Low-Level Viremia among Adults Living with HIV on Dolutegravir-Based First-Line Antiretroviral Therapy Is a Predictor of Virological Failure in Botswana

Author:

Bareng Ontlametse T.12,Moyo Sikhulile1345ORCID,Mudanga Mbatshi6,Sebina Kagiso6,Koofhethile Catherine K.13,Choga Wonderful T.12,Moraka Natasha O.12ORCID,Maruapula Dorcas1ORCID,Gobe Irene2,Motswaledi Modisa S.2,Musonda Rosemary1,Nkomo Bornapate7,Ramaabya Dinah7,Chebani Tony7,Makuruetsa Penny7,Makhema Joseph13,Shapiro Roger13,Lockman Shahin138,Gaseitsiwe Simani13

Affiliation:

1. Botswana Harvard Health Partnership, Gaborone 0000, Botswana

2. Department of Medical Sciences, Faculty of Allied Health Professions, University of Botswana, Gaborone 0022, Botswana

3. Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA

4. Department of Pathology, Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7935, South Africa

5. School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria 0028, South Africa

6. Department of Strategic Information, Botswana-University of Maryland School of Medicine Health Initiative, Gaborone 0022, Botswana

7. Botswana Ministry of Health, Gaborone 0038, Botswana

8. Division of Infectious Diseases, Brigham & Women’s Hospital, Boston, MA 02115, USA

Abstract

We evaluated subsequent virologic outcomes in individuals experiencing low-level virem ia (LLV) on dolutegravir (DTG)-based first-line antiretroviral therapy (ART) in Botswana. We used a national dataset from 50,742 adults who initiated on DTG-based first-line ART from June 2016–December 2022. Individuals with at least two viral load (VL) measurements post three months on DTG-based first-line ART were evaluated for first and subsequent episodes of LLV (VL:51–999 copies/mL). LLV was sub-categorized as low-LLV (51–200 copies/mL), medium-LLV (201–400 copies/mL) and high-LLV (401–999 copies/mL). The study outcome was virologic failure (VF) (VL ≥ 1000 copies/mL): virologic non-suppression defined as single-VF and confirmed-VF defined as two-consecutive VF measurements after an initial VL < 1000 copies/mL. Cox regression analysis identified predictive factors of subsequent VF. The prevalence of LLV was only statistically different at timepoints >6–12 (2.8%) and >12–24 (3.9%) (p-value < 0.01). LLV was strongly associated with both virologic non-suppression (adjusted hazards ratio [aHR] = 2.6; 95% CI: 2.2–3.3, p-value ≤ 0.001) and confirmed VF (aHR = 2.5; 95% CI: 2.4–2.7, p-value ≤ 0.001) compared to initially virally suppressed PLWH. High-LLV (HR = 3.3; 95% CI: 2.9–3.6) and persistent-LLV (HR = 6.6; 95% CI: 4.9–8.9) were associated with an increased hazard for virologic non-suppression than low-LLV and a single-LLV episode, respectively. In a national cohort of PLWH on DTG-based first-line ART, LLV > 400 copies/mL and persistent-LLV had a stronger association with VF. Frequent VL testing and adherence support are warranted for individuals with VL > 50 copies/mL.

Funder

Fogarty International Center at the US National Institutes of Health

Sub-Saharan African Network for TB/HIV Research Excellence

H3ABioNet

US National Institutes of Health NIH

US National Institutes of Health Common Fund

Trials of Excellence in Southern Africa

Publisher

MDPI AG

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3. U.S. Department of Health and Human Services (2024, March 01). Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV, Available online: https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines.

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