The question of whether the human brain is an anatomical site of persistent HIV-1 infection during suppressive antiretroviral therapy (ART) is critical, but remains unanswered. The presence of virus in the brains of HIV patients whose viral load is effectively suppressed would demonstrate not only the potential for CNS to act as an anatomical HIV reservoir, but also the urgent need to understand the factors contributing to persistent HIV behind the blood-brain barrier. Here, we investigated for the first time the presence of cells harboring HIV DNA and RNA in the brains from subjects with undetectable plasma viral load and sustained viral suppression, as identified by the National NeuroAIDS Tissue Consortium. Using new, highly sensitive in situ hybridization techniques, RNAscope and DNAscope, in combination with immunohistochemistry, we were able to detect HIV-1 in the brains of all virally suppressed cases and found that brain macrophages and microglia, but not astrocytes, were the cells harboring HIV DNA in the brain. This study demonstrated that HIV reservoirs persist in brain macrophages/microglia during suppressive ART, which cure/treatment strategies will need to focus on targeting.

Structural barriers to HIV care are particularly challenging in the US South, which has higher HIV diagnosis rates, poverty, uninsurance, HIV stigma, and rurality, and fewer comprehensive public health programs versus other US regions. Focusing on one structural barrier, we examined geographic accessibility to comprehensive, coordinated HIV care (HIVCCC) in the US South. We integrated publicly available data to study travel time to HIVCCC in 16 Southern states and District of Columbia. We geocoded HIVCCC service locations and estimated drive time between the population-weighted county centroid and closest HIVCCC facility. We evaluated drive time in aggregate, and by county-level HIV prevalence quintile, urbanicity, and race/ethnicity. Optimal drive time was ≤30 min, a common primary care accessibility threshold. We identified 228 service locations providing HIVCCC across 1422 Southern counties, with median drive time to care of 70 min (IQR 64 min). For 368 counties in the top HIV prevalence quintile, median drive time is 50 min (IQR 61 min), exceeding 60 min in over one-third of these counties. Among counties in the top HIV prevalence quintile, drive time to care is six-folder higher for rural versus super-urban counties. Counties in the top HIV prevalence quintiles for non-Hispanic Blacks and for Hispanics have >50% longer drive time to care versus for non-Hispanic Whites. Including another potential care source-publicly-funded health centers serving low-income populations-could double the number of high-HIV burden counties with drive time ≤30 min, representing nearly 35,000 additional people living with HIV with accessible HIVCCC. Geographic accessibility to HIVCCC is inadequate in the US South, even in high HIV burden areas, and geographic and racial/ethnic disparities exist. Structural factors, such as geographic accessibility to care, may drive disparities in health outcomes. Further research on programmatic policies, and evidence-based alternative HIV care delivery models improving access to care, is critical.

With over 1 million people living with HIV, the US faces national challenges in HIV care delivery due to an inadequate HIV specialist workforce and the increasing role of non-communicable chronic diseases in driving morbidity and mortality in HIV-infected patients. Alternative HIV care delivery models, which include substantial roles for advanced practitioners and/or coordination between specialty and primary care settings in managing HIV-infected patients, may address these needs. We aimed to systematically review the evidence on patient-level HIV-specific and primary care health outcomes for HIV-infected adults receiving outpatient care across HIV care delivery models. We identified randomized trials and observational studies from bibliographic and other databases through March 2016. Eligible studies met pre-specified eligibility criteria including on care delivery models and patient-level health outcomes. We considered all available evidence, including non-experimental studies, and evaluated studies for risk of bias. We identified 3605 studies, of which 13 met eligibility criteria. Of the 13 eligible studies, the majority evaluated specialty-based care (9 studies). Across all studies and care delivery models, eligible studies primarily reported mortality and antiretroviral use, with specialty-based care associated with mortality reductions at the clinician and practice levels and with increased antiretroviral initiation or use at the clinician level but not the practice level. Limited and heterogeneous outcomes were reported for other patient-level HIV-specific outcomes (e.g., viral suppression) as well as for primary care health outcomes across all care delivery models. No studies addressed chronic care outcomes related to aging. Limited evidence was available across geographic settings and key populations. As redesign of care delivery in the US continues to evolve, better understanding of patient-level HIV-related and primary care health outcomes, especially across different staffing models and among different patient populations and geographic locations, is urgently needed to improve HIV disease management.