Browsing by Author "Kaleebu, Pontiano"

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    Association between serotonin transporter gene polymorphisms and increased suicidal risk among HIV positive patients in Uganda
    (BMC genetics, 2017) Kalungi, Allan; Seedat, Soraya; Hemmings, Sian M. J.; Merwe, Lize van der; Joloba, Moses L.; Nanteza, Ann; Nakassujja, Noeline; Birabwa, Harriet; Serwanga, Jennifer; Kaleebu, Pontiano; Kinyanda, Eugene
    Persons living with HIV/AIDS (PLWHA) are at an increased risk of suicide. Increased suicidal risk is a predictor of future attempted and completed suicides and has been associated with poor quality of life and poor adherence with antiretroviral therapy. Clinical risk factors have low predictive value for suicide, hence the interest in potential neurobiological correlates and specific heritable markers of suicide vulnerability. The serotonin transporter gene has previously been implicated in the aetiology of increased suicidal risk in non-HIV infected study populations and its variations may provide a platform for identifying genetic risk for suicidality among PLWHA. The present cross-sectional study aimed at identifying two common genetic variants of the serotonin transporter gene and their association with increased suicidal risk among human immunodeficiency virus (HIV)-positive adults in Uganda. Results: The prevalence of increased suicidal risk (defined as moderate to high risk suicidality on the suicidality module of the Mini Neuropsychiatric Interview (M.I.N.I) was 3.3% (95% CI, 2.0–5.3). The 5-HTTLPR was found to be associated with increased suicidal risk before Bonferroni correction (p-value = 0.0174). A protective effect on increased suicidal risk was found for the 5-HTTLPR/rs25531 SA allele (p-value = 0.0046)- which directs reduced expression of the serotonin transporter gene (5-HTT). Conclusion: The SA allele at the 5-HTTLPR/rs25531 locus is associated with increased suicidal risk among Ugandan PLWHA. Further studies are needed to validate this finding in Ugandan and other sub-Saharan samples.
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    Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial
    (Tropical medicine & international health, 2015) Nakanjako, Damalie; Ssinabulya, Isaac; Nabatanzi, Rose; Bayigga, Lois; Kiragga, Agnes; Joloba, Moses; Kaleebu, Pontiano; Kambugu, Andrew D.; Kamya, Moses R.; Sekaly, Rafick; Elliott, Alison; Mayanja-Kizza, Harriet
    T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery.A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry.Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported.Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa.
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    CD32-Expressing CD4 T Cells are Phenotypically Diverse and Can Contain Proviral HIV DNA
    (Frontiers in immunology, 2018) Martin, Genevieve E.; Pace, Matthew; Brown, Helen; Kaleebu, Pontiano; Lwanga, Julianne; Klenerman, Paul; Fox, Julie
    Efforts to both characterize and eradicate the HIV reservoir have been limited by the rarity of latently infected cells and the absence of a specific denoting biomarker. CD32a (FcγRIIa) has been proposed to be a marker for an enriched CD4 T cell HIV reservoir, but this finding remains controversial. Here, we explore the expression of CD32 on CD3+CD4+ cells in participants from two primary HIV infection studies and identify at least three distinct phenotypes (CD32low, CD32+CD14+, and CD32high). Of note, CD4 negative enrichment kits remove the majority of CD4+CD32+ T cells, potentially skewing subsequent analyses if used. CD32high CD4 T cells had higher levels of HLA-DR and HIV co-receptor expression than other subsets, compatible with their being more susceptible to infection. Surprisingly, they also expressed high levels of CD20, TCRαβ, IgD, and IgM (but not IgG), markers for both T cells and naïve B cells. Compared with other populations, CD32low cells had a more differentiated memory phenotype and high levels of immune checkpoint receptors, programmed death receptor-1 (PD-1), Tim-3, and TIGIT. Within all three CD3+CD4+CD32+ phenotypes, cells could be identified in infected participants, which contained HIV DNA. CD32 expression on CD4 T cells did not correlate with HIV DNA or cell-associated HIV RNA (both surrogate measures of overall reservoir size) or predict time to rebound viremia following treatment interruption, suggesting that it is not a dominant biomarker for HIV persistence. Our data suggest that while CD32+ T cells can be infected with HIV, CD32 is not a specific marker of the reservoir although it might identify a population of HIV enriched cells in certain situations.
