Browsing by Author "Kasozi, Charles"

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    Beyond T Staging in the “Treat All” Era: Severity and Heterogeneity of Kaposi’s Sarcoma in East Africa
    (Wolters Kluwer, 2021) Freeman, Esther E.; Semeere, Aggrey; McMahon, Devon E.; Byakwaga, Helen; Laker-Oketta, Miriam; Regan, Susan; Wenger, Megan; Kasozi, Charles; Semakadde, Matthew; Bwana, Mwebesa; Kanyesigye, Michael; Kadama-Makanga, Philippa; Rotich, Elyne; Kisuya, Job; Wools-Kaloustian, Kara; Bassett, Ingrid V.; Busakhala, Naftali; Martin, Jeffrey; Medicine, School of Medicine
    Background: Although many patients with Kaposi sarcoma (KS) in sub-Saharan Africa are diagnosed with AIDS Clinical Trials Group (ACTG) T1 disease, T1 staging insufficiently captures clinical heterogeneity of advanced KS. Using a representative community-based sample, we detailed disease severity at diagnosis to inform KS staging and treatment in sub-Saharan Africa. Methods: We performed rapid case ascertainment on people living with HIV, aged 18 years or older, newly diagnosed with KS from 2016 to 2019 at 3 clinic sites in Kenya and Uganda to ascertain disease stage as close as possible to diagnosis. We reported KS severity using ACTG and WHO staging criteria and detailed measurements that are not captured in the current staging systems. Results: We performed rapid case ascertainment within 1 month for 241 adults newly diagnosed with KS out of 389 adult patients with suspected KS. The study was 68% men with median age 35 years and median CD4 count 239. Most of the patients had advanced disease, with 82% qualifying as ACTG T1 and 64% as WHO severe/symptomatic KS. The most common ACTG T1 qualifiers were edema (79%), tumor-associated ulceration (24%), extensive oral KS (9%), pulmonary KS (7%), and gastrointestinal KS (4%). There was marked heterogeneity within T1 KS, with 25% of patients having 2 T1 qualifying symptoms and 3% having 3 or more. Conclusion: Most of the patients newly diagnosed with KS had advanced stage disease, even in the current antiretroviral therapy "treat-all" era. We observed great clinical heterogeneity among advanced stage patients, leading to questions about whether all patients with advanced KS require the same treatment strategy.
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    Feasibility of Rapid Case Ascertainment for Cancer in East Africa: An Investigation of Community-Representative Kaposi Sarcoma in the Era of Antiretroviral Therapy
    (Elsevier, 2021) Semeere, Aggrey; Byakwaga, Helen; Laker-Oketta, Miriam; Freeman, Esther; Busakhala, Naftali; Wenger, Megan; Kasozi, Charles; Ssemakadde, Matthew; Bwana, Mwebesa; Kanyesigye, Michael; Kadama-Makanga, Philippa; Rotich, Elyne; Kisuya, Job; Sang, Edwin; Maurer, Toby; Wools-Kaloustian, Kara; Kambugu, Andrew; Martin, Jeffrey; Medicine, School of Medicine
    Background: Rapid case ascertainment (RCA) refers to the expeditious and detailed examination of patients with a potentially rapidly fatal disease shortly after diagnosis. RCA is frequently performed in resource-rich settings to facilitate cancer research. Despite its utility, RCA is rarely implemented in resource-limited settings and has not been performed for malignancies. One cancer and context that would benefit from RCA in a resource-limited setting is HIV-related Kaposi sarcoma (KS) in sub-Saharan Africa. Methods: To determine the feasibility of RCA for KS, we searched for all potential newly diagnosed KS among HIV-infected adults attending three community-based facilities in Uganda and Kenya. Searching involved querying of electronic medical records, pathology record review, and notification by clinicians. Upon identification, a team verified eligibility and attempted to locate patients to perform RCA, which included epidemiologic, clinical and laboratory measurements. Results: We identified 593 patients with suspected new KS. Of the 593, 171 were ineligible, mainly because biopsy failed to confirm KS (65%) or KS was not new (30%). Among the 422 remaining, RCA was performed within 1 month for 56% of patients and within 3 months for 65% (95% confidence interval: 59 to 70%). Reasons for not performing RCA included intervening death (47%), inability to contact (44%), refusal/unsuitable to consent (8.3%), and patient re-location (0.7%). Conclusions: We found that RCA - an important tool for cancer research in resource-rich settings - is feasible for the investigation of community-representative KS in East Africa. Feasibility of RCA for KS suggests feasibility for other cancers in Africa.
