| Project Detail |
HIV (Human immunodeficiency virus) is a global epidemic that led to the death of over 40.1 million persons since its first report. Currently, about 38.4 million people are living with HIV (PLHV) globally; 1.9 million in Nigeria. The introduction of combination antiretroviral therapy (cART) has improved the lifespan of PLHV making it a chronic disease, yet in 2021 about 650,000 persons died from HIV-related illnesses. Efforts are being made to scale up treatment access to cART to reduce mortality. However, in recent years, a not well-understood decline in fertility of PLHV undergoing cART is a great concern for HIV treatment. Recent studies detected epigenetic abnormalities in the blood of PLHV undergoing cART with global changes in DNA methylation, where it is unclear if cART or HIV itself could be the cause. Abnormal establishment of DNA methylation in the gametes can lead to the manifestation of epimutations in the growing embryo with potentially bad consequences like embryo loss, diseases, and cancerogenesis. This study aims to determine the impact of cART on fertility and on the DNA methylome in gametes and derived embryos in the mouse as a model system. It will involve the analysis of DNA methylation changes in spermatozoa and oocytes, derived embryos, and offspring, as well as the examination of embryonic genome activation in 2-cell embryos and successful blastocyst development in early embryogenesis of mice under cART. This study will contribute to health education about HIV and its treatment, boosting the reproductive health of PLHV and, importantly, improving their compliance with antiretroviral therapy - thereby aiding the achievement of the UNAIDS target of 2030. Furthermore, It will foster the mutual transfer of expertise in andrology and HIV-biology to the host institution and will equip the applicant with novel skills in epigenetics and assisted reproduction, relevant soft skills, and new collaborations for his career development. |
