Browsing by Author "Kabuye, Geoffrey"
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Item Distribution of HLA-B alleles in a Ugandan HIV-infected adult population: NORA pharmacogenetic substudy of DART(Tropical medicine & international health, 2011) Munderi, Paula; Snowden, Wendy B.; Kityo, Cissy; Kabuye, Geoffrey; Thoofer, Navdeep K.; Ssali, Francis; Gilks, Charles F.; Hughes, Arlene R.To determine the frequencies of HLA-B alleles in Ugandan patients in the NORA substudy of the DART trial and to compare HLA-B allele frequencies in those with and without clinically diagnosed hypersensitivity reaction (HSR). DNA-based HLA-B genotyping was used to determine HLA alleles in 247 participants who received abacavir, including all six participants (‘cases’) with clinically diagnosed abacavir HSR. The incidence of clinical abacavir HSR in this double-blinded study was 2.0% (6/300) in the abacavir group. As HLA-B*5701 was absent throughout the entire cohort, including the six HSR ‘cases’, an association could not be established between HLA-B*5701 and clinically diagnosed abacavir HSR. No other HLA-B*57 alleles were present among the six ‘cases’. HLA-B*5703 was the most frequent HLA-B*57 allele among the abacavir-tolerant participants. The rate of clinical HSR was low, which may reflect the expected 2–3% clinical false-positive rate seen in previous double-blind randomized studies. The presumption that these cases may be false-positive abacavir HSR is supported by the fact that no HLA-B*5701 alleles were found in the abacavir group. Implementation of prospective HLA-B*5701 screening must be based on benefit/risk considerations within local practice. Clinical risk management remains paramount.Item Distribution of HLA-B alleles in a Ugandan HIV-infected adult population: NORA pharmacogenetic substudy of DART(Tropical medicine & international health, 2011-11-23) Munderi, Paula; Kityo, Cissy; Kabuye, Geoffrey; Hughes, Arlene R.To determine the frequencies of HLA-B alleles in Ugandan patients in the NORA substudy of the DART trial and to compare HLA-B allele frequencies in those with and without clinically diagnosed hypersensitivity reaction (HSR). DNA-based HLA-B genotyping was used to determine HLA alleles in 247 participants who received abacavir, including all six participants (‘cases’) with clinically diagnosed abacavir HSR. The incidence of clinical abacavir HSR in this double-blinded study was 2.0% (6/300) in the abacavir group. As HLA-B*5701 was absent throughout the entire cohort, including the six HSR ‘cases’, an association could not be established between HLA-B*5701 and clinically diagnosed abacavir HSR. No other HLA-B*57 alleles were present among the six ‘cases’. HLA-B*5703 was the most frequent HLA-B*57 allele among the abacavir-tolerant participants. The rate of clinical HSR was low, which may reflect the expected 2–3% clinical false-positive rate seen in previous double-blind randomized studies. The presumption that these cases may be false-positive abacavir HSR is supported by the fact that no HLA-B*5701 alleles were found in the abacavir group. Implementation of prospective HLA-B*5701 screening must be based on benefit/risk considerations within local practice. Clinical risk management remains paramount.Item Effect of debranching on the rheological properties of Ca2þ epectin gels(Food Hydrocolloids, 2012-01-18) Ngouémazong, Doungla E.; Kabuye, Geoffrey; Cardinaels, Ruth; Hendrickx, MarcWater-soluble pectin (WSP) extract was subjected to controlled carrot pectin methylesterase treatment, thereby producing de-esterified pectin (DEP). Both WSP and DEP were incubated with a mixture of endo-arabinanase and α-L-arabinofuranosidase to yield partially debranched pectins (WSPDBr and DEPDBr respectively). Pectin samples were characterised in terms of degree of methylesterification (DM), neutral sugar content, and degree of branching (DBr). The characterised pectins were used for the preparation of pectin gels with high and low calcium ion (Ca2+) concentrations. The rheological characteristics of the produced gels were evaluated by means of small-amplitude oscillatory tests. These characteristics include network development of the gel, gel strength (G′), gel elastic character and gel type. Partial debranching of pectin resulted in a reduction of the arabinose content (by approximately 50%) and caused a slight decrease in polymer DBr. Gels produced from semi-dilute