Browsing by Author "Ssemwanga, Deogratius"

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    HIV drug resistance among adults initiating antiretroviral therapy in Uganda
    (Journal of Antimicrobial Chemotherapy, 2021) Watera, Christine; Ssemwanga, Deogratius; Namayanja, Grace; Asio, Juliet; Lutalo, Tom; Namale, Alice; Sanyu, Grace; Ssewanyana, Isaac; Gonzalez-Salazar, Jesus Fidel; Nazziwa, Jamirah; Nanyonjo, Maria; Raizes, Elliot; Kabuga, Usher; Mwangi, Christina; Kirungi, Wilford; Musinguzi, Joshua; Mugagga, Kaggwa; Katongole Mbidde, Edward; Kaleebu, Pontiano
    WHO revised their HIV drug resistance (HIVDR) monitoring strategy in 2014, enabling countries to generate nationally representative HIVDR prevalence estimates from surveys conducted using this methodology. In 2016, we adopted this strategy in Uganda and conducted an HIVDR survey among adults initiating or reinitiating ART. Methods: A cross-sectional survey of adults aged 18 years initiating or reinitiating ART was conducted at 23 sites using a two-stage cluster design sampling method. Participants provided written informed consent prior to enrolment. Whole blood collected in EDTA vacutainer tubes was used for preparation of dried blood spot (DBS) specimens or plasma. Samples were shipped from the sites to the Central Public Health Laboratory (CPHL) for temporary storage before transfer to the Uganda Virus Research Institute (UVRI) for genotyping. Prevalence of HIVDR among adults initiating or reinitiating ART was determined.
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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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    HIV-1 superinfection can occur in the presence of broadly neutralizing antibodies
    (Vaccine, 2018) Serwanga, Jennifer; Ssemwanga, Deogratius; Muganga, Michael; Nakiboneka, Ritah; Nakubulwa, Susan; Kiwuwa-Muyingo, Sylvia; Morris, Lynn; Redd, Andrew D.; Quinn, Thomas C.; Kaleebu, Pontiano
    Superinfection of individuals already infected with HIV-1 suggests that pre-existing immune responses may not adequately protect against re-infection. We assessed high-risk female sex workers initially infected with HIV-1 clades A, D or A/D recombinants, to determine if HIV-1 broadly neutralizing antibodies were lacking prior to superinfection. Methods: Six superinfected female sex workers previously stratified by HIV-1 high-risk behavior, infecting virus clade and volunteer CD4 counts were evaluated at baseline (n = 5) and at 350 days post-superinfection (n = 6); one superinfected volunteer lacked pre-superinfection plasma. Retrospective plasmas were assessed for neutralization of a multi-clade panel of 12 HIV-1 viruses before superinfection, and then at quarterly intervals thereafter. Similarly stratified singly infected female sex workers were correspondingly assessed at baseline (n = 19) and 350 days after superinfection (n = 24). Neutralization of at least 50% of the 12 viruses (broad neutralization), and geometric means of the neutralization titers (IC50) were compared before and after superinfection; and were correlated with the volunteer HIV-1 superinfection status, CD4 counts, and pseudovirus clade. Results: Preexisting broad neutralization occurred in 80% (4/5) of the superinfected subjects with no further broadening by 350 days after superinfection. In one of the five subjects, HIV-1 superinfection occurred when broad neutralization was lacking; with subsequent broadening of neutralizing antibodies occuring within 9 months and plateauing by 30 months after detection of superinfection. Clade B and C pseudoviruses were more sensitive to neutralization (13; [87%]); and (12; [80%]) than the locally circulating clades A (10; [67%]) and D (6; [40%]), respectively (p = 0.025). Low antibody titers correlated with clade D viruses and with >500 CD4 T cell counts, but not with the superinfection status. Conclusion: These data demonstrate that HIV-1 superinfection can occur both in the presence, and in the absence of broadly neutralizing antibodies.
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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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    The rates of HIV-1 superinfection and primary HIV-1 infection are similar in female sex workers in Uganda
    (Theoretical Medicine and Bioethics, 2008) Redd, Andrew D.; Ssemwanga, Deogratius; Vandepitte, Judith; Wendel, Sarah K.; Ndembi, Nicaise; Bukenya, Justine; Nakubulwa, Susan; Grosskurth, Heiner; Parry, Chris M.; Martens, Craig; Bruno, Daniel; Porcella, Stephen F.; Quinn, Thomas C.; Kaleebu, Pontiano
    To determine and compare the rates of HIV superinfection and primary HIV infection in high-risk female sex workers in Kampala, Uganda. Design—A retrospective analysis of individuals who participated in a clinical cohort study among high-risk female sex workers in Kampala, Uganda. Methods—Plasma samples from HIV-infected female sex workers (FSW) in Kampala, Uganda were examined with next-generation sequencing of the p24 and gp41HIV genomic regions for the occurrence of superinfection. Primary HIV incidence was determined from initially HIV-uninfected FSW from the same cohort, and incidence rate ratios were compared. Results—The rate of superinfection in these women (7/85; 3.4/100py) was not significantly different from the rate of primary infection in the same population (3.7/100py; IRR=0.91, p=0.42). Seven women also entered the study dual infected (16.5% either dual or superinfected). The women with any presence of dual infection were more likely to report sex work as their only source of income (p=0.05), and trended to be older and more likely to be widowed (p=0.07). Conclusions—In this cohort of female sex workers, HIV superinfection occurred at a high rate and was similar to that of primary HIV infection. These results differ from a similar study of high-risk female bar-workers in Kenya that found the rate of superinfection to be significantly lower than the rate of primary HIV infection.
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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.
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    Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross sectional study
    (Sexually transmitted infections, 2019) Namale, Gertrude; Kamacooko, Onesmus; Bagiire, Daniel; Mayanja, Yunia; Abaasa, Andrew; Kilembe, William; Price, Matt; Ssemwanga, Deogratius; Lunkuse, Sandra; Nanyonjo, Maria; Ssenyonga, William; Mayaud, Philippe; Newton, Rob; Kaleebu, Pontiano; Seeley, Janet
    We assessed the prevalence and risk factors associated with virological failure among female sex workers living with HIV on antiretroviral therapy (ART ) in Kampala, Uganda. Methods We conducted a cross-sectional study between January 2015 and December 2016 using routinely collected data at a research clinic providing services to women at high risk of STIs including HIV. Plasma samples were tested for viral load from HIVseropositive women aged ≥18 years who had been on ART for at least 6 months and had received adherence counselling. Samples from women with virological failure (≥1000 copies/mL) were tested for HIV drug resistance by population-based sequencing. We used logistic regression to identify factors associated with virological failure. Results Of 584 women, 432 (74%) with a mean age of 32 (SD 6.5) were assessed, and 38 (9%) were found to have virological failure. HIV resistance testing was available for 78% (28/38), of whom 82.1% (23/28) had at least one major drug resistance mutation (DRM), most frequently M184V (70%, 16/23) and K103N (65%, 15/23). In multivariable analysis, virological failure was associated with participant age 18–24 (adjusted OR (aOR)=5.3, 95% CI 1.6 to 17.9), self-reported ART nonadherence (aOR=2.6, 95% CI 1.2 to 5.8) and baseline CD4+ T-cell count ≤350 cells/mm3 (aOR=3.1, 95% CI 1.4 to 7.0). Conclusions A relatively low prevalence of virological failure but high rate of DRM was found in this population at high risk of transmission. Younger age, self-reported ART non-adherence and low CD4+ T-cell count on ART initiation were associated with increased risk of virological failure.