Browsing by Author "Bbosa, Nicholas"

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    HIV subtype diversity worldwide
    (Current Opinion in HIV and AIDS, 2019) Bbosa, Nicholas; Ssemwanga, Deogratius; Kaleebu, Pontiano
    To provide a summary of the current data on the global HIV subtype diversity and distribution by region. HIV is one of the most genetically diverse pathogens due to its high-mutation and recombination rates, large population size and rapid replication rate. This rapid evolutionary process has resulted in several HIV subtypes that are heterogeneously globally distributed. Recent findings Subtype A remains the most prevalent strain in parts of East Africa, Russia and former Soviet Union countries; subtype B in Europe, Americas and Oceania; subtype C in Southern Africa and India; CRF01_AE in Asia and CRF02_AG in Western Africa. Recent studies based on near full-length genome sequencing highlighted the growing importance of recombinant variants and subtype C viruses. The dynamic change in HIV subtype distribution presents future challenges for diagnosis, treatment and vaccine design and development. An increase in recombinant viruses suggests that coinfection and superinfection by divergent HIV strains has become more common necessitating continuous surveillance to keep track of the viral diversity. Cheaper near full-length genome sequencing approaches are critical in improving HIV subtype estimations. However, missing subtype data and low sequence sampling levels are still a challenge in some geographical regions.
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    QuasiFlow: A Nextflow Pipeline for Analysis of NGS-based HIV-1 Drug Resistance Data
    (Bioinformatics advances, 2022) Ssekagiri, Alfred; Jjingo, Daudi; Lujumba, Ibra; Bbosa, Nicholas; Bugembe, Daniel L.; Kateete, David P.; Kaleebu, Pontiano; Ssemwanga, Deogratius
    Next-generation sequencing (NGS) enables reliable detection of resistance mutations in minority variants of human immunodeficiency virus type 1 (HIV-1). There is paucity of evidence for the association of minority resistance to treatment failure, and this requires evaluation. However, the tools for analyzing HIV-1 drug resistance (HIVDR) testing data are mostly web-based which requires uploading data to webservers. This is a challenge for laboratories with internet connectivity issues and instances with restricted data transfer across networks. We present QuasiFlow, a pipeline for reproducible analysis of NGS-based HIVDR testing data across different computing environments. Since QuasiFlow entirely depends on command-line tools and a local copy of the reference database, it eliminates challenges associated with uploading HIV-1 NGS data onto webservers. The pipeline takes raw sequence reads in FASTQ format as input and generates a user-friendly report in PDF/HTML format. The drug resistance scores obtained using QuasiFlow were 100% and 99.12% identical to those obtained using web-based HIVdb program and HyDRA web respectively at a mutation detection threshold of 20%.
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    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, Deogratius
    We 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.