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Permanent URI for this collectionhttps://pubs.cidrz.org/handle/123456789/12455
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Item Diagnostic value of serological scores for the detection of liver steatosis in people with HIV in low- and middle-income countries.(2026-May-01) Plaisy MK; Mondoka C; Moreira R; Samala N; Borse R; Kuniholm MH; Minga A; Wandeler G; Lopez-Iñiguez A; Michael D; Ross J; Shumbusho F; Mensah E; Shamu T; Crabtree-Ramirez BE; Byakwaga H; Rupasinghe D; Murenzi G; Mureithi F; Diero L; Mivumbi JP; Nguyen DTH; Maruri F; Jaquet A; Perazzo HBACKGROUND: The accuracy of Fatty Liver Index (FLI) and Hepatic Steatosis Index (HSI) to predict liver steatosis in people with HIV (PWH) remains poorly studied in low- and middle-income countries (LMICs). We assessed their diagnostic performances in a multiregional cohort. METHODS: This cross-sectional analysis included PWH aged ≥40 years on antiretroviral therapy for ≥6 months at enrolment (2020-2023) in the Sentinel Research Network (SRN) of IeDEA consortium, across 12 HIV clinics in Asia-Pacific, Americas, and central, East, southern, and West Africa regions. Liver steatosis was defined based on Controlled Attenuation Parameter (CAP) ≥248 dB/m using vibration-controlled transient elastography. HSI was evaluated in the overall population, while FLI was assessed and compared to HSI in a subset of participants with available data. Model discrimination was assessed using area under the receiver operating characteristic curve (AUROC) and model calibration with calibration plots. A decision curve analysis was performed to compare their clinical utility. RESULTS: Among 2195 PWH assessed using CAP, 624 (28.4%) presented with liver steatosis. HSI showed acceptable discriminative ability (AUROC = 0.74) but poor calibration, generally overestimating the risk, except in Asia-Pacific region. FLI performed better than HSI (AUROC = 0.80, P < 0.001), and demonstrated good calibration except in sub-Saharan Africa. Both scores showed high clinical utility, with FLI demonstrating a greater net benefit when compared with HSI. CONCLUSION: FLI demonstrated higher accuracy and clinical utility within a subgroup of regions. However, the limited performance of FLI and HSI in sub-Saharan populations highlights the need to adapt existing tools or develop new predictive models tailored to regional contexts.Item Novel integrase mutations linked to genotypic DTG resistance in African non-B HIV-1 strains: the DTG RESIST study.(2026-Mar-04) Han N; Loosli T; Sauermann M; Çelikağ İ; Anderegg N; Baye BC; Bolton Moore C; Buzaalirwa L; Byakwaga H; Chimbetete C; Ebasone PV; Goodrich S; Huwa J; Kasozi C; Mafoua A; Massamba AC; Messou E; Minga A; Murenzi G; Muula G; Muyindike W; Naidoo SJ; Nsonde DM; Poda AG; Ramdé R; Semeere A; Singh L; Günthard HF; Egger M; Giandhari J; Lessells R; Kouyos RDBACKGROUND: Integrase mutations associated with dolutegravir resistance have been well characterized, but based on limited data from non-B subtypes. OBJECTIVES: We aim to identify potential integrase mutations not currently classified as integrase strand transfer inhibitor (INSTI) resistance mutations (DRMs) in individuals with viremia on dolutegravir-based regimens. METHODS: We included integrase sequences from DTG RESIST study sites in African countries. These were interpreted using Stanford HIVdb v9.8. We used a viral genome-wide association study-like approach restricted to the integrase region (INT-WAS) to identify mutations not classified as major or accessory INSTI DRMs but occurring more frequently in sequences carrying major INSTI DRMs than in those without major INSTI DRMs. We performed the same INT-WAS analysis with drug-naïve sequences from the Los Alamos HIV-1 database to test whether these identified mutations were enriched among sequences from individuals with viraemia whilst receiving DTG-based treatment. RESULTS: Among 382 sequences, 104 (27.2%) showed at least intermediate dolutegravir resistance. Twelve integrase mutations not classified as major or accessory DRMs (S39R, L45I, I72L, L74I, V79I, I113V, S119R, K156N, I208M, T218M, A265V, and R284G) were significantly associated with predicted DTG resistance. Among them, V79I [adjusted odds ratio (aOR) 167.1, 95% credible interval (CrI) 17.9-2947.6] and I72L (aOR 65.6, 95% CrI 6.6-1273.7) were strongly associated. S39R, L45I, V79I, S119R, and K156N were linked to established INSTI resistance pathways, and I72L, L74I, V79I, K156N, I208M, and R284G were overrepresented in sequences from viraemic individuals on DTG-based treatment relative to drug-naïve sequences. CONCLUSIONS: We identified several amino acid substitutions outside the established DRMs that are strongly associated with predicted dolutegravir resistance. Dolutegravir resistance evolution is complex and likely involves mutations not currently classified as DRMs.