UC San Diego

Research on human immunodeficiency virus type I (HIV-1) has led to the development and use of different antiretroviral therapies (ART) to effectively inhibit viral replication and to decrease the transmission rates. However, poor adherence or interruption of therapy may select for drug resistance which leads to a decrease in the overall effectiveness of ART. Even though there is research performed to understand drug resistance mutations through blood sampling, there is a need to understand HIV drug resistance in tissues outside of blood in people living with HIV. For this study, various tissues of two participants with HIV in the Last Gift cohort were examined. HIV drug-resistance mutations and viral populations were obtained through single-genome amplification of the full-length HIV pol gene. The results obtained showed that there were many sequences found within and across various tissues that had nearly identical sequences, which might be due to viral migration. The lymph nodes and spleen exhibited high levels of DRMs to more than one class of ART. We also observed that drugs taken early after HIV diagnosis possibly selected for DRMs that were archived in HIV reservoirs. Also, PBMCs from whole blood did not have certain DRMs that were present in other tissues of the corresponding participants. Overall, the study suggests blood may not be fully capable of characterizing viral reservoirs in other anatomical locations. These findings, in hopes, can provide aid in improving current ART regimens for people living with HIV worldwide.