UCLA

Introduction: Chronic inflammation is a major contributor to increased morbidity and mortality among people living with HIV. Research suggests that the composition of the gastrointestinal microbiome may be altered by HIV, resulting in a state of “dysbiosis” that exacerbates and perpetuates immune dysfunction. However, studies of HIV and the microbiome have thus far been limited by small sample sizes and poor control for confounding factors and have not considered potentially synergistic effects of comorbidities such as obesity and methamphetamine (MA) use. Therefore, the effects of HIV on the microbiome remain unclear.

Methods: This dissertation includes biomarker, behavioral, and clinical data from 381 diverse young men who have sex with men. Microbiome composition was assessed by targeted sequencing of the V4 region of the 16S rRNA gene using rectal swab samples. In Chapter 2, we examined differences in microbiome composition between men with increasing levels of plasma HIV RNA. In Chapter 3, we split the sample into groups based on HIV and obesity and compared men who were HIV+ and obese to those with only one or neither conditions. In Chapter 4, we explored the effects of MA use on the microbiome while testing for potential interactions between MA use and HIV status. All comparisons utilized inverse probability of treatment weighting to control for confounding by numerous behavioral and clinical factors.

Results: HIV, obesity, and MA use were all associated with shifts in microbial composition consistent with a pro-inflammatory environment. There was a dose-dependent relationship between HIV RNA level and severity of dysbiosis. Men who were HIV+ and obese had more severe dysbiosis than those with only one or neither conditions. Regardless of HIV status, MA users had higher relative abundance of many pro-inflammatory bacterial genera, with frequent users having the highest amounts.

Conclusions: As multiple comorbid conditions can negatively impact the microbiome, interventions to address dysbiosis and reduce its inflammatory consequences should consider interactions between these conditions. Future studies should utilize analytic approaches such as those employed in this dissertation in order to limit the effects of confounding and improve comparability.