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    COHORT PROFILE: The Complications of Long‑Term Antiretroviral Therapy study in Uganda (CoLTART), a prospective clinical cohort
    (AIDS research and therapy, 2017-05-04) Mayanja, Billy Nsubuga; Kasamba, Ivan; Namakoola, Ivan; Kazooba, Patrick; Kaleebu, Pontiano; Munderi, Paula
    Antiretroviral therapy (ART) improves the survival and quality of life of HIV-positive individuals, but the effects of long-term ART use do eventually manifest. The Complications of Long-Term Antiretroviral Therapy cohort study in Uganda (CoLTART) was established to investigate the metabolic and renal complications of long-term ART use among Ugandan adults. We describe the CoLTART study set-up, aims, objectives, study methods, and also report some preliminary cross–sectional study enrolment metabolic and renal complications data analysis results.
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    Community‑based ART distribution system can effectively facilitate long‑term program retention and low‑rates of death and virologic failure in rural Uganda
    (AIDS research and therapy, 2015) Okoboi, Stephen; Ding, Erin; Persuad, Steven; Wangisi, Jonathan; Birungi, Josephine; Shurgold, Susan; Kato, Darius; Nyonyintono, Maureen; Egessa, Aggrey; Bakanda, Celestin; Munderi, Paula; Kaleebu, Pontiano; Moore, David M.
    Community-drug distribution point is a care model for stable patients in the community designed to make ART delivery more efficient for the health system and provide appropriate support to encourage long-term retention of patients. We examined program retention among ART program participants in rural Uganda, which has used a community-based distribution model of ART delivery since 2004. Methods: We analyzed data of all patients >18 years who initiated ART in Jinja, Ugandan site of The AIDS Support Organization between January 1, 2004 and July 31, 2009. Participants attended clinic or outreach visits every 2–3 months and had CD4 cell counts measured every 6 months. Retention to care was defined as any patient with at least one visit in the 6 months before June 1, 2013. We then identified participants with at least one visit in the 6 months before June 1, 2013 and examined associations with mortality and lost-to-follow-up (LTFU). Participants with >4 years of follow up during August, 2012 to May, 2013 had viral load conducted, since no routine viral load testing was available. Results: A total of 3345 participants began ART during 2004–2009. The median time on ART in June 2013 was 5.69 years. A total of 1335 (40 %) were residents of Jinja district and 2005 (60 %) resided in outlying districts. Of these, 2322 (69 %) were retained in care, 577 (17 %) died, 161 (5 %) transferred out and 285 (9 %) were LTFU. Factors associated with mortality or LTFU included male gender, [Adjusted Hazard Ratio (AHR) = 1.56; 95 % CI 1.28–1.9], CD4 cell count <50 cells/μL (AHR = 4.09; 95 % CI 3.13–5.36) or 50–199 cells/μL (AHR = 1.86; 95 % CI 1.46–2.37); ART initiation and WHO stages 3 (AHR = 1.35; 95 % CI 1.1–1.66) or 4 (AHR = 1.74; 95 % CI 1.23–2.45). Residence outside of Jinja district was not associated with mortality/LTFU (p value = 0.562). Of 870 participants who had VL tests, 756 (87 %) had VLs <50 copies/mL. Conclusion: Community-based ART distribution systems can effectively mitigate the barriers to program retention and result in good rates of virologic suppression.
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    Durability Of Non-Nucleotide Reverse Transcriptase Inhibitor-Based First-Line ART Regimens After 7 Years Of Treatment In Rural Uganda
    (Medicine, 2021) Nanfuka, Mastula; Forrest, Jamie I.; Zhang, Wendy; Okoboi, Stephen; Birungi, Josephine; Kaleebu, Pontiano; Zhu, Julia; Tibenganas, Samuel; Moore, David M.