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    Global HIV mortality trends among children on antiretroviral treatment corrected for under‐reported deaths: an updated analysis of the International epidemiology Databases to Evaluate AIDS collaboration
    (Wiley, 2021-09) Kassanjee, Reshma; Johnson, Leigh F.; Zaniewski, Elizabeth; Ballif, Marie; Christ, Benedikt; Yiannoutsos, Constantin T.; Nyakato, Patience; Desmonde, Sophie; Edmonds, Andrew; Sudjaritruk, Tavitiya; Pinto, Jorge; Vreeman, Rachel; Dahourou, Désiré Lucien; Twizere, Christelle; Kariminia, Azar; Carlucci, James G.; Kasozi, Charles; Davies, Mary-Ann; Biostatistics, School of Public Health
    Introduction: The Joint United Nations Programme on HIV/AIDS (UNAIDS) projections of paediatric HIV prevalence and deaths rely on the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium for mortality estimates among children living with HIV (CHIV) receiving antiretroviral therapy (ART). Previous estimates, based on data through 2014, may no longer be accurate due to expanded paediatric HIV care and treatment eligibility, and the possibility of unreported deaths in CHIV considered lost to follow-up (LTFU). We therefore estimated all-cause mortality and its trends in CHIV (<15 years old) on ART using extended and new IeDEA data. Methods: We analysed (i) IeDEA observational data from CHIV in routine care globally, and (ii) novel data from an IeDEA tracing study that determined outcomes in a sample of CHIV after being LTFU in southern Africa. We included 45,711 CHIV on ART during 2004 to 2017 at 72 programmes in Africa, Asia-Pacific and Latin America. We used mixed effects Poisson regression to estimate mortality by age, sex, CD4 at ART start, time on ART, region and calendar year. For Africa, in an adjusted analysis that accounts for unreported deaths among those LTFU, we first modified the routine data by simulating mortality outcomes within six months after LTFU, based on a Gompertz survival model fitted to the tracing data (n = 221). Results: Observed mortality rates were 1.8 (95% CI: 1.7 to 1.9) and 9.4 (6.3 to 13.4) deaths per 100 person-years in the routine and tracing data, respectively. We found strong evidence of higher mortality at shorter ART durations, lower CD4 values, and in infancy. Averaging over covariate patterns, the adjusted mortality rate was 54% higher than the unadjusted rate. In unadjusted analyses, mortality reduced by an average 60% and 73% from 2005 to 2017, within and outside of Africa, respectively. In the adjusted analysis for Africa, this temporal reduction was 42%. Conclusions: Mortality rates among CHIV have decreased substantially over time. However, when accounting for worse outcomes among those LTFU, mortality estimates increased and temporal improvements were slightly reduced, suggesting caution in interpreting analyses based only on programme data. The improved and updated IeDEA estimates on mortality among CHIV on ART support UNAIDS efforts to accurately model global HIV statistics.
