Mentored Scientist Award

The use of highly active antiretroviral therapy (HAART) has resulted in the marked decline in the morbidity and mortality associated with HIV infection. However, despite this success, current antiretroviral therapy has limitations and does not achieve a cure. Eradication of HIV will likely require a combination of strategies, including therapies that bolster the host?s immune system and that re-activate the HIV latent reservoirs. The majority of the latent reservoir in treated patients resides in the secondary lymphoid tissues including lymph nodes.

Tuberculosis (TB) is the leading cause of death for people infected with HIV worldwide. Active TB disease is largely driven by a vast reservoir of latent TB infection (LTBI), most of which has already been established by the age of five. ^1,2 However, the epidemiology of TB acquisition prior to the age of 5 is poorly understood in high TB burden countries. Additionally, there is a significant gap in knowledge of TB acquisition dynamics in HIV-exposed, un-infected children - a growing group of children due to advances in Prevention of Mother to Child Transmission.

Untreated HIV-1 infection is characterized by a progressive depletion of CD4 T cells that clinically culminates in AIDS. Our understanding of the mechanisms underlying CD4 T-cell death remains rudimentary. By infecting lymphoid cell cultures ex vivo, we have found that the vast majority of HIV-1-infected CD4 T cells do not die as a result of productive viral infection, but rather these cells die due to abortive infection where cytosolic viral DNA triggers a suicidal antiviral innate immune response.

Recent studies in the current era of combination antiretroviral therapy demonstrate an increased risk of cerebrovascular disease (CeVD) in HIV-infected individuals compared with uninfected controls, independent of traditional stroke risk factors. As the HIV-infected population ages, the clinical and public health impact of this elevated risk is predicted to grow. Despite the increased cerebrovascular risk, no tools exist to stratify HIV-infected individuals by their risk of stroke.

South Africa's HIV/AIDS epidemic is among the largest in the world in terms of its breadth and consequences. Despite rapid expansions in antiretroviral therapy (ART), a large number of HIV-positive individuals remain disengaged in care and treatment after diagnosis. In sub-Saharan Africa, relationship dynamics play an important role on HIV-related behavior, however, it is unclear how these factors affect decision-making along the treatment cascade.

Tenofovir disoproxil fumarate (TDF) is used commonly in HIV treatment and prevention settings, but factors that correlate with TDF exposure are unknown. Recent data have identified clinical factors that are associated with renal toxicity related to TDF and elevated TDF area-under-the-curve (AUC) concentrations. An elevated AUC, as a robust measure of drug exposure, is hypothesized to contribute to TDF-related kidney disease, but this has yet to be definitively shown. Furthermore, genetic factors underlying elevations in TDF AUC have not been delineated.

HIV-infected individuals on otherwise effective therapy have a higher than expected risk of cardiovascular disease (CVD). MicroRNAs (miRNAs) have emerged as potential, promising biomarkers that can not only provide incremental value over current risk prediction models for CVD but can also shed light on the molecular mechanisms underlying HIV-associated CVD.

In contrast to prior strategies for the prevention of mother-to-child transmission (PMTCT) of HIV that employed antiretroviral monotherapy and short courses of combination prophylaxis, the 2013 World Health Organization Consolidated Guidelines now recommend combination antiretroviral therapy (cART) for all HIV-infected pregnant and breastfeeding women, regardless of CD4 cell count, and encourage lifelong cART (Option B+). B+ has the potential to improve maternal health and mortality and reduce vertical transmission and sexual transmission to partners.