    Most antiretroviral therapy (ART) programs in resource-limited settings have historically used non-nucleotide reverse transcriptase inhibitor (NNRTI)-based regimens with limited access to routine viral load (VL) testing. We examined the long-term success of these regimens in rural Uganda among participants with 1 measured suppressed VL. We conducted a prospective cohort study of participants who had been on NNRTI-based first-line regimens for ≥4years and had a VL <1000copies/mL at enrollment in Jinja, Uganda. We collected clinical and behavioral data every 6 months and measured VL again after 3 years. We quantified factors associated with virologic failure (VF) (VL≥1000copies/mL) using Wilcoxon Rank Sum, chisquare, and Fisher’s Exact Tests. We enrolled 503 participants; 75.9% were female, the median age was 45years, and the median duration of time on ART was 6.8 years (IQR=6.0–7.6 years). Sixty-nine percent of participants were receiving nevirapine, lamivudine, and zidovudine regimens; 22.5% were receiving efavirenz, lamivudine, and zidovudine; and 8.6% were receiving other regimens. Of the 479 with complete follow-up data, 12 (2.5%) had VL≥1000copies/mL. VF was inversely associated with reporting never missing pills (41.7% of VFs vs 72.8% non-VFs, P=.034). There were differences in distribution of the previous ART regimens (P=.005), but no clear associations with specific regimens. There was no association between having a VL of 50 to 999copies/mL at enrollment and later VF (P=.160). Incidence of VF among individuals receiving ART for nearly 7 years was very low in the subsequent 3 years. NNRTI-based regimens appear to be very durable among those with good initial adherence.
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    Duration of HIV-1 Viral Suppression on Cessation of Antiretroviral Therapy in Primary Infection Correlates with Time on Therapy
    (PLoS ONE, 2013) Stöhr, Wolfgang; Fidler, Sarah; McClure, Myra; Weber, Jonathan; Cooper, David; Ramjee, Gita; Kaleebu, Pontiano; Tambussi, Giuseppe; Schechter, Mauro; Babiker, Abdel; Phillips, Rodney E.; Porter, Kholoud; Frater, John
    A minority of HIV-1 positive individuals treated with antiretroviral therapy (ART) in primary HIV-1 infection (PHI) maintain viral suppression on stopping. Whether this is related to ART duration has not been explored. Design: And Methods: Using SPARTAC trial data from individuals recruited within 6 months of seroconversion, we present an observational analysis investigating whether duration of ART was associated with post-treatment viraemic control. Kaplan-Meier estimates, logistic regression and Cox models were used. 165 participants reached plasma viral loads (VL) 12 weeks compared to ≤12 weeks (p=0.061). Cumulative probabilities of remaining 12 weeks. In multivariable regression, ART for >12 weeks was independently associated with a lower probability of being ≥400 copies/ml within 12 weeks of ART stop (OR=0.11 (95%CI=0.03,0.34), p
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    Effect of Human Immunodeficiency Virus (HIV) Type 1 Envelope Subtypes A and D on Disease Progression in a Large Cohort of HIV-1–Positive Persons in Uganda
    (The Journal of Infectious Diseases, 2002) Kaleebu, Pontiano; French, Neil; Mahe, Cedric; Yirrell, David; Watera, Christine; Lyagoba, Fred; Nakiyingi, Jessica; Rutebemberwa, Alleluiah; Morgan, Dilys; Weber, Jonathan; Gilks, Charles; Whitworth, Jimmy
    The effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression was investigated in 1045 adults in Uganda. At enrollment and every 6 months, a clinical history, examination, and laboratory investigations that included CD4 cell counts were done. HIV-1 envelope subtype was assessed mainly by peptide serology supplemented by heteroduplex mobility assay and DNA sequencing. A multivariate analysis of survival was performed to assess the prognostic value of HIV-1 subtype on death. A marginal general linear model also determined the effect of subtype on CD4 cell count during follow-up. Subtype D was associated with faster progression to death (relative risk, 1.29; 95% confidence interval, 1.07–1.56; P ¼ .009) and with a lower CD4 cell count during follow-up (P ¼ .001), compared with subtype A, after adjusting for CD4 cell count at enrollment. In Africa, envelope subtype D is associated with faster disease progression, compared with subtype A
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    Effectiveness and Cost‑Effectiveness Of Integrating the Management of Depression into Routine HIV Care in Uganda (the HIV + D trial): A protocol for a cluster‑randomised trial
