Browsing by Author "Meya, David"
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Item Development and Evaluation of a Clinical Algorithm to Monitor Patients on Antiretrovirals in Resource-Limited Settings using Adherence, Clinical and CD4 Cell Count Criteria(Journal of the International AIDS Society, 2009) Meya, David; Spacek, Lisa A.; Tibenderana, Hilda; John, Laurence; Namugga, Irene; Magero, Stephen; Dewar, Robin; Quinn, Thomas C.; Colebunders, Robert; Kambugu, Andrew; Reynol, Steven J.Routine viral load monitoring of patients on antiretroviral therapy (ART) is not affordable in most resource-limited settings.A cross-sectional study of 496 Ugandans established on ART was performed at the Infectious Diseases Institute, Kampala, Uganda. Adherence, clinical and laboratory parameters were assessed for their relationship with viral failure by multivariate logistic regression. A clinical algorithm using targeted viral load testing was constructed to identify patients for second-line ART. This algorithm was compared with the World Health Organization (WHO) guidelines, which use clinical and immunological criteria to identify failure in the absence of viral load testing.Forty-nine (10%) had a viral load of >400 copies/mL and 39 (8%) had a viral load of >1000 copies/mL. An algorithm combining adherence failure (interruption >2 days) and CD4 failure (30% fall from peak) had a sensitivity of 67% for a viral load of >1000 copies/mL, a specificity of 82%, and identified 22% of patients for viral load testing. Sensitivity of the WHO-based algorithm was 31%, specificity was 87%, and would result in 14% of those with viral suppression (<400 copies/mL) being switched inappropriately to second-line ART.Algorithms using adherence, clinical and CD4 criteria may better allocate viral load testing, reduce the number of patients continued on failing ART, and limit the development of resistance.Item Evaluation of a Novel Point-of-Care Lateral Flow Assay To Detect Cryptococcal Antigen in Plasma and CSF(Opportunistic Infections, 2012) Rolfes, Melissa; Butler, Elissa; Nabeta, Henry; Kwizera, Richard; Meya, David; Boulware, DavidCurrent diagnostics for Cryptococcal meningitis (CM) rely on India ink, CSF culture, or cryptococcal antigen (CRAG) latex agglutination test. India ink is relatively insensitive. Culture and CRAG require lab infrastructure. Recently, a novel point-of-care lateral flow assay (LFA) has been FDA-approved for diagnosis of C. neoformans in serum samples. The aim of this study was to evaluate the LFA performance in plasma and CSF samples. ART-naïve subjects with and without cryptococcosis were enrolled in two prospective cohorts in Kampala, Uganda. Initial CM diagnosis was by CRAG, India ink, and quantitative CSF culture. Plasma and CSF were frozen at - 80C. Quantitative CRAG titers and LFA testing with titers were conducted on stored CSF, plasma, and serum. Plasma samples were tested in 112 subjects (n=61 with CM, n=51 with no clinical OI). CSF was tested in 161 subjects with suspected meningitis (105 with CM) from 2006-2009 and on 102 (58 with CM) in 2011. LFA results were compared for concordance with CRAG latex agglutination, India ink, and CSF culture.The LFA was highly sensitive and specific with CSF and plasma samples compared to both culture and CRAG. CRAG and LFA assays had high Kappa concordance in plasma and CSF samples, 0.93 and 0.91, respectively. LFA titers were 2.5 – 10-fold higher than CRAG titers in CSF and in plasma, respectively; however high correlation existed between the two assays (Spearman’s ρ=0.90 for plasma and 0.93 for CSF; p<0.001 for each). Culture and India ink had much lower concordance (Kappa 0.69 and 0.72, respectively) with LFA results (due to better LFA sensitivity), and titers were less correlated with quantitative culture results (ρ=0.71, p<0.001). Similar low concordance with culture and India ink were also seen with CRAG titers; suggesting the LFA results were not false-positives but more sensitive in detecting cryptococcal infection. The LFA assay has excellent concordance with CRAG latex agglutination and titers in both plasma and CSF samples and is more sensitive than standard India ink and CSF culture. Because of the wide availability of plasma samples for other clinical assessments (e.g. CD4 testing), the excellent agreement with the established CRAG assay, and the ease of use, the cryptococcal LFA holds great promise for rapid diagnosis of CM as well as the potential for cryptococcal screening prior to ART initiation, particularly in resource-limited areas.Item The impact of early monitored management on survival in hospitalized adult Ugandan patients with severe sepsis: a prospective intervention study(Critical care medicine, 2012) Jacob, Shevin T; Banura, Patrick; Baeten, Jared M.; Moore, Christopher C.; Meya, David; Nakiyingi, Lydia; Burke, Rebecca; Horton, Cheryl Lynn; Iga, Boaz; Mayanja-Kizza, Harriet; for the Promoting Resource-Limited Interventions for Sepsis Management in Uganda (PRISM-U) Study Group The impact of early monitored management on survival in hospitalized adult Ugandan patients with severe sepsis: a prospective intervention studyIn sub-Saharan Africa, sepsis is an important cause of mortality but optimal sepsis management including fluid resuscitation, early antibiotic administration and patient monitoring is limited by a lack of supplies and skilled health workers.To evaluate whether early, monitored sepsis management provided by a study medical officer can improve survival among patients with severe sepsis admitted to two public hospitals in Uganda.A prospective before and after study of an intervention cohort (n=426) with severe sepsis receiving early, monitored sepsis management compared to an observation cohort (n=245) of similarly ill patients with severe sepsis receiving standard management after admission to the medical wards of two Ugandan hospitals.Early