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Objective. To better understand attributes of ART-associated HIV-induced T-cell responses that might be therapeutically harnessed. Methods. CD8+ T-cell responses were evaluated in some HIV-1 chronically infected participants of the fixed duration STI substudy of the DART trial. Magnitudes, breadths, and functionality of IFN-γ and Perforin responses were compared in STI (n=42) and continuous treatment (CT) (n=46) before and after a single STI cycle when the DART STI trial was stopped early due to inferior clinical outcome in STI participants. Results. STI and CT had comparable magnitudes and breadths of monofunctional CD8+IFNγ+ and CD8+Perforin+ responses. However, STI was associated with significant decline in breadth of bi-functional (CD8+IFNγ+Perforin+) responses; P=.02, Mann-Whitney test. Conclusions. STI in individuals initiated onto ART at

Background: Children under the age of five experience a significant disease burden from diarrheal illnesses. This poses a severe public health risk as the second leading cause of infant death worldwide, after pneumonia. Lira City in Uganda is one of the developing urban areas with limited information about the diarrheal disease among children under the age of 5 years. This study aimed to determine the prevalence and assess the water, sanitation and hygiene related factors associated with diarrheal diseases among children under five years in Lira City., Methods: The study was conducted among 492 care takers of children under the age of 5 years in Lira City between August 2022 and September 2022. Data was collected using an interviewer administered questionnaire and a multi-stage sampling was used to select study participants. Data was analyzed by bivariate and multivariate logistic regression using STATA version 17. P-value of < 0.05 was considered statistically significant., Results: Out of 541 participants, 492 responded. The majority of the respondents, 425(86.4%) were female, 146(29.7%) had children aged 1-12 months, 192 (39%) had primary level education, and 155(31.5%) were self-employed. The prevalence of diarrhea among children under five years was 130(26.4%) and the associated factors with diarrheal disease were children between 49-60 months old (AOR = 0.12, 95% CI: 0.03-0.39, P = 0.001), cleaning the latrine more times (AOR = 0.42, 95% CI: 0.22-0.81, P = 0.010) and not treating water (AOR = 1.84, 95% CI: 1.11-3.06, P = 0.018)., Conclusion: There is high prevalence of diarrhea among children under 5 years of age. The study's findings highlight the need for ongoing efforts to lower the prevalence of diarrheal illnesses among children under the age of five in Uganda's emerging urban areas., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Auma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Some HIV infected individuals remain asymptomatic for protracted periods of time in the absence of antiretroviral therapy (ART). Virological control, CD4 T cell loss and HIV-specific responses are some of the key interrelated determinants of HIV-1 disease progression. In this study, possible interactions between viral load, CD4 T cell slopes, host genetics and HIV-specific IFN-gamma responses were evaluated in chronically HIV-1-infected adults., Methodology/principal Findings: Multilevel regression modeling was used to stratify clade A or D HIV-infected individuals into disease progression groups based on CD4 T cell slopes. ELISpot assays were used to quantify the frequency and magnitude of HIV-induced IFN-gamma responses in 7 defined rapid progressors (RPs) and 14 defined slow progressors (SPs) at a single time point. HLA typing was performed using reference strand conformational analysis (RSCA). Although neither the breadth nor the magnitude of the proteome-wide HIV-specific IFN-gamma response correlated with viral load, slow disease progression was associated with over-representation of host immunogenetic protective HLA B* alleles (10 of 14 SPs compared to 0 of 7; p = 0.004, Fisher's Exact) especially B*57 and B*5801, multiclade Gag T-cell targeting (71%, 10 of 14 SPs compared to 14%, 1 of 7 RPs); p = 0.029, Fisher's Exact test and evident virological control (3.65 compared to 5.46 log10 copies/mL in SPs and RPs respectively); p<0.001, unpaired student's t-test, Conclusions: These data are consistent with others that associated protection from HIV disease with inherent host HLA B allele-mediated ability to induce broader Gag T-cell targeting coupled with apparent virological control. These immunogenetic features of Gag-specific immune response which could influence disease progression may provide useful insight in future HIV vaccine design.

Investigations concerning the extent and nature of subtype-specific and intersubtype immune responses in HIV-1-infected persons are necessary for the development of appropriate candidate vaccines. In the cross-sectional study described here, 26 HIV-1-positive Ugandan patients were tested for their ability to mount HIV antigen-specific cellular immune responses. Subjects were infected with either HIV-1 subtypes A, C, or D. Recombinant vaccinia virus (rVV)-based and peptide-based enzyme-linked immunospot (Elispot) assays were used to evaluate HIV-1-specific gamma-interferon (IFN-gamma) cellular responses. rVV expressing gag, pol, or env proteins derived from HIV-1 subtypes A, B, and D were evaluated for their ability to induce whole HIV-1-protein-specific IFN-gamma responses in 14 patients. A panel of previously identified HLA class I-restricted peptides based on representative sequences from HIV-1 subtypes A, B, C, and D and restricted through HLA-A2, -A29, -B42, -B53, and -B57 alleles were used to evaluate the presence of HIV-1-peptide-specific T cells in 19 patients. Using rVV, 27 of a possible 38 subtype-specific responses (71%) and 56 of a possible 110 intersubtype responses (51%) were observed. When appropriate peptides were used 18 of 39 (46.2%) subtype-specific and 13 of 39 (33.3%) intersubtype responses were observed. Peptide responses were higher quantitatively than those seen when rVV were used. In 7 patients, both rVV and specific peptides were evaluated; in 3 of 7 individuals, global responses were seen despite a lack of measurable HLA-restricted peptide-specific responses demonstrating the need to evaluate a broader range of HIV-specific immune responses.