    (International journal of mental health systems, 2021) Kinyanda, Eugene; Kyohangirwe, Leticia; Mpango, Richard S.; Tusiime, Christine; Ssebunnya, Joshua; Katumba, Kenneth; Tenywa, Patrick; Mugisha, James; Sentongo, Hafsa; Akena, Dickens; Muhwezi, Wilson; Kaleebu, Pontiano; Ssembajjwe, Wilber; Patel, Vikram
    An estimated 8–30 % of people living with HIV (PLWH) have depressive disorders (DD) in sub-Saharan Africa. Of these, the majority are untreated in most of HIV care services. There is evidence from low- and middle- income countries of the effectiveness of both psychological treatments and antidepressant medication for the treatment of DD among PLWH, but no evidence on how these can be integrated into routine HIV care. This protocol describes a cluster-randomised trial to evaluate the effectiveness and cost-effectiveness of the HIV + D model for the integration of a collaborative stepped care intervention for DD into routine HIV care, which we have developed and piloted in Uganda.Forty public health care facilities that provide HIV care in Kalungu, Masaka and Wakiso Districts will be randomly selected to participate in the trial. Each facility will recruit 10–30 eligible PLWH with DD and the total sample size will be 1200. The clusters will be randomised 1:1 to receive Enhanced Usual Care alone (EUC, i.e. HIV clinicians trained in Mental Health Gap Action Programme including guidelines on when and where to refer patients for psychiatric care) or EUC plus HIV + D (psychoeducation, Behavioural Activation, antidepressant medication and referral to a supervising mental health worker, delivered in a collaborative care stepwise approach). Eligibility criteria are PLWH attending the clinic, aged ≥ 18 years who screen positive on a depression screening questionnaire (Patient Health Questionnaire, PHQ-9 ≥ 10). The primary outcome is the mean depressive disorder symptom severity scores (assessed using the PHQ-9) at 3 months’ post-randomisation, with secondary mental health, disability, HIV and economic outcomes measured at 3 and 12 months. The cost-effectiveness of EUC with HIV + D will be assessed from both the health system and the societal perspectives by collecting health system, patient and productivity costs and mean DD severity scores at 3 months, additional to health and non-health related quality of life measures (EQ-5D-5 L and OxCAP-MH).The study findings will inform policy makers and practitioners on the cost-effectiveness of a stepped care approach to integrate depression management in routine care for PLWH in low-resource settings.
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    Estimating the Effect and Cost-Effectiveness of Facemasks in Reducing the Spread of the Severe Acute Respiratory Syndrome- Coronavirus 2 (SARS-CoV-2) in Uganda
    (medRxiv., 2020) Nannyonga, Betty K.; Wanyenze, Rhoda K.; Kaleebu, Pontiano; Ssenkusu, John M.; Lutalo, Tom; Makumbi, Fredrick Edward; Kwizera, Arthur; Byakika, Pauline; Kirungi, Willford; Bosa, Henry Kyobe; Ssembatya, Vincent A.; Mwebesa, Henry; Atwine, Diana; Aceng, Jane Ruth; Woldermariam, Yonas Tegegn
    Evidence that face masks provide effective protection against respiratory infections in the community is scarce. However, face masks are widely used by health workers as part of droplet precautions when caring for patients with respiratory infections. It would therefore be reasonable to suggest that consistent widespread use of face masks in the community could prevent further spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2). In this study we examine public face mask wearing in Uganda where a proportion wears masks to protect against acquiring, and the other to prevent from transmitting SARS-CoV-2. The objective of this study was to determine what percentage of the population would have to wear face masks to reduce susceptibility to and infectivity of SARS-COV-2 in Uganda, keeping the basic reproduction number below unity and/or flattening the curve. We used an SEIAQRD model for the analysis. Results show that implementation of facemasks has a relatively large impact on the size of the coronavirus epidemic in Uganda. We find that the critical mask adherence is 5 per 100 when 80% wear face masks. A cost-effective analysis shows that utilizing funds to provide 1 public mask to the population has a per capita compounded cost of USD 1.34. If provision of face masks is done simultaneously with supportive care, the per capita compounded cost is USD 1.965, while for the case of only treatment and no provision of face masks costs each Ugandan USD 4.0579. We conclude that since it is hard to achieve a 100% adherence to face masks, government might consider provision of face masks in conjunction with provision of care.