solutions of partially debranched pectins showed network development profiles similar to those prepared from semi-dilute solutions of the corresponding non-debranched polymers. Yet, the former gels showed lower G′ values, poor gel elastic character and a “weaker” nature as compared to the latter. Next to Ca2+ cross-links, the presence of long arabinose-containing side chains is suggested to play an important role in the rheological characteristics of Ca2+–pectin gels.Item Effectiveness of Voluntary Medical Male Circumcision for Human Immunodeficiency Virus Prevention in Rakai, Uganda(Clinical Infectious Diseases, 2021) Loevinsohn, Gideon; Kigozi, Godfrey; Kagaayi, Joseph; Wawer, Maria J.; Nalugoda, Fred; Chang, Larry W.; Quinn, Thomas C.; Serwadda, David; Reynolds, Steven J.; Nelson, Lisa; Mills, Lisa; Alamo, Stella; Nakigozi, Gertrude; Kabuye, Geoffrey; Ssekubugu, Robert; Tobian, Aaron A. R.; Gray, Ronald H.; Grabowski, M. KathrynThe efficacy of voluntary male medical circumcision (VMMC) for human immunodeficiency virus (HIV) prevention in men was demonstrated in 3 randomized trials. This led to the adoption of VMMC as an integral component of the United States President’s Emergency Plan for AIDS Relief (PEPFAR) combination HIV prevention program in sub-Saharan Africa. However, evidence on the individual-level effectiveness of VMMC programs in real-world, programmatic settings is limited. A cohort of initially uncircumcised, non-Muslim, HIV-uninfected men in the Rakai Community Cohort Study in Uganda was followed between 2009 and 2016 during VMMC scale-up. Self-reported VMMC status was collected and HIV tests performed at surveys conducted every 18 months. Multivariable Poisson regression was used to estimate the incidence rate ratio (IRR) of HIV acquisition in newly circumcised vs uncircumcised men.Item Effects of COVID-19 Pandemic on Voluntary Medical Male Circumcision Services for HIV Prevention, Sub-Saharan Africa, 2020(Emerging Infectious Diseases, 2022-12-28) Peck, Megan E.; Ong, Katherine S.; Kiggundu, Valerian; Bamwesigye, Jackson; Semakula, Muhammed; Kabuye, Geoffrey; Kyobutungi, Sheila; Makumbi, Fredrick E.; Toledo, CarlosBeginning in March 2020, to reduce COVID-19 transmission, the US President’s Emergency Plan for AIDS Relief supporting voluntary medical male circumcision (VMMC) services was delayed in 15 sub-Saharan African countries. We reviewed performance indicators to compare the number of VMMCs performed in 2020 with those performed in previous years. In all countries, the annual number of VMMCs performed decreased 32.5% (from 3,898,960 in 2019 to 2,631,951 in 2020). That reduction is largely attributed to national and local COVID-19 mitigation measures instituted by ministries of health. Overall, 66.7% of the VMMC global annual target was met in 2020, compared with 102.0% in 2019. Countries were not uniformly affected; South Africa achieved only 30.7% of its annual target in 2020, but Rwanda achieved 123.0%. Continued disruption to the VMMC program may lead to reduced circumcision coverage and potentially increased HIV-susceptible populations. Strategies for modifying VMMC services provide lessons for adapting healthcare systems during a global pandemic.Item HIV Incidence by Male Circumcision Status From the Population-Based HIV Impact Assessment Surveys—Eight Sub-Saharan African Countries, 2015–2017(JAIDS Journal of Acquired Immune Deficiency Syndromes, 2021) Hines, Jonas Z.; Sachathep, Karampreet; Pals, Sherri; Davis, Stephanie M.; Toledo, Carlos; Bronson, Megan; Parekh, Bharat; Carrasco, Maria; Xaba, Sinokuthemba; Mandisarisa, John; Kamobyi, Royd; Chituwo, Omega; Kirungi, Wilford L.; Alamo, Stella; Kabuye, Geoffrey; Awor, Anna Colletar; Mmbando, Susan; Simbeye, Daimon; Aupokolo, Mekondjo A.; Zemburuka, Brigitte; Nyirenda, Rose; Msungama, Wezi; Tarumbiswa, Tapiwa; Manda, Robert; Biribonwoha, Harriet Nuwagaba; Kiggundu, Valerian; Thomas, Anne G.; Voetsch, Andrew C.; Williams, Dan B.Conducting HIV surveys in resource-limited settings is challenging because of logistics, limited availability of trained personnel, and complexity of testing. We described the procedures and systems deemed critical to ensure high-quality laboratory data in the population-based HIV impact assessments and large-scale household surveys.Laboratory professionals were engaged in every stage of the surveys, including protocol development, site