AIDS
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Randomized Controlled Trial
Safety and immunogenicity of the M72/AS01 candidate tuberculosis vaccine in HIV-infected adults on combination antiretroviral therapy: a phase I/II, randomized trial.
Tuberculosis (TB) is highly prevalent among HIV-infected people, including those receiving combination antiretroviral therapy (cART), necessitating a well tolerated and efficacious TB vaccine for these populations. We evaluated the safety and immunogenicity of the candidate TB vaccine M72/AS01 in adults with well controlled HIV infection on cART. ⋯ M72/AS01 was clinically well tolerated and immunogenic in this population, supporting further clinical evaluation in HIV-infected individuals in TB-endemic settings.
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There is intense interest in the role of programmed death 1 (PD-1) in causing persistent T-cell dysfunction in HIV infection. However, the impact of HIV infection and antiretroviral treatment (ART) on the expression of PD-1 on T cells is still poorly defined. ⋯ Across two large cohorts of untreated and treated individuals, we found consistent associations between HIV RNA levels, CD8⁺ T-cell activation and PD-1 expression on CD8⁺ T cells. In contrast, CD4⁺ T-cell counts and CD4⁺ T-cell activation were more consistent correlates of PD-1 expression on CD4⁺ T cells. PD-1 expression appears to be driven by both direct antigen and homeostatic pathways.
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Antiretroviral therapy (ART) has been implicated in bone loss in HIV. The role of inflammation and vitamin D is unclear and better investigated in ART-naive individuals. ⋯ BMD at the total hip and trochanter sites decreased in the HIV-infected, ART-naive adults, but not controls, over this 48-week study. Higher serum interleukin-6 concentrations were associated with progression to osteopenia or osteoporosis status in the HIV-infected group.
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Sub-Saharan Africa has large populations of HIV-infected parents who need support to raise their HIV-uninfected children. This research evaluates the 'Amagugu Intervention' aimed at supporting mothers to disclose their own HIV diagnosis to their HIV-uninfected children. ⋯ This intervention is acceptable in resource-limited settings and shows promise. Further research using a controlled design is needed to test this intervention.
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Observational Study
In-utero exposure to maternal HIV infection alters T-cell immune responses to vaccination in HIV-uninfected infants.
In sub-Saharan Africa, HIV-exposed uninfected (HEU) infants have higher morbidity and mortality than HIV-unexposed infants. To evaluate whether immune dysfunction contributes to this vulnerability of HEU infants, we conducted a longitudinal, observational cohort study to assess T-cell immune responses to infant vaccines (Mycobacterium bovis BCG and acellular pertussis) and staphylococcal enterotoxin B (SEB). In total, 46 HEU and 46 HIV-unexposed infants were recruited from Khayelitsha, Cape Town. ⋯ These data show for the first time, when adjusting for confounders, that exposure to HIV in utero is associated with significant alterations to CD4 and CD8T-cell immune responses in infants to vaccines and nonspecific antigens.