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    Estimating the Effect and Cost-Effectiveness of Facemasks in Reducing the Spread of the Severe Acute Respiratory Syndrome- Coronavirus 2 (SARS-CoV-2) in Uganda
    (CC-BY-ND 4.0 International license ., 2020) Nannyonga, Betty K.; Wanyenze, Rhoda K.; Kaleebu, Pontiano; Ssenkusu, John M.; Lutalo, Tom; Makumbi, Fredrick Edward; Kwizera, Arthur; Byakika, Pauline; Kirungi, Willford; Kyobe Bosa, Henry; Ssembatya, Vincent A.; Mwebesa, Henry; Atwine, Diana; Aceng, Jane Ruth; Woldermariamç, Yonas Tegegn
    Evidence that face masks provide effective protection against respiratory infections in the community is scarce. However, face masks are widely used by health workers as part of droplet precautions when caring for patients with respiratory infections. It would therefore be reasonable to suggest that consistent widespread use of face masks in the community could prevent further spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARSCoV- 2). In this study we examine public face mask wearing in Uganda where a proportion wears masks to protect against acquiring, and the other to prevent from transmitting SARSCoV- 2. The objective of this study was to determine what percentage of the population would have to wear face masks to reduce susceptibility to and infectivity of SARS-COV-2 in Uganda, keeping the basic reproduction number below unity and/or flattening the curve. We used an SEIAQRD model for the analysis
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    Ethical and Scientific Considerations on the Establishment of a Controlled Human Infection Model for Schistosomiasis in Uganda: report of a stakeholders’ meeting held in Entebbe, Uganda.
    (AAS open research, 2018) Elliott, Alison M.; Wajja, Anne; Opio, Christopher; Angumya, Francis; Adriko, Moses; Egesa, Moses; Mfutso-Bengo, Joseph; Kapulu, Melissa; Lutalo, Tom; Nazziwa, Winfred Badanga; Muwumuza, Asuman; Kaleebu, Pontiano; Kabatereine, Narcis; Tukahebwa, Edridah
    Controlled human infection (CHI) models are gaining recognition as an approach to accelerating vaccine development, for use in both non-endemic and endemic populations: they can facilitate identification of the most promising candidate vaccines for further trials and advance understanding of protective immunity. Helminths present a continuing health burden in sub-Saharan Africa. Vaccine development for these complex organisms is particularly challenging, partly because protective responses are akin to mechanisms of allergy. A CHI model for Schistosoma mansoni (CHI-S) has been developed at Leiden University Medical Centre, the Netherlands. However, responses to schistosome infections, and candidate vaccines, are likely to be different among people from endemic settings compared to schistosome-naïve Dutch volunteers. Furthermore, among volunteers from endemic regions who have acquired immune responses through prior exposure, schistosome challenge can be used to define responses associated with clinical protection, and thus to guide vaccine development. To explore the possibility of establishing the CHI-S in Uganda, a Stakeholders’ Meeting was held in Entebbe in 2017. Regulators, community members, researchers and policy-makers discussed implementation challenges and recommended preparatory steps: risk assessment; development of infrastructure and technical capacity to produce the infectious challenge material in Uganda; community engagement from Parliamentary to grass-roots level; pilot studies to establish approaches to assuring fully informed consent and true voluntariness, and strategies for selection of volunteers who can avoid natural infection during the 12-week CHI-S; the building of regulatory capacity; and the development of study protocols and a product dossier in close consultation with ethical and regulatory partners. It was recommended that, on completion, the protocol and product dossier be reviewed for approval in a joint meeting combining ethical, regulatory and environment management authorities. Most importantly, representatives of schistosomiasis-affected communities emphasised the urgent need for an effective vaccine and urged the research community not to delay in the development process.
