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. 2025 May 9;5(1):164.
doi: 10.1038/s43856-025-00875-x.

HIV-1 suppression and rare dolutegravir resistance in antiretroviral-experienced people with HIV in Liberia

Affiliations

HIV-1 suppression and rare dolutegravir resistance in antiretroviral-experienced people with HIV in Liberia

James Soka Moses et al. Commun Med (Lond). .

Abstract

Background: Increasingly, persons with HIV in Liberia are receiving antiretroviral therapy containing the integrase strand-transfer inhibitor (InSTI) dolutegravir (DTG), but the prevalence of and factors associated with virologic failure and HIV drug resistance (HIVDR) remain unknown.

Methods: Cross-sectional analysis of 2019-2022 enrolment data from 1276 persons with HIV in the HONOR cohort included sociodemographic information, plasma viral loads (pVL), CD4 counts, and HIVDR testing by next generation sequencing in participants with virologic failure (pVL≥1000 copies/mL).

Results: Of the 1201 participants with pVL results, 72% are female and median age is 42 (interquartile range [IQR] 35-50) years. All are on ART (median 6.1 [2.1-11] years): 74% on DTG-based and 23% on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. Ninety (7.5%) had virologic failure; 970 (81%) are suppressed (<40 copies/mL). Virologic failure is less prevalent with DTG- versus NNRTI-based regimens (5.3% vs. 14%, adjusted prevalence ratio [aPR]=0.3, 95% confidence interval [CI] 0.2-0.5) and is associated with age <50 years, CD4 count <200 cells/µL, and hemoglobin <11 g/dL. In 70 participants with virologic failure and successful sequencing, HIVDR prevalence is 81% for any ARV, 5.7% for InSTIs, 79% for NNRTIs, and 61% for nucleos(t)ide reverse transcriptase inhibitors (NRTIs). Intermediate-to-high resistance to ≥1 NRTI in current ART is less prevalent with DTG+2NRTIs than NNRTI+2NRTIs regimens (aPR = 0.5, 95%CI 0.3-0.8).

Conclusions: Most participants in the cohort are virologically-suppressed. Among those with virologic failure, HIVDR prevalence is high to NRTIs and NNRTIs, but low to InSTIs. Ongoing evaluation is necessary to determine the durability of DTG-based ART.

Plain language summary

Antiretroviral therapy (ART) is a combination of medications used to treat people infected with human immunodeficiency virus (HIV). ART prevents HIV from replicating and so reduces the risk of a person infecting others with HIV. ART is recommended for all people with HIV in Liberia, but it is unknown how well people respond to treatment or whether the specific type of HIV they have is killed by ART. We measured the amount of HIV in some people on ART and whether the HIV they were infected with was killed by ART. Most people responded well to the treatment but people on ART containing the drug efavirenz were more likely than those taking dolutegravir not to respond. This information could be used to improve the combinations of medications used in ART to treat patients.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Major HIV mutational sequences in PWH with pVL pVL≥1000 copies/mL (N = 70).
The percentages of participants (x-axis) with HIV-1 sequences containing major drug resistance mutations (y-axis) are shown for those receiving non-dolutegravir (DTG)-based (red bars, N = 38) and DTG-based (black bars, N = 32) antiretroviral therapy. Not all listed mutations at a given position were detected. NRTI mutations not detected: S68del, T69ins/del, 0151L/M. NNRTI mutations not detected: F227C. INSTI mutations not detected: E92G/O/V, F121Y, G140A/C/R/S, Y143A/C/G/H/K/R/S, 0146P, S147G, 0148H/K/N/R, V151A/L, and N155H/S/T. PI mutations not detected: D3ON, V32I, 147A/V, G48A/L/M/O/S/T/V, I5OL/V, and L90M.

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