The impact of extended use of ART in developing countries has been enormous. A thorough understanding of all factors contributing to the success of antiretroviral therapy is required. The current study aims to investigate the value of cross-sectional drug resistance monitoring using DNA and RNA oligonucleotide ligation assays (OLA) in treatment cohorts in low-resource settings. The study was conducted in the first cohort of children gaining access to structured ART in Peru.
The viral and host factors involved in transmission of HIV through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations. To evaluate the viral and immunological factors directly related to milk transmission of virus, we have evaluated the disease course of Simian Immunodeficiency Virus (SIV) in lactating rhesus macaques (Macaca mulatta) as a model of natural breast milk transmission of HIV. Fourteen lactating macaques were infected intravenously with SIV/DeltaB670, a pathogenic isolate of SIV and were pair-housed with their suckling infants throughout the disease course. Transmission was observed in 10 mother-infant pairs over a one-year period. Two mothers transmitted virus during the period of initial viremia 14–21 days post inoculation (p.i.) and were classified as early transmitters. Peak viral loads in milk and plasma of early transmitters were similar to other animals, however the early transmitters subsequently displayed a rapid progressor phenotype and failed to control virus expression as well as other animals at 56 days p.i. Eight mothers were classified as late transmitters, with infant infection detected at time points in the chronic stage of the maternal SIV disease course (81 to 360 days). Plasma viral loads, CD4+ T cell counts and SIV-specific antibody titers were similar in late transmitters and non-transmitters. Late breast milk transmission, however, was correlated with higher average milk viral loads and more persistent viral expression in milk 12 to 46 weeks p.i. as compared to non-transmitters. Four mothers failed to transmit virus, despite disease progression and continuous lactation. These studies validate the SIV-infected rhesus macaque as a model for breast milk transmission of HIV. As observed in studies of HIV-infected women, transmission occurred at time points throughout the period of lactation. Transmission during the chronic stage of SIV-infection correlated with a threshold level of virus expression as well as more persistent shedding in milk. This model will be a valuable resource for deciphering viral and host factors responsible for transmission of HIV through breastfeeding.
Abstract: The populations at risk for HIV infection, as well as those living with HIV, overlap with populations that engage in heavy alcohol consumption. Alcohol use has been associated with high-risk sexual behavior and an increased likelihood of acquiring HIV, as well as poor outcome measures of disease such as increased viral loads and declines in CD4+ T lymphocytes among those living with HIV-infections. It is difficult to discern the biological mechanisms by which alcohol use affects the virus:host interaction in human populations due to the numerous variables introduced by human behavior. The rhesus macaque infected with simian immunodeficiency virus has served as an invaluable model for understanding HIV disease and transmission, and thus, provides an ideal model to evaluate the effects of chronic alcohol use on viral infection and disease progression in a controlled environment. In this review, we describe the different macaque models of chronic alcohol consumption and summarize the studies conducted with SIV and alcohol. Collectively, they have shown that chronic alcohol consumption results in higher levels of plasma virus and alterations in immune cell populations that potentiate SIV replication. They also demonstrate a significant impact of chronic alcohol use on SIV-disease progression and survival. These studies highlight the utility of the rhesus macaque in deciphering the biological effects of alcohol on HIV disease. Future studies with this well-established model will address the biological influence of alcohol use on susceptibility to HIV, as well as the efficacy of anti-retroviral therapy.