Suchergebnisse

BackgroundThe degree of immune reconstitution achieved in response to suppressive ART is associated with baseline individual characteristics, such as pre‐treatment CD4 count, levels of viral replication, cellular activation, choice of treatment regimen and gender. However, the combined effect of these variables on long‐term CD4 recovery remains elusive, and no single variable predicts treatment response. We sought to determine if adiposity and molecules associated with lipid metabolism may affect the response to ART and the degree of subsequent immune reconstitution, and to assess their ability to predict CD4 recovery.MethodsWe studied a cohort of 69 (48 females and 21 males) HIV‐infected, treatment‐naïve South African subjects initiating antiretroviral treatment (d4T, 3Tc and lopinavir/ritonavir). We collected information at baseline and six months after viral suppression, assessing anthropometric parameters, dual energy X‐ray absorptiometry and magnetic resonance imaging scans, serum‐based clinical laboratory tests and whole blood‐based flow cytometry, and determined their role in predicting the increase in CD4 count in response to ART.ResultsWe present evidence that baseline CD4+ T cell count, viral load, CD8+ T cell activation (CD95 expression) and metabolic and anthropometric parameters linked to adiposity (LDL/HDL cholesterol ratio and waist/hip ratio) significantly contribute to variability in the extent of CD4 reconstitution (ΔCD4) after six months of continuous ART.ConclusionsOur final model accounts for 44% of the variability in CD4+ T cell recovery in virally suppressed individuals, representing a workable predictive model of immune reconstitution.

AbstractIntroductionThe International AIDS Society convened a multidisciplinary committee of experts in December 2020 to provide guidance and key considerations for the safe and ethical management of clinical trials involving people living with HIV (PLWH) during the SARS‐CoV‐2 pandemic. This consultation did not discuss guidance for the design of prevention studies for people at risk of HIV acquisition, nor for the programmatic delivery of antiretroviral therapy (ART).DiscussionThere is strong ambition to continue with HIV research from both PLWH and the research community despite the ongoing SARS‐CoV‐2 pandemic. How to do this safely and justly remains a critical debate. The SARS‐CoV‐2 pandemic continues to be highly dynamic. It is expected that with the emergence of effective SARS‐CoV‐2 prevention and treatment strategies, the risk to PLWH in clinical trials will decline over time. However, with the emergence of more contagious and potentially pathogenic SARS‐CoV‐2 variants, the effectiveness of current prevention and treatment strategies may be compromised. Uncertainty exists about how equally SARS‐CoV‐2 prevention and treatment strategies will be available globally, particularly for marginalized populations, many of whom are at high risk of reduced access to ART and/or HIV disease progression. All of these factors must be taken into account when deciding on the feasibility and safety of developing and implementing HIV research.ConclusionsIt can be assumed for the foreseeable future that SARS‐CoV‐2 will persist and continue to pose challenges to conducting clinical research in PLWH. Guidelines regarding how best to implement HIV treatment studies will evolve accordingly. The risks and benefits of performing an HIV clinical trial must be carefully evaluated in the local context on an ongoing basis. With this document, we hope to provide a broad guidance that should remain viable and relevant even as the nature of the pandemic continues to develop.

BackgroundAdvanced HIV infection can result in lipoatrophy and wasting, even in the absence of ongoing opportunistic infections, suggesting that HIV may directly affect adipose tissue amount and distribution.MethodsWe assessed the relationship of fat (measured using anthropometry, DEXA, MRI scans) or markers related to glucose and lipid metabolism with viral load in a cross‐sectional sample of 83 antiretroviral‐naïve HIV‐1‐infected South African women. A multivariable linear model was fitted to log10VL to assess the combined effect of these variables.ResultsIn addition to higher T cell activation, women with viral load greater than the population median had lower waist circumference, body mass index and subcutaneous abdominal fat, as well as lower serum leptin. We demonstrate that leptin serum levels are inversely associated with viral replication, independent of the amount of adipose tissue. This association is maintained after adjusting for multiple variables associated with disease progression (i.e., cellular activation and innate immunity effector levels).ConclusionsOur results demonstrate that serum leptin levels are inversely associated with viral replication, independent of disease progression: we postulate that leptin may affect viral replication.

Background: HIV transmission can be decreased substantially by reducing the burden of undiagnosed HIV infection and expanding early and consistent use of antiretroviral therapy (ART). Treatment as prevention (TasP) has been proposed as key to ending the HIV epidemic. To activate TasP in high prevalence countries, like South Africa, communities must be motivated to know their status, engage in care, and remain in care. Community mobilization (CM) has the potential to significantly increase uptake testing, linkage to and retention in care by addressing the primary social barriers to engagement with HIV care-including poor understanding of HIV care; fear and stigma associated with infection, clinic attendance and disclosure; lack of social support; and gender norms that deter men from accessing care. Methods/design: Using a cluster randomized trial design, we are implementing a 3-year-theory-based CM intervention and comparing gains in HIV testing, linkage, and retention in care among individuals residing in 8 intervention communities to that of individuals residing in 7 control communities. Eligible communities include 15 villages within a health and demographic surveillance site (HDSS) in rural Mpumalanga, South Africa, that were not exposed to previous CM efforts. CM activities conducted in the 8 intervention villages map onto six mobilization domains that comprise the key components for community mobilization around HIV prevention. To evaluate the intervention, we will link a clinic-based electronic clinical tracking system in all area clinics to the HDSS longitudinal census data, thus creating an open, population-based cohort with over 30,000 18-49-year-old residents. We will estimate the marginal effect of the intervention on individual outcomes using generalized estimating equations. In addition, we will evaluate CM processes by conducting baseline and endline surveys among a random sample of 1200 community residents at each time point to monitor intervention exposure and community level change using validated measures of CM. Discussion: Given the known importance of community social factors with regard to uptake of testing and HIV care, and the lack of rigorously evaluated community-level interventions effective in improving testing uptake, linkage and retention, the proposed study will yield much needed data to understand the potential of CM to improve the prevention and care cascade. Further, our work in developing a CM framework and domain measures will permit validation of a CM conceptual framework and process, which should prove valuable for community programming in Africa.