assessments, procurement, training, quality assurance, monitoring, analysis, and reporting writing. A tiered network of household, satellite laboratories, and central laboratories, accompanied with trainings, optimized process for blood specimen collection, storage, transport, and real-time monitoring of specimen quality, and test results at each level proved critical in maintaining specimen integrity and high-quality testing. A plausibility review of aggregate merged data was conducted to confirm associations between key variables as a final quality check for quality of laboratory results.Overall, we conducted a hands-on training for 3355 survey staff across 13 surveys, with 160–387 personnel trained per survey on biomarker processes. Extensive training and monitoring demonstrated that overall, 99% of specimens had adequate volume and 99.8% had no hemolysis, indicating high quality. We implemented quality control and proficiency testing for testing, resolved discrepancies, verified >300 Pima CD4 instruments, and monitored user errors. Aggregate data review for plausibility further confirmed the high quality of testing.Ongoing engagement of laboratory personnel to oversee processes at all levels of the surveys is critical for successful national surveys. High-quality population-based HIV impact assessments laboratory data ensured reliable results and demonstrated the impact of HIV programs in 13 countries.Item HIV, syphilis, and hepatitis B virus infection and male circumcision in five Sub-Saharan African countries: Findings from the Population-based HIV Impact Assessment surveys, 2015–2019(PLOS Global Public Health, 2023-09-18) Peck, Megan E.; Kankindi, Ida; Biraro, Samuel; Kabuye, Geoffrey; Kirungi, WilfordVoluntary medical male circumcision (VMMC) has primarily been promoted for HIV prevention. Evidence also supports that male circumcision offers protection against other sexually transmitted infections. This analysis assessed the effect of circumcision on syphilis, hepatitis B virus (HBV) infection and HIV. Data from the 2015 to 2019 Population-based HIV Impact Assessments (PHIAs) surveys from Rwanda, Tanzania, Uganda, Zambia, and Zimbabwe were used for the analysis. The PHIA surveys are cross-sectional, nationally representative household surveys that include biomarking testing for HIV, syphilis and HBV infection. This is a secondary data analysis using publicly available PHIA data. Univariate and multivariable logistic regression models were created using pooled PHIA data across the five countries to assess the effect of male circumcision on HIV, active and ever syphilis, and HBV infection among sexually active males aged 15–59 years. Circumcised men had lower odds of syphilis infection, ever or active infection, and HIV, compared to uncircumcised men, after adjusting for covariates (active syphilis infection = 0.67 adjusted odds ratio (aOR), 95% confidence interval (CI), 0.52–0.87, ever having had a syphilis infection = 0.85 aOR, 95% CI, 0.73–0.98, and HIV = 0.53 aOR, 95% CI, 0.47–0.61). No difference between circumcised and uncircumcised men was identified for HBV infection (P = 0.75). Circumcised men have a reduced likelihood for syphilis and HIV compared to uncircumcised men. However, we found no statistically significant difference between circumcised and uncircumcised men for HBV infection.Item Preventing HIV among Adolescent Boys and Young Men through Pepfar-Supported Voluntary Medical Male Circumcision In 15 Sub-Saharan African Countries, 2018–2021(AIDS Education and Prevention, 2023-07-14) Peck, Megan E.; Wandira, Ronald; Kazaura, Kokuhumbya J.; Kabuye, Geoffrey; Toledo, CarlosVoluntary medical male circumcision (VMMC) is an HIV prevention intervention that has predominantly targeted adolescent and young men, aged 10–24 years. In 2020, the age eligibility for VMMC shifted from 10 to 15 years of age. This report describes the VMMC client age distribution from 2018 to 2021, at the site, national, and regional levels, among 15 countries in southern and eastern Africa. Overall, in 2018 and 2019, the highest proportion of VMMCs were performed among 10–14-year-olds (45.6% and 41.2%, respectively). In 2020 and 2021, the 15–19-year age group accounted for the highest proportion (37.2% and 50.4%, respectively) of VMMCs performed across all age groups. Similarly, in 2021 at the site level, 68.1% of VMMC sites conducted the majority of circumcisions among men aged 15–24 