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

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

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

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

Baseline characteristics of adults initiating cART at JOOTRH between January 2009 and January 2011.

<p>4 participants who were included in the study were on triple NRTI (ABC, NVP, EFV), while 7 (4 in the study and 3 who were lost to follow up) were on PI based regimen.</p

Predictors of cART modification.

<p>Hazard ratios and 95% confidence intervals of predictors for cART modification. Bolded values indicate independent predictors. d4T-Stavudine, TDF-Tenofovir, NVP-Nevirapine, AZT-Zidovudine, EFV-Efavirenz. *178 missing CD4 values were imputed by multiple imputation using chain equations.</p