Adherence to antiretroviral therapy for HIV in sub-Saharan Africa and Asia: a comparative analysis of two regional cohorts

Our understanding of how to achieve optimal long-term adherence to antiretroviral therapy (ART) in settings where the burden of HIV disease is highest remains limited. We compared levels and determinants of adherence over time between HIV-positive persons receiving ART who were enrolled in a bi-regional cohort in sub-Saharan Africa and Asia. This multicentre prospective study of adults starting first-line ART assessed patient-reported adherence at follow-up clinic visits using a 30-day visual analogue scale. Determinants of suboptimal adherence ( <95%) were assessed for six-month intervals, using generalized estimating equations multivariable logistic regression with multiple imputations. Region of residence (Africa vs. Asia) was assessed as a potential effect modifier. Of 13,001 adherence assessments in 3934 participants during the first 24 months of ART, 6.4% (837) were suboptimal, with 7.3% (619/8484) in the African cohort versus 4.8% (218/4517) in the Asian cohort (p < 0.001). In the African cohort, determinants of suboptimal adherence were male sex (odds ratio (OR) 1.27, 95% confidence interval (CI) 1.06-1.53; p = 0.009), younger age (OR 0.8 per 10 year increase; 0.8-0.9; p = 0.003), use of concomitant medication (OR 1.8, 1.0-3.2; p = 0.044) and attending a public facility (OR 1.3, 95% CI 1.1-1.7; p = 0.004). In the Asian cohort, adherence was higher in men who have sex with men (OR for suboptimal adherence 0.6, 95% CI 0.4-0.9; p = 0.029) and lower in injecting drug users (OR for suboptimal adherence 1.6, 95% CI 0.9-2.6; p = 0.075), compared to heterosexuals. Risk of suboptimal adherence decreased with longer ART duration in both regions. Participants in low- and lower-middle-income countries had a higher risk of suboptimal adherence (OR 1.6, 1.3-2.0; p < 0.001), compared to those in upper-middle or high-income countries. Suboptimal adherence was strongly associated with virological failure, in Africa (OR 5.8, 95% CI 4.3-7.7; p < 0.001) and Asia (OR 9.0, 95% CI 5.0-16.2; p < 0.001). Patient-reported adherence barriers among African participants included scheduling demands, drug stockouts, forgetfulness, sickness or adverse events, stigma or depression, regimen complexity and pill burden. Psychosocial factors and health system resources may explain regional differences. Adherence-enhancing interventions should address patient-reported barriers tailored to local settings, prioritizing the first years of AR

Renal Dysfunction during Tenofovir Use in a Regional Cohort of HIV-Infected Individuals in the Asia-Pacific

<div><p>Background</p><p>In resource-limited settings, routine monitoring of renal function during antiretroviral therapy (ART) has not been recommended. However, concerns for tenofovir disoproxil fumarate (TDF)-related nephrotoxicity persist with increased use.</p><p>Methods</p><p>We investigated serum creatinine (S-Cr) monitoring rates before and during ART and the incidence and prevalence of renal dysfunction after starting TDF by using data from a regional cohort of HIV-infected individuals in the Asia-Pacific. Time to renal dysfunction was defined as time from TDF initiation to the decline in estimated glomerular filtration rate (eGFR) to <60 ml/min/1.73m² with >30% reduction from baseline using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or the decision to stop TDF for reported TDF-nephrotoxicity. Predictors of S-Cr monitoring rates were assessed by Poisson regression and risk factors for developing renal dysfunction were assessed by Cox regression.</p><p>Results</p><p>Among 2,425 patients who received TDF, S-Cr monitoring rates increased from 1.01 to 1.84 per person per year after starting TDF (incidence rate ratio 1.68, 95%CI 1.62–1.74, p <0.001). Renal dysfunction on TDF occurred in 103 patients over 5,368 person-years of TDF use (4.2%; incidence 1.75 per 100 person-years). Risk factors for developing renal dysfunction included older age (>50 vs. ≤30, hazard ratio [HR] 5.39, 95%CI 2.52–11.50, p <0.001; and using PI-based regimen (HR 1.93, 95%CI 1.22–3.07, p = 0.005). Having an eGFR prior to TDF (pre-TDF eGFR) of ≥60 ml/min/1.73m² showed a protective effect (HR 0.38, 95%CI, 0.17–0.85, p = 0.018).</p><p>Conclusions</p><p>Renal dysfunction on commencing TDF use was not common, however, older age, lower baseline eGFR and PI-based ART were associated with higher risk of renal dysfunction during TDF use in adult HIV-infected individuals in the Asia-Pacific region.</p></div

Factors associated with rates of serum creatinine monitoring after ART initiation.

<p>Factors associated with rates of serum creatinine monitoring after ART initiation.</p

Factors associated with time to renal dysfunction during TDF use.

<p>Factors associated with time to renal dysfunction during TDF use.</p

Crude rates of serum creatinine monitoring for each year on TDF.

<p>Crude rates of serum creatinine monitoring for each year on TDF.</p

Baseline demographics of patients who have ever received TDF.

<p>Baseline demographics of patients who have ever received TDF.</p