Abstract
Early identification of confirmed virological failure is paramount to avoid accumulation of drug resistance in patients on antiretroviral therapy (ART). Scale-up of HIV-RNA monitoring in Africa and timely switch to second-line regimens are challenged. A WHO adapted confirmed virological treatment screening algorithm (HIV-RNA screening, enhanced adherence counselling, confirmatory HIV-RNA testing) was evaluated in HIV-infected patients on first-line ART from Tanzania. The main endpoints included viral resuppression and virological failure rates, retention and turnaround time of the screening algorithm until second-line ART initiation. Secondary endpoints included risk factors for virological treatment failure and patterns of genotypic drug resistance. HIV-RNA >1000 copies/ml at first screening was detected in 58/356 (16.3%) patients (median time-on-treatment 6.3years, 25% immunological treatment failure). Adjusted risk factors for virological failure were age <30years (RR 5.2 [95% CI: 2.5-10.8]), years on ART ≥3years (RR 3.0 [1.0-8.9]), CD4-counts <200 cells/µl (RR 9.3 [4.0-21.8]) and poor self-reported treatment adherence (RR 2.0 [1.2-3.4]). Resuppression of HIV-RNA <1000 copies/ml was observed in 5/50 (10%) cases after enhanced adherence counselling. Confirmatory testing within 3months was performed in only 46.6% and switch to second-line ART within 6months in 60.4% of patients. Major NNRTI-mutation were detected in all of 30 patients, NRTI mutations in 96.7% and ≥3 thymidine-analogue mutations in 40%. No remaining NRTI options were predicted in 57% and limited susceptibility in 23% of patients. We observed low levels of viral resuppression following adherence counselling, associated with high levels of accumulated drug resistance. High visit burden and turnaround times for confirmed virological failure diagnosis further delayed switching to second-line treatment which could be improved using novel point-of-care viral load monitoring systems.
Highlights
In recent years, the coverage of antiretroviral treatment (ART) in sub-Saharan Africa has rapidly expanded and led to effective declines in HIV-infected patients’morbidity and mortality
63.2% were in WHO stage III/IV disease, the median CD4 count was 331/μl, 24.7% met the criterion for immunological treatment failure, the majority were on a zidovudine, lamivudine plus nevirapine or efavirenz-containing regimen with a median duration on first-line ART of 6.3 years
The proportion of patients still on a zidovudine-containing NRTI backbone was overrepresented in our cohort, which was explained by the long-term first-line duration for most of our patients, and the predominant NRTI backbone recommended at the time when ART was initiated
Summary
The coverage of antiretroviral treatment (ART) in sub-Saharan Africa has rapidly expanded and led to effective declines in HIV-infected patients’morbidity and mortality. In Tanzania, the reported national adult HIV prevalence was 5% by 2016, and among the estimated 1.4 million. The number of patients in sub-Saharan Africa with first-line treatment failure in need of second-line ART is increasing and was recently predicted to reach 0.5–3 million patients by 2030 [4]. There are several reports that in the presence of immunological and clinical treatment failure a switch to second-line ART is often not performed, which might be due to uncertainties about the predictive value of CD4 count-based failure criteria, suspected lack of treatment adherence, negligence or unavailability of previous CD4 values [8,9]. Untreated subsequent virological treatment failure accumulates the amount of acquired drug resistance mutations in the long term [10] and increases the risk of transmitted drug resistance [11]
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