sepsis management provided by a dedicated study medical officer comprised of fluid resuscitation, early antibiotics and regular monitoring in the first 6 hours of hospitalization.Kaplan-Meier survival and unadjusted and adjusted Cox proportional hazards analysis were used to compare the effect of early, monitored sepsis management on 30-day mortality between the intervention cohort (enrolled May 2008 to May 2009) and observation cohort (enrolled July 2006 to November 2006).The majority (86%) of patients in both cohorts were HIV-infected. Median fluid volume provided in the first 6 hours of hospitalization was higher in intervention than observation cohort patients (3000 vs. 500 mL, p<0.001) and a greater proportion of intervention cohort patients received antibacterial therapy in less than one hour (67% vs 30.4%, p<0.001). Mortality at 30 days was significantly lower in the intervention cohort compared to the observation cohort (33.0% vs 45.7%, log-rank p=0.005). After adjustment for potential confounders, the hazard of 30-day mortality was 26% less in the intervention cohort compared to the observation cohort (adjusted HR=0.74, 95% CI=0.55–0.98). Mortality among the 13% of intervention patients who developed signs of respiratory distress was associated with baseline illness severity rather than fluid volume administered.Early, monitored management of severely septic patients in Uganda improves survival and is feasible and safe even in a busy public referral hospital.Item Poor long-term outcomes despite improved hospital survival for patients with cryptococcal meningitis in rural, Northern Uganda(Public Library of Science, 2024-05) Okwir, Mark; Link, Abigail; Opio, Bosco; Okello, Fred; Nakato, Ritah; Nabongo, Betty; Alal, Jimmy; Rhein, Joshua; Meya, David; Liu, Yu; Bohjanen, Paul RCryptococcal meningitis (CM) remains a major cause of death among people living with HIV in rural sub-Saharan Africa. We previously reported that a CM diagnosis and treatment program (CM-DTP) improved hospital survival for CM patients in rural, northern Uganda. This study aimed to evaluate the impact on long-term survival. We conducted a retrospective study at Lira Regional Referral Hospital in Uganda evaluating long-term survival ([greater than or equal to]1 year) of CM patients diagnosed after CM-DTP initiation (February 2017-September 2021). We compared with a baseline historical group of CM patients before CM-DTP implementation (January 2015-February 2017). Using Cox proportional hazards models, we assessed time-to-death in these groups, adjusting for confounders. We identified 318 CM patients, 105 in the Historical Group, and 213 in the CM-DTP Group. The Historical Group had a higher 30-day mortality of 78.5% compared to 42.2% in the CM-DTP Group. The overall survival rate for the CM-DTP group at three years was 25.6%. Attendance at follow-up visits (HR:0.13, 95% CI: [0.03-0.53], p <0.001), ART adherence (HR:0.27, 95% CI: [0.10-0.71], p = 0.008), and fluconazole adherence: (HR:0.03, 95% CI: [0.01-0.13], p 50kg (HR:0.54, 95% CI: [0.35-0.84], p = 0.006), and performance of therapeutic lumbar punctures (HR:0.42, 95% CI: [0.24-0.71], p = 0.001), were associated with lower risk of death. Altered mentation was associated with increased death risk (HR: 1.63, 95% CI: 1.10-2.42, p = 0.016). Long-term survival of CM patients improved after the initiation of the CM-DTP. Despite this improved survival, long-term outcomes remained sub-optimal, suggesting that further work is needed to enhance long-term survival.Item Safety and efficacy of hydroxychloroquine for treatment of non‑severe COVID‑19 among adults in Uganda: a randomized open label phase II clinical trial(BMC Infectious Diseases, 2021) Byakika‑Kibwika, Pauline; Sekaggya‑Wiltshire, Christine; Semakula, Jerome Roy; Nakibuuka, Jane; Musaazi, Joseph; Kayima, James; Sendagire, Cornelius; Meya, David; Kirenga, Bruce; Nanzigu, Sarah; Kwizera, Arthur; Nakwagala, Fred; Kisuule, Ivan; Wayengera, Misaki; Mwebesa, Henry G.; Kamya, Moses R.; Bazeyo, WilliamSeveral repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness. Design: We conducted a randomized open label Phase II clinical trial from October–December 2020. Methods: Patients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load (CT values) from RT-PCR testing of samples collected using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6.Item Virologic suppression and associated factors in HIV infected Ugandan female sex workers: a cross-sectional study(African Health Sciences, 2021) Owachi, Darius; Anguzu, Godwin; Kigozi, Joanita; Cox, Janneke; Castelnuovo, Barbara; Semitala, Fred; Meya, DavidKey populations have disproportionately higher HIV prevalence rates than the general population. To determine the level of virologic suppression and associated factors in female Commercial Sex Workers (CSW) who completed six months of ART and compare with the female general population (GP). Clinical records of CSW and GPs who initiated ART between December 2014 to December 2016 from seven urban clinics were analyzed to determine virologic suppression (viral load < 1000 copies/ml) and associated factors. We identified 218 CSW and 182 female GPs. CSW had median age of 28 (IQR 25-31) vs 31 (IQR 26-37); median baseline CD4 446 (IQR 308-696) vs 352 (IQR 164–493) cells/microL; and optimal ART adherence levels at 70.6% vs 92.8% respectively, compared to GP. Virologic suppression in CSW and GPs was 85.7% and 89.6% respectively, P=0.28. Overall virologic suppression in CSW was 55% while Retention in care after 6 months of ART was 77.5%. Immediate ART initiation (<2weeks) and tuberculosis independently predicted virologic suppression in CSW with adjusted odds ratios 0.07 (95% C.I. 0.01-0.55, P=0.01) and 0.09 (95% C.I. 0.01-0.96, P=0.046) respectively. Virologic suppression in both groups is similar, however, intensified follow-up is needed to improve treatment outcomes.