Prevalence and factors associated with low-level viremia among PLHIV substituted to Dolutegravir from non-nucleotide reverse transcriptase inhibitors at Kitebi Health Center III

Abstract

Introduction: Globally, 38.4 million people were living with HIV by the end of 2021, and about two-thirds of this population were in the sub-Saharan region. Effective adherence to combination antiretroviral therapy (ART) suppresses the virus to undetectable levels. In Uganda, a rise in the pre-treatment drug resistance among people living with HIV (PLHIV) on first line ART regimen led to the substitution of the non-nucleoside reverse transcriptase inhibitors (NNRTIs) with dolutegravir (DTG) due to its superior viral suppression, lower drug interaction potential, and higher genetic barrier to resistance. However, despite the good efficacy, some PLHIV substituted to DTG exhibit low level viremia (LLV), that could be as a result of the unrecognized partial resistance within the nucleoside reverse transcriptase (NRTI) back bone regimen. LLV is associated with the development of drug resistance and virologic failure which eventually increases the risk of spreading the virus and hence threatening epidemic control measures. General objective: To determine the prevalence and factors associated with LLV among PLHIV who substituted from NNRTIs to DTG-based first-line regimen at Kitebi Health Centre. Methods: This was a retrospective longitudinal study done at the HIV clinic of Kitebi Health Centre and 813 participants were systematically sampled. Data were extracted from participant treatment charts into a data abstraction tool before being entered into Epi-Info and was later analyzed with Stata version 15. Generalized estimating equations and a logit-link to binomial were used for data analysis. Results: The prevalence of LLV was 3.9% (95% CI 2.6 - 5.3) within the 3 years of observation following the substitution to a DTG-based regimen. The factors associated with LLV among the participants were; Time [aOR= 8.34, 95% CI (1.71-40.60)], baseline WHO stage 3&4 * Time [aOR= 0.26, 95% CI (0.08-0.89)], short duration on DTG [aOR= 0.85, 95% CI (0.74-0.97)], previous LLV before substitution to DTG, [aOR= 2.76, 95% CI (1.30-5.86)]. The male sex complicated the relationship between Baseline WHO stage and occurrence of LLV after substitution to DTG. Among the participants who experienced LLV, 81.3% (26) eventually suppressed their viral loads on subsequent viral load assessment, 15.6% (5) progressed to persistent LLV and only 3.1% (1) progressed to virologic failure. Conclusion: The prevalence of LLV among adult PLHIV substituted to DTG from NNRTIs was low and most patients subsequently suppressed the virus following a LLV. However, 1 in 6 patients progressed to persistent LLV while 3 in 100 patients progressed to virologic failure. Patients with LLV should be monitored more closely over time especially focusing on the risky groups like those WHO stage 3 or 4 illness and prior LLV before substitution. Special consideration for HIV drug resistance testing among PLHIV with persistent LLV is recommended to the Ministry of Health.