This study conducted a comparative case study analysis of the HIV program in Nigeria’s South-South and North-East regions of Nigeria to determine the access and quality of HIV care and treatment services. Service delivery is an essential component of the WHO Health systems framework. Data were collected from 385 respondents using structured questionnaires and analysed using descriptive and inferential statistics. The study found that the North-East region of Nigeria had significantly lower numbers of primary healthcare facilities and inpatient beds per 10,000 population compared to the South-South region. The North-East region had an average of 0.02 inpatient beds per 1,000 population, significantly below the WHO standard, while the South-South region had an average of 0.18 inpatient beds per 1,000 population, relatively closer to the WHO standard. The general service readiness score for delivering HIV program services was at least 94% in all health facilities in both the North-East and South-South regions. The HIV service readiness index for the North-East region was higher than that of the South-South region, with some disparities in the availability of national ART guidelines, national HIV counselling and testing guidelines, staff training, and availability of HIV prevention services. HIV testing and counselling services were described as readily available and accessible in both regions, with some communities taking ownership of promoting the availability of these services. However, both regions had a relatively high service readiness score for delivering HIV program services, with some disparities in the availability of national guidelines and training of staff. These findings demonstrate extensive investment of government and donor agencies in delivering quality HIV services with areas to improve to ensure alignment with WHO system strengthening framework. Keywords: Health systems, HIV, North-East, Service delivery, South-South, WHO.