Risk factors for virological failure and subtherapeutic antiretroviral drug concentrations in HIV-positive adults treated in rural northwestern Uganda

ABSTRACT: BACKGROUND: Little is known about immunovirological treatment outcomes and adherence in HIV/AIDS patients on antiretroviral therapy (ART) treated using a simplified management approach in rural areas of developing countries, or about the main factors influencing those outcomes in clinical practice. METHODS: Cross-sectional immunovirological, pharmacological, and adherence outcomes were evaluated in all patients alive and on fixed-dose ART combinations for 24 months, and in a random sample of those treated for 12 months. Risk factors for virological failure (>1,000 copies/mL) and subtherapeutic antiretroviral (ARV) concentrations were investigated with multiple logistic regression. RESULTS: At 12 and 24 months of ART, 72% (n=701) and 70% (n=369) of patients, respectively, were alive and in care. About 8% and 38% of patients, respectively, were diagnosed with immunological failure; and 75% and 72% of patients, respectively, had undetectable HIV RNA (<400 copies/mL). Risk factors for virological failure (>1,000 copies/mL) were poor adherence, tuberculosis diagnosed after ART initiation, subtherapeutic NNRTI concentrations, general clinical symptoms, and lower weight than at baseline. About 14% of patients had low ARV plasma concentrations. Digestive symptoms and poor adherence to ART were risk factors for low ARV plasma concentrations. CONCLUSIONS: Efforts to improve both access to care and patient management to achieve better immunological and virological outcomes on ART are necessary to maximize the duration of first-line therapy

Incidence and predictors of first line antiretroviral regimen modification in western Kenya.

Limited antiretroviral treatment regimens in resource-limited settings require long-term sustainability of patients on the few available options. We evaluated the incidence and predictors of combined antiretroviral treatment (cART) modifications, in an outpatient cohort of 955 patients who initiated cART between January 2009 and January 2011 in western Kenya.cART modification was defined as either first time single drug substitution or switch. Incidence rates were determined by Poisson regression and risk factor analysis assessed using multivariate Cox regression modeling.Over a median follow-up period of 10.7 months, 178 (18.7%) patients modified regimens (incidence rate (IR); 18.6 per 100 person years [95% CI: 16.2-21.8]). Toxicity was the most common cited reason (66.3%). In adjusted multivariate Cox piecewise regression model, WHO disease stage III/IV (aHR; 1.82, 95%CI: 1.25-2.66), stavudine (d4T) use (aHR; 2.21 95%CI: 1.49-3.30) and increase in age (aHR; 1.02, 95%CI: 1.0-1.04) were associated with increased risk of treatment modification within the first year post-cART. Zidovudine (AZT) and tenofovir (TDF) use had a reduced risk for modification (aHR; 0.60 95%CI: 0.38-0.96 and aHR; 0.51 95%CI: 0.29-0.91 respectively). Beyond one year of treatment, d4T use (aHR; 2.75, 95% CI: 1.25-6.05), baseline CD4 counts ≤350 cells/mm3 (aHR; 2.45, 95%CI: 1.14-5.26), increase in age (aHR; 1.05 95%CI: 1.02-1.07) and high baseline weight >60kg aHR; 2.69 95% CI: 1.58-4.59) were associated with risk of cART modification.Early treatment initiation at higher CD4 counts and avoiding d4T use may reduce treatment modification and subsequently improve sustainability of patients on the available limited options

Antibiotic consumption and utilization at a large tertiary care level hospital in Uganda: A point prevalence survey.

IntroductionEffective antimicrobial stewardship programs require data on antimicrobial consumption (AMC) and utilization (AMU) to guide interventions. However, such data is often scarce in low-resource settings. We describe the consumption and utilization of antibiotics at a large tertiary-level hospital in Uganda.MethodsIn this cross-sectional study at Kiruddu National Referral Hospital, we analyzed medicine delivery records for the period July 2021 to June 2022, accessed on 12/08/2022, to extract AMC data expressed as defined daily doses (DDDs) per 1000 inhabitants per day (DID). We used the WHO point prevalence survey (PPS) to analyze AMU data with a systematic sampling of outpatient department (OPD) for a period between June and August 2022 and selected all inpatient department (IPD) patients admitted before 8:00 AM on 27/11/2022. AMU data was analyzed as the proportion of individual antibiotic prescriptions, indications for prescriptions, and compliance with the national treatment guidelines. Both AMC and AMU data were categorized by the WHO AWaRe (access, watch, and reserve) criteria.ResultsIn the year 2021-2022, a total of 6.05 DID of antibiotics were consumed comprising 3.61 DID (59.6%) access, 2.44 DID (40.3%) watch, and 0.003 (0.1%) reserve antibiotics. The most consumed antibiotics comprised penicillin (1.61 DID, 26.7%), cephalosporins (1.51, 25%), and imidazole (1.10 DID, 18.1%). A total of 119/211 (56%) patients in the OPD and 99/172 (57.5%) patients in the IPD were prescribed antibiotics. Of the 158 OPD antibiotic prescriptions, 73 (46.2%) were access, 72 (45.6%) were watch, 0 (0%) were reserve, and 13 (8.2%) were unclassified antibiotics. Of the 162 IPD antibiotic prescriptions, 62 (38.3%) were access, 88 (54.3%) were watch, 01 (0.6%) was reserve, and 11 (6.8%) were unclassified antibiotics. Indications for antibiotic prescriptions in the OPD comprised respiratory tract infections (53, 38.1%), urinary tract infections (34, 26.6%), gastrointestinal infections (20, 14.4%), sepsis (17, 12.2%), and medical prophylaxis (12, 8.7%). The indications for antibiotic prescriptions in the IPD comprised sepsis (28.2%), respiratory tract infections (18.3%), burn wounds (14.1%), and gastrointestinal infections (14.1%).ConclusionPrescription of watch antibiotics in both OPD and IPD hospital settings was high. Establishment of robust antimicrobial stewardship measures could help improve the rational prescription of antibiotics

