Switch to second-line versus continued first-line antiretroviral therapy for patients with low-level HIV-1 viremia: An open-label randomized controlled trial in Lesotho
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Alain Amstutz aff001; Bienvenu Lengo Nsakala aff004; Fiona Vanobberghen aff001; Josephine Muhairwe aff004; Tracy Renée Glass aff001; Tilo Namane aff005; Tlali Mpholo aff006; Manuel Battegay aff002; Thomas Klimkait aff007; Niklaus Daniel Labhardt aff001
Působiště autorů:
Swiss Tropical and Public Health Institute, Basel, Switzerland
aff001; University of Basel, Basel, Switzerland
aff002; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
aff003; SolidarMed, Partnerships for Health, Maseru, Lesotho
aff004; Motebang Government Hospital, Leribe, Lesotho
aff005; Senkatana HIV Clinic, Maseru, Lesotho
aff006; Molecular Virology, Department of Biomedicine, University of Basel, Basel, Switzerland
aff007
Vyšlo v časopise:
Switch to second-line versus continued first-line antiretroviral therapy for patients with low-level HIV-1 viremia: An open-label randomized controlled trial in Lesotho. PLoS Med 17(9): e32767. doi:10.1371/journal.pmed.1003325
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pmed.1003325
Souhrn
Background
Current World Health Organization (WHO) antiretroviral therapy (ART) guidelines define virologic failure as two consecutive viral load (VL) measurements ≥1,000 copies/mL, triggering empiric switch to next-line ART. This trial assessed if patients with sustained low-level HIV-1 viremia on first-line ART benefit from a switch to second-line treatment.
Methods and findings
This multicenter, parallel-group, open-label, superiority, randomized controlled trial enrolled patients on first-line ART containing non-nucleoside reverse transcriptase inhibitors (NNRTI) with two consecutive VLs ≥100 copies/mL, with the second VL between 100–999 copies/mL, from eight clinics in Lesotho. Consenting participants were randomly assigned (1:1), stratified by facility, demographic group, and baseline VL, to either switch to second-line ART (switch group) or continued first-line ART (control group; WHO guidelines). The primary endpoint was viral suppression (<50 copies/mL) at 36 weeks. Analyses were by intention to treat, using logistic regression models, adjusted for demographic group and baseline VL. Between August 1, 2017, and August 7, 2019, 137 individuals were screened, of whom 80 were eligible and randomly assigned to switch (n = 40) or control group (n = 40). The majority of participants were female (54 [68%]) with a median age of 42 y (interquartile range [IQR] 35–51), taking tenofovir disoproxil fumarate/lamivudine/efavirenz (49 [61%]) and on ART for a median of 5.9 y (IQR 3.3–8.6). At 36 weeks, 22/40 (55%) participants in the switch versus 10/40 (25%) in the control group achieved viral suppression (adjusted difference 29%, 95% CI 8%–50%, p = 0.009). The switch group had significantly higher probability of viral suppression across different VL thresholds (<20, <100, <200, <400, and <600 copies/mL) but not for <1,000 copies/mL. Thirty-four (85%) participants in switch group and 21 (53%) in control group experienced at least one adverse event (AE) (p = 0.002). No hospitalization or death or other serious adverse events were observed. Study limitations include a follow-up period too short to observe differences in clinical outcomes, missing values in CD4 cell counts due to national stockout of reagents during the study, and limited generalizability of findings to other than NNRTI-based first-line ART regimens.
Conclusions
In this study, switching to second-line ART among patients with sustained low-level HIV-1 viremia resulted in a higher proportion of participants with viral suppression. These results endorse lowering the threshold for virologic failure in future WHO guidelines.
Trial registration
The trial is registered at ClinicalTrials.gov, NCT03088241.
Klíčová slova:
Antiretroviral therapy – Hemoglobin – HIV – Cholesterol – Medical risk factors – Randomized controlled trials – Viral load – Viremia
Zdroje
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