Browsing by Author "Kapaata, Anne"
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Item Infection with HIV-1 subtype D among Acutely Infected Ugandans is Associated with Higher Median Concentration of Cytokines Compared to Subtype(IJID Regions, 2022) Kapaata, Anne; Balinda, Sheila N.; Kikaire, Bernard; Egesa, Moses; Lubyayi, Lawrence; Macharia, Gladys N.; Kamali, Anatoli; Gilmour, Jill; Bagaya, Bernard; Salazar-Gonzalez, Jesus F.; Kaleebu, PontianoThe observation that HIV-1 subtype D progresses faster to disease than subtype A prompted us to examine cytokine levels early after infection within the predominant viral subtypes that circulate in Uganda and address the following research questions: (1) Do cytokine levels vary between subtypes A1 and D? (2) Do cytokine profiles correlate with disease outcomes? To address these questions, HIV-1 subtypes were determined by population sequencing of the HIV-1 pol gene and 37 plasma cytokine concentrations were evaluated using V-Plex kits on Meso Scale Discovery platform in 65 recent sero-converters. HIV-1 subtype D (pol) infections exhibited significantly higher median plasma concentrations of IL-5, IL-16, IL-1α, IL-7, IL-17A, CCL11 (Eotaxin-1), CXCL10 (IP-10), CCL13 (MCP-4) and VEGF-D compared to subtype A1 (pol) infections. We also found that IL-12/23p40 and IL-1α were associated with faster CD4+T cell count decline, while bFGF was associated with maintenance of CD4+ counts above 350 cells/microliter. Our results suggest that increased production of cytokines in early HIV infection may trigger a disruption of the immune environment and contribute to pathogenic mechanisms underlying the accelerated disease progression seen in individuals infected with HIV-1 subtype D in Uganda.Item Rates Of HIV-1 Virological Suppression And Patterns Of Acquired Drug Resistance Among Fisherfolk On First-Line Antiretroviral Therapy In Uganda(Journal of Antimicrobial Chemotherapy, 2019) Omooja, Jonah; Nannyonjo, Maria; Sanyu, Grace; Nabirye, Stella E.; Nassolo, Faridah; Lunkuse, Sandra; Kapaata, Anne; Segujja, Farouk; Kateete, David Patrick; Ssebaggala, Eric; Bbosa, Nicholas; Aling, Emmanuel; Nsubuga, Rebecca N.; Kaleebu, Pontiano; Ssemwanga, DeogratiusWe examined virological outcomes, patterns of acquired HIV drug resistance (ADR), correlates of virological failure (VF) and acquired drug resistance among fisherfolk on first-line ART.We enrolled 1169 adults on ART for a median duration of 6, 12, 24, 36 and ≥48 months and used a pooled VL testing approach to identify VF (VL ≥1000 copies/mL). We performed genotyping among VF cases and determined correlates of VF and ADR by logistic regression.The overall virological suppression rate was 91.7% and ADR was detected in 71/97 (73.2%) VF cases. The most prevalent mutations were M184V/I (53.6%) for NRTIs and K103N (39.2%) for NNRTIs. Thymidine analogue mutations were detected in 21.6% of VF cases while PI mutations were absent. A zidovudine-based ART regimen, duration on ART (≥24 months) and secondary/higher education level were significantly associated with VF. A nevirapine-based regimen [adjusted OR (aOR): 1.87; 95% CI: 0.03–0.54)] and VL ≥10000 copies/mL (aOR: 3.48; 95% CI: 1.37–8.85) were ADR correlates. The pooling strategies for VL testing with a negative predictive value (NPV) of ≥95.2% saved US $20320 (43.5%) in VL testing costs.We observed high virological suppression rates among these highly mobile fisherfolk; however, there was widespread ADR among those with VF at the first VL testing prior to intensive adherence counselling. Timely treatment switching and adherence support is recommended for better treatment outcomes. Adoption of pooled VL testing could be cost effective, particularly in resource-limited settings.