Determinants of continuation on HIV pre-exposure propylaxis among female sex workers at a referral hospital in Uganda: a mixed methods study using COM-B model

Abstract Background Female sex workers (FSWs) have the highest HIV prevalence in Uganda. Pre-exposure prophylaxis (PrEP) has been recommended as a key component of the HIV combination prevention strategy. Although patient initiation of PrEP has improved, continuation rates remain low. This study evaluated PrEP continuation among FSWs and explored potential determinants of PrEP adherence within a public referral hospital in urban Uganda. Methods We conducted an explanatory sequential mixed method study at Kiruddu National referral hospital in Uganda. Secondary data on socio demographic characteristics and follow up outcomes of at least one year was collected for all FSWs who were initiated PrEP between May 2020 and April 2021 and data analyzed on July 15,2023. We used Kaplan–Meier survival analysis to evaluate continuation on PrEP from time of initiation and follow-up period. The capability, opportunity, and motivation to change behaviour model was used to explore perspectives and practices of FSWs (n = 24) and health care providers (n = 8) on continuation on PrEP among FSWs, using semi structured interviews. The qualitative data was deductively coded and analyzed thematically, categorizing the themes related to PrEP continuation as facilitators and barriers. Results Of the 292 FSWs initiated on PrEP, median age was 26 years (interquartile range, 21–29), 101 (34.6) % were active on PrEP, 137 (46.9%) were lost to follow-up, 45 (15.4%) were no longer eligible to continue PrEP, eight (2.7%) were transferred out and one (0.3%) had died. Median survival time on PrEP was 15 months (Interquartile range IQR, 3–21). The continuation rates on PrEP at six (6) and 12 months were 61.1% and 53.1%, respectively. Facilitators of PrEP continuation included awareness of risk associated with sex work, integration of PrEP with other HIV prevention services, presence of PrEP Peer support and use of Drop-in centers. The barriers included low community awareness about PrEP, high mobility of sex workers, substance abuse, and the unfavorable daytime clinic schedules. However, the quantitative findings from the multivariable Cox Proportional Hazards Model did not align with the reported findings for the qualitative evaluation. Conclusion Continuation on PrEP remains low among FSWs. Interventions for PrEP continuation should address barriers such as low community awareness of PrEP, substance abuse and restrictive health facility policies for scale of the PrEP program among FSWs in Uganda. Integration of PrEP with other services and scale up of community PrEP delivery structures may improve its continuation

Mortality and associated factors among people living with HIV admitted at a tertiary-care hospital in Uganda: a cross-sectional study

Abstract Background Hospital admission outcomes for people living with HIV (PLHIV) in resource-limited settings are understudied. We describe in-hospital mortality and associated clinical-demographic factors among PLHIV admitted at a tertiary-level public hospital in Uganda. Methods We performed a cross-sectional analysis of routinely collected data for PLHIV admitted at Kiruddu National Referral Hospital between March 2020 and March 2023. We estimated the proportion of PLHIV who had died during hospitalization and performed logistic regression modelling to identify predictors of mortality. Results Of the 5,827 hospitalized PLHIV, the median age was 39 years (interquartile range [IQR] 31–49) and 3,293 (56.51%) were female. The median CD4 + cell count was 109 cells/µL (IQR 25–343). At admission, 3,710 (63.67%) were active on antiretroviral therapy (ART); 1,144 (19.63%) had interrupted ART > 3 months and 973 (16.70%) were ART naïve. In-hospital mortality was 26% (1,524) with a median time-to-death of 3 days (IQR 1–7). Factors associated with mortality (with adjusted odds ratios) included ART interruption, 1.33, 95% confidence intervals (CI) 1.13–1.57, p 0.001; CD4 + counts ≤ 200 cells/µL 1.59, 95%CI 1.33–1.91, p  20 km from hospital 1.23, 95%CI 1.04–1.46, p 0.014; hospital readmission 0.7, 95%CI 0.56–0.88, p 0.002; chronic lung disease 0.62, 95%CI 0.41–0.92, p 0.019; and neurologic disease 0.46, 95%CI 0.32–0.68, p < 0.001. Conclusion One in four admitted PLHIV die during hospitalization. Identification of risk factors (such as ART interruption, function impairment, low/undocumented CD4 + cell count), early diagnosis and treatment of co-infections and liver disease could improve outcomes

Reasons of first-time antiretroviral treatment modification among 955 patients initiating first-line regimen in JOOTRH in western Kenya between January 2009 and January 2011.

<p>Reasons of first-time antiretroviral treatment modification among 955 patients initiating first-line regimen in JOOTRH in western Kenya between January 2009 and January 2011.</p

Toxicity rates of cART modification per 100 person years for individual antiretroviral regimen.

<p>Toxicity rates of cART modification per 100 person years for individual antiretroviral regimen.</p

Kaplan Meier plots showing time to cART modification:overall and by key reasons of cART modifications.

<p>Kaplan Meier plots showing time to cART modification:overall and by key reasons of cART modifications.</p