Kappelkearns8199

Associations between markers of liver and renal dysfunction and nucleotide reverse transcriptase inhibitor plasma exposure are ill-defined. BMS-536924 As part of a large cohort study (Pharmacokinetic and Clinical Observations in People over Fifty), we analysed associations between alanine aminotransferase and estimated glomerular filtration rate results in people living with HIV on tenofovir disoproxil fumarate, emtricitabine, abacavir and lamivudine. While we found no associations between nucleotide reverse transcriptase inhibitor concentrations and alanine aminotransferase, lower estimated glomerular filtration rate values were associated with greater tenofovir, emtricitabine and lamivudine exposure, whereas abacavir showed no associations.OBJECTIVE To evaluate the impact of the 12 January 2010 earthquake on HIV cases from Haiti's national HIV surveillance system and assess the characteristics of people living with HIV 1-year before and after the earthquake. DESIGN An interrupted time-series design and cross-sectional analysis. METHODS We used autoregressive integrated moving average structures to model abrupt changes to the monthly, incident HIV case counts from HIV care clinics as reported to the Haitian Active Longitudinal Tracking of HIV System (French acronym SALVH) by clinical networks (n = 3) and earthquake instrumental intensity zones (n = 4). Preearthquake and postearthquake differences in patient-level characteristics including clinical values were examined using the χ test, t tests, Wilcoxon rank-sum test. RESULTS In the month immediately following the earthquake, all three clinical networks experienced statistically significant declines in cases reported iSanté (-31.4%), Groupe Haïtien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (-29.9%) and Zamni Lasante (-32.2%). Zone 8 (the most severe) was the only area with a statistically significant decline (-45.5%). Of the three clinical networks, only iSanté returned to preearthquake reporting levels by the end of our study period. Patient-level characteristics did not change dramatically after the earthquake. CONCLUSION Despite case reporting declines, especially in clinics near the earthquake epicenter, SALVH remained intact with less impact than expected. This national system is a critical component of Haiti's strategic health information system initiative and plays a central role to HIV monitoring and evaluation efforts.OBJECTIVES A previous meta-analysis reported high HIV incidence among pregnant and breast-feeding women in sub-Saharan Africa (SSA), but limited evidence of elevated risk of HIV acquisition during pregnancy or breast-feeding when compared with nonpregnant periods. The rapidly evolving HIV prevention and treatment landscape since publication of this review may have important implications for maternal HIV incidence. DESIGN Systematic review and meta-analysis. METHODS We searched four databases and abstracts from relevant conferences through 1 December 2018, for literature on maternal HIV incidence in SSA. We used random-effects meta-analysis to summarize incidence rates and ratios, and to estimate 95% prediction intervals. We evaluated potential sources of heterogeneity with random-effects meta-regression. RESULTS Thirty-seven publications contributed 100 758 person-years of follow-up. The estimated average HIV incidence rate among pregnant and breast-feeding women was 3.6 per 100 person-years (95% prediction interval 1.2--11.1), while the estimated average associations between pregnancy and risk of HIV acquisition, and breast-feeding and risk of HIV acquisition, were close to the null. Wide 95% prediction intervals around summary estimates highlighted the variability of HIV incidence across populations of pregnant and breast-feeding women in SSA. Average HIV incidence appeared associated with age, partner HIV status, and calendar time. Average incidence was highest among studies conducted pre-2010 (4.1/100 person-years, 95% prediction interval 1.1--12.2) and lowest among studies conducted post-2014 (2.1/100 person-years, 95% prediction interval 0.7--6.5). CONCLUSION Substantial HIV incidence among pregnant and breast-feeding women in SSA, even in the current era of combination HIV prevention and treatment, underscores the need for prevention tailored to high-risk pregnant and breast-feeding women.OBJECTIVE To investigate long-term persistence of HIV-specific lymphocyte immunity in perinatally HIV-infected children treated within the first year of life. DESIGN Twenty perinatally HIV-infected children who received ART therapy within the first year of life (early treated) and with stable viral control (>5 years) were grouped according to their serological response to HIV. METHODS Western blot analysis and ELISA defined 14 HIV-seropositive and six seronegative patients. Frequencies of gp140-specific T-cell and B-cell, and T-cell cytokine production were quantified by flow cytometry in both seronegatives and seropositives. Transcriptional signatures in purified gp140-specific B-cell subsets, in response to in-vitro stimulation with HIV peptides was evaluated by multiplex RT-PCR. RESULTS Gp140-specific T cells and B cells persist at similar levels in both groups. A higher production of IL-21 in gp140-specific T cells was found in seropositives vs. seronegatives (P = 0.003). Gene expression in switched IgM-IgD- gp140-specific memory B cells after stimulation with HIV peptides in vitro demonstrated a differential expression of genes involved in signal transduction and activation after BCR/TLR triggering and B-cell activation. Genes relating to antibody production (PRDM1) and T-B cognate stimulation (CXCR4, IL21R) were differentially induced after in-vitro stimulation in seronegatives vs. seropositives suggesting a truncated process of B-cell maturation. CONCLUSION HIV-specific memory B and T cells persist in early treated regardless their serological status. Seronegatives and seropositives are distinguished by gp140-specific T-cell function and by distinct transcriptional signatures of gp140-specific B cells after in-vitro stimulation, presumably because of a different antigen exposure. Such qualitative insights may inform future immunotherapeutic interventions.