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    Evaluation of HIV-1 Rapid Tests and Identification of alternative Testing Algorithms for Use in Uganda
    (BMC Infectious Diseases, 2018) Kaleebu, Pontiano; Kitandwe, Paul Kato; Lutalo, Tom; Kigozi, Aminah; Watera, Christine; Nanteza, Mary Bridget; Musinguzi, Joshua; Opio, Alex; Downing, Robert; Mbidde, Edward Katongole
    The World Health Organization recommends that countries conduct two phase evaluations of HIV rapid tests (RTs) in order to come up with the best algorithms. In this report, we present the first ever such evaluation in Uganda, involving both blood and oral based RTs. The role of weak positive (WP) bands on the accuracy of the individual RT and on the algorithms was also investigated.
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    Field evaluation of the performance of seven Antigen Rapid diagnostic tests for the diagnosis of SARs-CoV-2 virus infection in Uganda
    (Plos one, 2022) Bwogi, Josephine; Lutalo, Tom; Tushabe, Phionah; Bukenya, Henry; Eliku, James Peter; Ssewanyana, Isaac; Nabadda, Susan; Nsereko, Christopher; Matthew, Cotten; Robert, Downing; Lutwama, Julius; Kaleebu, Pontiano
    Objective The objective of this study was to evaluate the performance of seven antigen rapid diagnostic tests (Ag RDTs) in a clinical setting to identify those that could be recommended for use in the diagnosis of SARS-CoV-2 infection in Uganda. Methods This was a cross-sectional prospective study. Nasopharyngeal swabs were collected consecutively from COVID-19 PCR positive and COVID-19 PCR negative participants at isolation centers and points of entry, and tested with the SARS-CoV-2 Ag RDTs. Test sensitivity and specificity were generated by comparing results against qRT-PCR results (Berlin Protocol) at a cycle threshold (Ct) cut-off of ≤39. Sensitivity was also calculated at Ct cut-offs ≤29 and ≤33. Results None of the Ag RDTs had a sensitivity of ≥80% at Ct cut-off values ≤33 and ≤39. Two kits, Panbio™ COVID-19 Ag and VivaDiag™ SARS-CoV-2 Ag had a sensitivity of ≥80% at a Ct cut-off value of ≤29. Four kits: BIOCREDIT COVID -19 Ag, COVID-19 Ag Respi-Strip, MEDsan® SARS-CoV-2 Antigen Rapid Test and Panbio™ COVID-19 Ag Rapid Test had a specificity of ≥97%. Conclusions This evaluation identified one Ag RDT, Panbio™ COVID-19 Ag with a performance at high viral load (Ct value ≤29) reaching that recommended by WHO. This kit was recommended for screening of patients with COVID -19-like symptoms presenting at health facilities.
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    First Trial Of The HIV­1 Vaccine In Africa: Ugandan Experience
    (Bmj, 2002) Mugerwa, Roy D.; Kaleebu, Pontiano; Mugyenyi, Peter; ­Mbidde, Edward Katongole; Hom, David L.; Byaruhanga, Rose; Salata, Robert A.; Ellner, Jerrold J.; HIV­1 Vaccine Trial Group
    Trials of the HIV­1 vaccine have been conducted in Europe, North America, Brazil, China, and Thailand.1 The first trial of a candidate vaccine in Africa was recently completed in Uganda. It involved a ran­domised, placebo controlled trial of a vaccine in healthy volunteers at low risk of HIV infection.2 3 The vaccine, called “ALVAC­HIV,” uses a live recombinant canarypox vector to express envelope and core genes of HIV­1. Many commentators predicted that it would be dif­ficult to conduct trials of HIV vaccines in developing countries because of scientific, sociobehavioural, ethical, and logistical barriers.4–8 Before we started the trial in Uganda, we gathered data to help us overcome these potential barriers. We collected epidemiological9 and sociobehavioural10 data about people who had participated in studies that looked at preparing for trials of the HIV vaccine. These data showed the preva­lence and incidence of HIV, behaviours placing people at risk of becoming infected with HIV, and the social acceptability of a vaccine against HIV.9–11 The people received detailed education and counselling about infection with HIV and about HIV vaccines, and we recruited some for our trial.11We organised three open workshops at the HIV candidate vaccine trial workshop in Kampala in 1996 to gain consensus from scientists, policy makers, community representatives, and the media about how to undertake research into HIV vaccines. Despite these initiatives to solve problems before the trial began, we still encountered many barriers. In this article, we discuss these barriers and the strategiesthat we developed to overcome them.