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    Survival Following Diagnosis of HIV-Associated Kaposi Sarcoma Among Adults in East Africa in the "Treat-All" Era
    (medRxiv, 2024-08-28) Byakwaga, Helen; Semeere, Aggrey; Laker-Oketta, Miriam; Busakhala, Naftali; Freeman, Esther; Rotich, Elyne; Wenger, Megan; Kadama-Makanga, Philippa; Kisuya, Job; Semakadde, Matthew; Mwine, Bronia; Kasozi, Charles; Mwebesa, Bwana; Maurer, Toby; Glidden, David V.; Wools-Kaloustian, Kara; Kambugu, Andrew; Martin, Jeffrey; Dermatology, School of Medicine
    Background: Despite widespread access to antiretroviral therapy (ART) in the "Treat All" era, HIV-associated Kaposi sarcoma (KS) remains among the most common malignancies in sub-Saharan Africa. Survival after KS diagnosis has historically been poor in Africa, but knowledge whether survival has changed at the population level in the contemporary era has been limited by lack of community-representative surveillance and monitoring systems. Methods: We identified all adult persons living with HIV (PLWH) with a new diagnosis of KS made between 2016 and 2019 during outpatient or inpatient care at prototypical primary care-providing medical facilities in Kenya and Uganda using rapid case ascertainment. Participants were subsequently followed for vital status, including community tracking for those who became lost to follow-up. Findings: Among 411 participants with newly diagnosed KS, 71% were men, median age was 34 (IQR: 30 to 41) years, and 91% had ACTG T1 tumor extent. Over a median follow-up of 7.8 (IQR: 2.4 to 17.9) months, cumulative incidence of death (95% CI) at months 6, 12 and 18 were 34% (30% to 39%), 41% (36% to 46%) and 45% (40% to 51%), respectively. Having the highest number of anatomic sites (11 to 16) harboring KS lesions (hazard ratio 2.2 (95% CI: 1.3-3.8) compared to 1 to 3 sites) and presence of oral KS lesions (hazard ratio 2.2 (95% CI: 1.4-3.3)) were independently associated with higher mortality. Lower hemoglobin and CD4 count as well as higher plasma HIV RNA were also associated with higher mortality. Interpretation: Among PLWH with newly diagnosed KS in East Africa in the "Treat All" era, survival was poor and related to mucocutaneous extent of KS. The findings emphasize the need for better control of KS in Africa, including novel approaches for earlier detection, better linkage to oncologic care, and more potent therapy.
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    Viral Load Status Before Switching to Dolutegravir-Containing Antiretroviral Therapy and Associations With Human Immunodeficiency Virus Treatment Outcomes in Sub-Saharan Africa
    (Oxford University Press, 2022) Romo, Matthew L.; Edwards, Jessie K.; Semeere, Aggrey S.; Musick, Beverly S.; Urassa, Mark; Odhiambo, Francesca; Diero, Lameck; Kasozi, Charles; Murenzi, Gad; Lelo, Patricia; Wyka, Katarzyna; Kelvin, Elizabeth A.; Sohn, Annette H.; Wools-Kaloustian, Kara K.; Nash, Denis; International epidemiology Databases to Evaluate AIDS (IeDEA); Biostatistics, School of Public Health
    Background: Dolutegravir is being rolled out globally as part of preferred antiretroviral therapy (ART) regimens, including among treatment-experienced patients. The role of viral load (VL) testing before switching patients already on ART to a dolutegravir-containing regimen is less clear in real-world settings. Methods: We included patients from the International epidemiology Databases to Evaluate AIDS consortium who switched from a nevirapine- or efavirenz-containing regimen to one with dolutegravir. We used multivariable cause-specific hazards regression to estimate the association of the most recent VL test in the 12 months before switching with subsequent outcomes. Results: We included 36 393 patients at 37 sites in 5 countries (Democratic Republic of the Congo, Kenya, Rwanda, Tanzania, Uganda) who switched to dolutegravir from July 2017 through February 2020, with a median follow-up of approximately 11 months. Compared with those who switched with a VL <200 copies/mL, patients without a recent VL test or with a preswitch VL ≥1000 copies/mL had significantly increased hazards of an incident VL ≥1000 copies/mL (adjusted hazard ratio [aHR], 2.89; 95% confidence interval [CI], 1.99-4.19 and aHR, 6.60; 95% CI, 4.36-9.99, respectively) and pulmonary tuberculosis or a World Health Organization clinical stage 4 event (aHR, 4.78; 95% CI, 2.77-8.24 and aHR, 13.97; 95% CI, 6.62-29.50, respectively). Conclusions: A VL test before switching to dolutegravir may help identify patients who need additional clinical monitoring and/or adherence support. Further surveillance of patients who switched to dolutegravir with an unknown or unsuppressed VL is needed.