Successes and challenges in optimizing the viral load cascade to improve antiretroviral therapy adherence and rationalize second‐line switches in Swaziland

Abstract

IntroductionAs antiretroviral therapy (ART) is scaled up, more patients become eligible for routine viral load (VL) monitoring, the most important tool for monitoring ART efficacy. For HIV programmes to become effective, leakages along the VL cascade need to be minimized and treatment switching needs to be optimized. However, many HIV programmes in resource‐constrained settings report significant shortfalls.MethodsFrom a public sector HIV programme in rural Swaziland, we evaluated the VL cascade of adults (≥18 years) on ART from the time of the first elevated VL (>1000 copies/mL) between January 2013 and June 2014 to treatment switching by December 2015. We additionally described HIV drug resistance for patients with virological failure. We used descriptive statistics and Kaplan–Meier estimates to describe the different steps along the cascade and regression models to determine factors associated with outcomes.Results and DiscussionOf 828 patients with a first elevated VL, 252 (30.4%) did not receive any enhanced adherence counselling (EAC). Six hundred and ninety‐six (84.1%) patients had a follow‐up VL measurement, and the predictors of receiving a follow‐up VL were being a second‐line patient (adjusted hazard ratio (aHR): 0.72; p = 0.051), Hlathikhulu health zone (aHR: 0.79; p = 0.013) and having received two EAC sessions (aHR: 1.31; p = 0.023). Four hundred and ten patients (58.9%) achieved VL re‐suppression. Predictors of re‐suppression were age 50 to 64 (adjusted odds ratio (aOR): 2.02; p = 0.015) compared with age 18 to 34 years, being on second‐line treatment (aOR: 3.29; p = 0.003) and two (aOR: 1.66; p = 0.045) or three (aOR: 1.86; p = 0.003) EAC sessions. Of 278 patients eligible to switch to second‐line therapy, 120 (43.2%) had switched by the end of the study. Finally, of 155 successfully sequenced dried blood spots, 144 (92.9%) were from first‐line patients. Of these, 133 (positive predictive value: 92.4%) had resistance patterns that necessitated treatment switching.ConclusionsPatients on ART with high VLs were more likely to re‐suppress if they received EAC. Failure to re‐suppress after counselling was predictive of genotypically confirmed resistance patterns requiring treatment switching. Delays in switching were significant despite the ability of the WHO algorithm to predict treatment failure. Despite significant progress in recent years, enhanced focus on quality care along the VL cascade in resource‐limited settings is crucial.

Point‐of‐care viral load monitoring: outcomes from a decentralized HIV programme in Malawi

“…Previous reports from sub‐Saharan African settings have consistently shown low and delayed switching from first‐ to second‐line ART (even when VL‐monitoring is present), which have been linked to poorer treatment outcomes, increased mortality and the risk of the development and transmission of resistance . In our sites, 80% of first‐line treatment failures were switched to second‐line, an encouraging figure that is higher than in similar programmes (43%, Swaziland; 33%, Mozambique ). However, even 80% is insufficient.…”

“…Previous reports from sub-Saharan African settings have consistently shown low and delayed switching from first-to second-line ART (even when VL-monitoring is present), which have been linked to poorer treatment outcomes, increased mortality and the risk of the development and transmission of resistance [8,32,[60][61][62][63]. In our sites, 80% of first-line treatment failures were switched to second-line, an encouraging figure that is higher than in similar programmes (43%, Swaziland; 33%, Mozambique [50,64] three-test failure algorithm or the non-capture of VL-tests in the electronic database. Encouragingly, in 2016 MOH guidelines lowered the failure confirmation threshold from 5000 to 1000 cps/mL [45], and since 2018 follow-up VL-testing for suspect failures is independent of good adherence [46], thus further streamlining VL scale-up.…”

Feasibility of dried blood spots for HIV viral load monitoring in decentralized area in North Vietnam in a test-and-treat era, the MOVIDA project

“…Of those with confirmatory viral load, the majority were confirmed as failures. This is a lot more than usually observed [36], but could be explained by a selection bias from the clinical staff.…”

Long‐term virologic responses to antiretroviral therapy among HIV‐positive patients entering adherence clubs in Khayelitsha, Cape Town, South Africa: a longitudinal analysis

“…The primary outcomes of interest were the proportion of patients with i) an elevated VL and ii) confirmed virologic failure after AC entry. An elevated VL was defined as a VL >1000 copies/mL after AC entry [21]. Confirmed virologic failure was defined as two consecutive VLs >1000 copies/mL performed within a 12‐month window.…”