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    Genotypic Variation in the pol Gene of HIV Type 1 in an Antiretroviral Treatment-Naive Population in Rural Southwestern Uganda
    (AIDS Research & Human Retroviruses, 2006) Gale, Catherine V.; Yirrell, David L.; Campbell, Eileen; Kaleebu, Pontiano
    The majority of studies of HIV-1 drug resistance have involved subtype B viruses. Here we have characterized subtype distribution and determined the levels of polymorphism at protease (PR) and reverse transcriptase (RT) drug resistance positions, in antiretroviral treatment-naive HIV-positive Ugandan patients. We have also investigated codon usage variability at these positions and assessed intersubtype recombination within the polgene. The study population consisted of 187 patients, from a cohort established by the UK Medical Research Council Programme on AIDS in Uganda in 1990. Results indicate that 28.3% of patients were infected with subtype A (n 53), 64.2% subtype D (n 120), 6.4% A/D recombinant (n 12), and 1.1% subtype C (n 2). Variation in amino acid usage at drug resistance-associated positions was minimal between the two main subtypes (A and D) in RT, but there was appreciable variation in PR. Codon usage, however, was considerably more variable between subtypes A and D in both PR and RT. Thus, while no natural high-level resistance to antiretroviral therapy was detected in this cohort, subtypes A and D may possess different genetic barriers to be overcome in order to achieve resistance. With the increasing introduction of antiretroviral therapy into Africa, such information will be vital in our understanding and evaluation of the development of drug resistance as it occurs, and how to interpret resistance data the type of which has rarely previously been seen. This analysis also significantly increases the number of Ugandan PR and RT sequences characterized to date.
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    Hepatitis B serological markers and plasma DNA concentrations: baseline results from a treatment-monitoring practices trial
    (Aids, 2017-02-03) Price, Huw; Tamale, Zachary; Chirara, Michael; Hakime, James; Kaleebu, Pontiano; Gilsona, Richard
    To examine hepatitis B (HBV) serological markers and plasma DNA concentrations in a large group of untreated HBV/HIV-coinfected individuals in two sub-Saharan settings. Baseline analysis of a randomized controlled trial. DART was a large trial of treatmentmonitoring practices in HIV-infected adults with advanced disease starting antiretroviral therapy at centres in Kampala or Entebbe, Uganda (n¼2317) and Harare, Zimbabwe (n¼999). HBV serological markers [antibody to HBV core antigen, HBV surface antigen (HBsAg), antibody to HBV surface antigen, HBV ‘e’ antigen (HBeAg), and antibody to hepatitis B ‘e’ antigen] and plasma HBV DNA viral load were measured retrospectively on stored baseline samples. Logistic regression was used to examine associations with baseline demographic and clinical factors. The rate of HBsAg positivity was significantly higher in Zimbabwe than Uganda (16.7 vs. 6.1%, adjusted odds ratio¼2.99, P<0.001) despite a similar prevalence of antibody to HBV core antigen (56.3 vs. 52.4%) in the two settings. Overall, HBsAg positivity was associated with male sex (adjusted odds ratio¼1.54, P<0.001) but not with age, WHO disease stage, or CD4þ cell count. HBeAg was detected among 37% of HBsAg-positive patients, with higher rates among those with advanced WHO stage (P¼0.02). Also in HBsAg-positive patients, HBV DNA was undetectable in 21%, detectable but below the level of quantification in 14%, and quantifiable in 65%. A total of 96% of HBeAg-positive and 70% of HBeAg-negative patients had detectable HBV DNA; 92 and 28% of patients, respectively, had HBVDNA viral load more than 2000 IU/ml. Conclusion: High rates of HBV coinfection were observed, highlighting the importance
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    High HIV-1 prevalence, risk behaviours, and willingness to participate in HIV vaccine trials in fishing communities on Lake Victoria, Uganda
