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BACKGROUND: HIV-1 plasma viral load (pVL) is the key indicator to monitor the response to combination antiretroviral therapy. pVL of <1000 copies/mL is considered as the threshold for virological suppression (VS) by national (India) and WHO guideline. A subset of people who have attained VS experience low-level viremia (LLV- pVL 40-999 copies/mL); its overall impact on clinical outcome is largely unknown.
METHODS: We conducted a longitudinal retrospective analysis of 3498 participants visiting YRGCARE, Chennai, India between 2013-2018. The participants were on ART for =6 months with =2 pVL measurements. We stratified results for those with pVL <1000 copies/mL as follows: Fully suppressed (FS) – pVL <40 copies/mL, LLV-I – pVL 40-199 copies/mL, LLV-II – pVL 200-399 copies/mL, and LLV-III-pVL 400-999 copies/mL. The primary outcome of the study was virological failure (VF) – pVL >1000 copies/mL. Multivariable Cox regression estimated was used to find the association with VF.
RESULTS: The median age was 44 years (IQR 38-50 years), 60% were male, 2574 (73.6%) were on 1st-line, 865 (24.7%) were on 2nd-line, and 59 (1.7%) were on both (BL). The median follow-up duration was 111.28 weeks (IQR 63.4-169.9 weeks). There were 2965 FS (84.8%) and 533 (15.2%) LLV, which includes 225 LLV-I, 130 LLV-II, and 178 LLV-III. 360 of 533 LLV had multiple LLV episodes. During the follow-up, 343 (9.8%) experienced VF, with 217 (6.2%) having it after LLV (41% of LLV) and 126 (3.6%) having it after FS (4.3% of FS). When compared to suppressed, LLV had a greater risk of VF (HR 12.7; 95% CI 10.2-15.9). 1st-line participants had a higher incidence of VF (HR 15.8, 95% CI 11.4-21.9) than 2nd-line (HR 5.6, 95% CI 4.1- 7.7). LLV-III had the highest risk of VF [(HR 22.856, 95% CI 15.204-34.359) vs. (HR 8.186, 95% CI 5.564-12.043)], followed by LLV-II [(HR 13.375; 95% CI 8.327-21.483) vs. (HR 6.261; 95% CI 4.044-9.695)])] and LLV-I [(HR 12.976; 95% CI 7.974-21.118) vs. (HR 4.158; 95% CI 2.826-6.119)] in 1st-line vs. 2nd-line respectively.
CONCLUSIONS: LLV was associated for higher risk of VF. Close monitoring of individuals experiencing LLV may help in early identification of VF, thus preventing drug resistance.

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