First‐line antiretroviral therapy durability in a 10‐year cohort of naïve adults started on treatment in Uganda

Abstract

IntroductionThe majority of studies from resource-limited settings only report short-term virological outcomes of patients on antiretroviral treatment (ART). We aim to describe the long-term durability of first-line ART and identify factors associated with long-term virological outcomes.MethodsAt the Infectious Diseases Institute in Kampala, Uganda, 559 adult patients starting ART in 2004 were enrolled into a research cohort and monitored with viral load (VL) testing every six months for 10 years. We report the proportion and cumulative probability of 1) achieving virologic suppression (at least one VL <400 copies/ml); 2) experiencing virologic failure in patients who achieved suppression (two consecutive VLs >1000 copies/ml or one VL >5000, for those without a subsequent one); 3) treatment failure (not attaining virologic suppression or experiencing virologic failure). We used Cox regression methods to determine the characteristics associated with treatment failure. We included gender, baseline age, WHO stage, body mass index, CD4 count, propensity score for initial ART regimen, VL, time-dependent CD4 count and adherence.ResultsOf the 559 patients enrolled, 472 (84.8%) had at least one VL (67 died, 13 were lost to follow-up, 4 transferred, 2 had no VL available); 73.6% started on d4T/3TC/nevirapine and 26.4% on AZT/3TC/efavirenz. Patients in the two groups had similar characteristics, except for the higher proportion of patients in WHO Stage 3/4 and higher VL in the efavirenz-based group. Four hundred thirty-nine (93%) patients achieved virologic suppression with a cumulative probability of 0.94 (confidence interval (CI): 0.92–0.96); 74/439 (16.9%) experienced virologic failure with a cumulative probability of 0.18 (CI: 0.15–0.22). In the multivariate analysis, initial d4T/3TC/nevirapine regimen (hazard ratio (HR): 3.02; CI: 3.02 (1.66–5.44, p<0.001)) and baseline VL ≥5 log10 copies/ml (HR: 2.29; CI: 1.29–4.04) were associated with treatment failures; patients of older age (HR: 0.87 per five-year increase; CI: 0.77–0.99), with adherence >95% (HR: 0.04; CI: 0.02–0.11) and with higher time-dependent CD4 count (HR: 0.94 per 50 cells/µl increase; CI: 0.92–0.99, p<0.001) were less likely to experience treatment failure.ConclusionsThe long-term virological outcomes from this cohort are promising and comparable to those from research-rich settings. Our results provide further evidence that efavirenz is associated with better virological outcomes.

Incidence and Predictors of First Line Anti-Retroviral Therapy Failure among Adults Receiving HIV Care in North West Ethiopia: A Hospital-Based Follow-Up Study

“…Study by Bayu, et al from Ethiopia stated that treatment failure was 3-fold and 7-fold increase in those who took ART for 2-4 years and > 4 years respectively as compared to those who took ART < 2 years period [11]. The risk of treatment failure continued to steadily increase with longer treatment duration, possibly explained by decline in adherence rate with time, a phenomenon known as 'treatment fatigue' [4,7,11].…”

“…This finding was consistent with studies conducted in Ethiopia (AHR (95% CI: 1.86-19.80) = 5.68)), Kenya (AHR (95% CI: 2.20-3.49) = 2.77)) South Africa (AHR (95% CI: 2.13-2.91) = 2.49)) and Uganda (AHR (95% CI: 2.3-11.05) = 5.05)) [7][8][9]12,15]. In fact adherence issue is the pillar for ART users.…”

“…African studies reported incidence of ART failure ranged from 0.96-5.88 per 100 person-year of observation (PYO) [3][4][5]. Documented predictors of treatment failure in Africa include, but not restricted to, younger or older age, male gender, low educational status, high pretreatment viral load, low pretreatment CD 4 count, low base line BMI, advanced HIV disease (WHO clinical stage 3 and 4), presence of opportunistic infections, TB co-infection, type of ART regimen, ART drug toxicities, drug-drug interactions, and inadequate ART adherence [3][4][5][6][7][8][9].…”

HIV-1 Drug Resistance Among Ugandan Adults Attending an Urban Out-Patient Clinic

“…The high proportion of patients virologically suppressed on first-line treatment is in line with findings from other studies previously conducted at the IDI. 20 To maintain a high rate of virological suppression, the clinic adopted several differentiated care models, such as the nurse-visit or pharmacy-refill program. 21 In both models, task shifting enables clinicians to concentrate on challenging cases.…”

Long-term durability of HIV viral load suppression

“…Although adherence to treatment and clinical follow-up in HIV patients in sub-Saharan Africa are affected by socioeconomic factors, drug availability has improved substantially. As a result, studies in the region are now reporting long-term viral suppression 10 that is comparable to that in developed countries, 11 and can be improved further with new approaches to adherence counselling. 12 As O'Connor and colleagues note, the high rates of viral rebound after initial suppression in black Africans who have migrated to the UK are difficult to explain with certainty, but they might be related to socioeconomic and psychosocial factors such as homelessness, substance abuse, and mental health issues that were not measured in their study.…”