n = 188/272) had HIV viral loads < 1000 copies/ml and 41.2% (n = 136) had ever heard of cervical screening. The overall hr-HPV prevalence was 42.7% (n = 141, 95% CI 37.4–48.1) and the five commonest hr-HPV types among screen positives were HPV59 (50.4%), HPV18 (30.5%), HPV35 (26.2%), HPV58 (17%) and HPV45 (14.9%). Most infected women (60.3%, n = 85) had multiple hr-HPV infections, with about 57.4% (n = 81) having 2–5 h-HPV types, while 2.8% (n = 4) had more than five hr-HPV types. A total of 37.6% (n = 53) had HPV16 and/or18, while 66.0% (n = 93) had the hr-HPV genotypes covered by the nonavalent vaccine. Women with HIV viral load ≥ 1000copies/ml (AOR = 5.58, 95% CI 2.89–10.78,p< 0.001) had a higher likelihood of being co-infected.ConclusionThis study found out that the prevalence of hr-HPV still remains high in women with HIV, with a notable occurrence of multiple infections and infection with genotypes 16 and/or18. Additionally, an association was established between hr-HPV and infection HIV viral load.. Therefore, comprehensive HIV care for these women should include awareness of cervical cancer, consideration of vaccination and implementation of screening and follow-up protocols. National programmes in LMIC, such as Ghana, should consider using HPV-based screen-triage-treat approach with partial genotyping.