    (Journal of the International AIDS Society, 2013) Kiwanuka, Noah; Ssetaala, Ali; Mpendo, Juliet; Wambuzi, Matthias; Nanvubya, Annet; Sigirenda, Simon; Nalutaaya, Annet; Kato, Paul; Nielsen, Leslie; Kaleebu, Pontiano; Nalusiba, Josephine; Sewankambo, Nelson K
    HIV epidemics in sub-Saharan Africa are generalized, but high-risk subgroups exist within these epidemics. A recent study among fisher-folk communities (FFC) in Uganda showed high HIV prevalence (28.8%) and incidence (4.9/100 person-years). However, those findings may not reflect population-wide HIV rates in FFC since the study population was selected for high-risk behaviour. Between September 2011 and March 2013, we conducted a community-based cohort study to determine the population representative HIV rates and willingness to participate (WTP) in hypothetical vaccine trials among FFC, Uganda. At baseline (September 2011January 2012), a household enumeration census was done in eight fishing communities (one lakeshore and seven islands), after which a random sample of 2200 participants aged 1849 years was selected from 5360 individuals. Interviewer-administered questionnaire data were collected on HIV risk behaviours and WTP, and venous blood was collected for HIV testing using rapid HIV tests with enzyme-linked immunosorbent assay (EIA) confirmation. Adjusted prevalence proportion ratios (adj.PPRs) of HIV prevalence were determined using log-binomial regression models. Overall baseline HIV prevalence was 26.7% and was higher in women than men (32.6% vs. 20.8%, pB0.0001). Prevalence was lower among fishermen (22.4%) than housewives (32.1%), farmers (33.1%) and bar/lodge/restaurant workers (37%). The adj.PPR of HIV was higher among women than men (adj.PPR 1.50, 95%; 1.20, 1.87) and participants aged 3039 years (adj.PPR 1.40, 95%; 1.10, 1.79) and 4049 years (adj.PPR 1.41, 95%; 1.04, 1.92) compared to those aged 1824 years. Other factors associated with HIV prevalence included low education, previous marriage, polygamous marriage, alcohol and marijuana use before sex. WTP in hypothetical vaccine trials was 89.3% and was higher in men than women (91.2% vs. 87.3%, p 0.004) and among island communities compared to lakeshore ones (90.4% vs. 85.8%, p 0.004). The HIV prevalence in the general fisher-folk population in Uganda is similar to that observed in the ‘‘high-risk’’ fisher folk. FFC have very high levels of willingness to participate in future HIV vaccine trials.
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    High Rate of HIV Resuppression After Viral Failure on First-line Antiretroviral Therapy in the Absence of Switch to Second-line Therapy
    (Clinical infectious diseases, 2014) Gupta, Ravindra K.; Goodall, Ruth L.; Kityo, Cissy; Munderi, Paula; Lyagoba, Fred; Mugarura, Lincoln; Kaleebu, Pontiano; Pillay, Deenan
    In a randomized comparison of nevirapine or abacavir with zidovudine plus lamivudine, routine viral load monitoring was not performed, yet 27% of individuals with viral failure at week 48 experienced resuppression by week 96 without switching. This supports World Health Organization recommendations that suspected viral failure should trigger adherence counseling and repeat measurement before a treatment switch is considered.
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    High Rate of HIV Resuppression After Viral Failure on First-line Antiretroviral Therapy in the Absence of Switch to Second-line Therapy
    (Clinical infectious diseases, 2013-12-18) Gupta, Ravindra K.; Ranopa, Michael; Kityo, Cissy; Lyagoba, Fred; Mugarura,Lincoln; Kaleebu, Pontiano
    In a randomized comparison of nevirapine or abacavir with zidovudine plus lamivudine, routine viral load monitoring was not performed, yet 27% of individuals with viral failure at week 48 experienced resuppression by week 96 without switching. This supports World Health Organization recommendations that suspected viral failure should trigger adherence counseling and repeat measurement before a treatment switch is considered.