years. This analysis highlights that adolescent boys and young men are the primary recipients of VMMC receiving an important lifetime reduction in HIV risk.Item A Randomized, Controlled, Trial of Short Cycle Intermittent Compared to Continuous Antiretroviral Therapy for the Treatment of HIV Infection in Uganda(PLoS One, 2010) Reynolds, Steven J.; Kityo, Cissy; Kabuye, Geoffrey; Atwiine, Diana; Mbamanya, Frank; Ssali, Francis; Davey, Richard T.; Mugyenyi, Peter; Fauci, Anthony S.; Dybul, Mark R.Short cycle treatment interruption could reduce toxicity and drug costs and contribute to further expansion of antiretroviral therapy (ART) programs. A 72 week, non-inferiority trial enrolled one hundred forty six HIV positive persons receiving ART (CD4+ cell count $125 cells/mm3 and HIV RNA plasma levels ,50 copies/ml) in one of three arms: continuous, 7 days on/7 days off and 5 days on/2 days off treatment. Primary endpoint was ART treatment failure determined by plasma HIV RNA level, CD4+ cell count decrease, death attributed to study participation, or opportunistic infection. Following enrollment of 32 participants, the 7 days on/7 days off arm was closed because of a failure rate of 31%. Six of 52 (11.5%) participants in the 5 days on/2 days off arm failed. Five had virologic failure and one participant had immunologic failure. Eleven of 51 (21.6%) participants in the continuous treatment arm failed. Nine had virologic failure with 1 death (lactic acidosis) and 1 clinical failure (extra-pulmonary TB). The upper 97.5% confidence boundary for the difference between the percent of non-failures in the 5 days on/2 days off arm (88.5% non-failure) compared to continuous treatment (78.4% non failure) was 4.8% which is well within the preset non-inferiority margin of 15%. No significant difference was found in time to failure in the 2 study arms (p = 0.39). Short cycle 5 days on/2 days off intermittent ART was at least as effective as continuous therapyItem Scale-Up of Voluntary Medical Male Circumcision Services for HIV Prevention — 12 Countries in Southern and Eastern Africa, 2013–2016(Morbidity and Mortality Weekly Report, 2017) Hines, Jonas Z.; Malaba, Kananga; Zegeye, Tiruneh; June, Elijah Odoyo; Nyirenda, Rose Kolola; Mutandi, Gram; Yoboka, Emmanuel; Maringa, Hilda; Simbeye, Daimon; Kazaura, Kokuhumbya; Lubwama, Joseph; Kabuye, Geoffrey; Mumba, Maybin; Toledo, CarlosCountries in Southern and Eastern Africa have the highest prevalence of human immunodeficiency virus (HIV) infection in the world; in 2015, 52% (approximately 19 million) of all persons living with HIV infection resided in these two regions.* Voluntary medical male circumcision (VMMC) reduces the risk for heterosexually acquired HIV infection among males by approximately 60% (1). As such, it is an essential component of the Joint United Nations Programme on HIV/AIDS (UNAIDS) strategy for ending acquired immunodeficiency syndrome (AIDS) by 2030 (2). Substantial progress toward achieving VMMC targets has been made in the 10 years since the World Health Organization (WHO) and UNAIDS recommended scale-up of VMMC for HIV prevention in 14 Southern and Eastern African countries with generalized HIV epidemics and low male circumcision prevalence (3).† This has been enabled in part by nearly $2 billion in cumulative funding through the President’s Emergency Plan for AIDS Relief (PEPFAR), administered through multiple U.S. governmental agencies, including CDC, which has supported nearly half of all PEPFAR-supported VMMCs to date. Approximately 14.5 million VMMCs were performed globally during 2008–2016, which represented 70% of the original target of 20.8 million VMMCs in males aged 15–49 years through 2016 (4). Despite falling short of the target, these VMMCs are projected to avert 500,000 HIV infections by the end of 2030 (4). However, UNAIDS has estimated an additional 27 million VMMCs need to be performed by 2021 to meet the Fast Track targets (2). This report updates a previous report covering the period 2010–2012, when VMMC implementing partners supported by CDC performed approximately 1 million VMMCs in nine countries (5). During 2013–2016, these implementing partners performed nearly 5 million VMMCs in 12 countries. Meeting the global target will require redoubling current efforts and introducing novel strategies that increase demand among subgroups of males who have historically been reluctant to undergo VMMC.