HIV virologic response, patterns of drug resistance mutations and correlates among adolescents and young adults: A cross-sectional study in Tanzania

Abstract

Background The emergence of HIV drug resistance mutations (DRMs) is of significant threat to achieving viral suppression (VS) in the quest to achieve global elimination targets. We hereby report virologic outcomes and patterns of acquired DRMs and its associated factors among adolescents and young adults (AYA) from a broader HIV drug resistance surveillance conducted in Tanzania. Methods Data of AYA was extracted from a cross-sectional study conducted in 36 selected facilities using a two-stage cluster sampling design. Dried blood spot (DBS) samples were collected and samples with a viral load (VL) ≥1000 copies/mL underwent genotyping for the HIV-1 pol gene. Stanford HIV database algorithm predicted acquired DRMs, Fisher’s exact test and multivariable logistic regression assessed factors associated with DRMs and VS, respectively. Findings We analyzed data of 578 AYA on antiretroviral therapy (ART) for 9–15 and ≥ 36 months; among them, 91.5% and 88.2% had VS (VL<1000copies/mL) at early and late time points, respectively. Genotyping of 64 participants (11.2%) who had VL ≥1000 copies/ml detected 71.9% of any DRM. Clinically relevant DRMs were K103N, M184V, M41L, T215Y/F, L210W/L, K70R, D67N, L89V/T, G118R, E138K, T66A, T97A and unexpectedly absent K65R. Participants on a protease inhibitor (PI) based regimen were twice as likely to not achieve VS compared to those on integrase strand transfer inhibitors (INSTI). The initial VL done 6 months after ART initiation of ≥1000copies/mL was the primary factor associated with detecting DRMs (p = .019). Conclusions VS amongst AYA is lower than the third UNAIDs target. Additionally, a high prevalence of ADR and high levels of circulating clinically relevant DRMs may compromise the long-term VS in AYA. Furthermore, the first VL result of ≥1000copies/ml after ART initiation is a significant risk factor for developing DRMs. Thus, strict VL monitoring for early identification of treatment failure and genotypic testing during any ART switch is recommended to improve treatment outcomes for AYA.

Viral Load Suppression and Associated Factors Among Hiv-Infected Patients on Second-Line Antiretroviral Therapy at Public Health Facilities of West Guji, Guji and Borena Zones, Southern Ethiopia: Facility Based Cross-Sectional Study

“…This finding is consistent with studies conducted in the Ehlanzeni district of South Africa (74%), Uganda (75.8%), Kumasi, Ghana (76.1%), and the East Shewa zone of Oromia, Ethiopia (72%)(13–16). However, this finding is lower than those of studies conducted in the USA (86%)(17), Buenos Aires, Argentina (87.3%)(18), Cameroon (88.2% and 94.55%)(19, 20), Uganda (81%, 85%, & 85.7%)(21–23), Bamako, Mali (100%)(24), Mazowe, Zimbabwe (94.4%)(25), Tanzania (91.5%)(26), South Africa (77% and 77.2%)(27, 28), Kenya (80% and 90%) (29, 30), Ethiopia (82% and 82.39%) (10, 31). The ambitious 95-95-95 approach put forth by USAID, WHO, and UNAIDS to achieve 95% viral load suppression by 2030 is too far from the current results (5, 32).…”

Prevalence and predictors of persistent low-level HIV viraemia: a retrospective cohort study among people receiving dolutegravir-based antiretroviral therapy in Southern Nigeria

“…Our study found no associations between PLLV and age or sex, which is consistent with previous research that reported no links between client demographics and PLLV. 11 , 13 , 72 – 74 The absence of correlation between PLLV and individuals’ most recent World Health Organization clinical stage suggests that dolutegravir-based ART is effective in achieving and maintaining viral suppression in most clients, regardless of their demographic or clinical characteristics. 75 , 76 Also, the consistency of PLLV outcomes irrespective of the Differentiated Service Delivery model lends credibility to reports that Differentiated Service Delivery does not compromise the virological efficacy of dolutegravir-based ART.…”

Dolutegravir resistance in three pregnant and breastfeeding women in South Africa

“… 20 It is noteworthy that Case 2 re-engaged with each pregnancy, a common pattern of re-engagement among female patients. 21 Unfortunately, with increasing reports of DTG resistance, 9 , 10 clinicians in South Africa need to be aware that, although DTG is robust, resistance remains a possibility in a small proportion of individuals. This case series adds to the evidence raising concerns that in programmatic settings, DTG resistance may be more frequent than predicted, particularly in contexts where inadequate adherence support and VL monitoring result in prolonged periods of viral non-suppression.…”

“…However, within programmatic settings, reports of DTG resistance are emerging, including a 5.8% rate of DTG-resistant mutations among adolescents and young adults in a Tanzanian national survey. 9 A recent article also described South Africa’s first published case of DTG resistance, in a treatment-experienced, integrase strand inhibitor (InSTI)-naïve adolescent. 10 …”

“…8 However, within programmatic settings, reports of DTG resistance are emerging, including a 5.8% rate of DTG-resistant mutations among adolescents and young adults in a Tanzanian national survey. 9 A recent article also described South Africa's first published case of DTG resistance, in a treatment-experienced, integrase strand inhibitor (InSTI)-naïve adolescent. 10 The use of antiretroviral drugs that rapidly and safely achieve and sustain maternal viral suppression during pregnancy and breastfeeding is essential for vertical transmission prevention (VTP).…”