Laboratory Based Surveillance of HIV-1 Acquired Drug Resistance in Cameroon: Implications for Use of Tenofovir-Lamivudine-Dolutegravir (TLD) as Second- or Third-Line Regimens

Abstract

Increased HIV drug resistance (HIVDR) with antiretroviral therapy (ART) rollout may jeopardize therapeutic options, especially in this era of transition to fixed-dose tenofovir-lamivudine-dolutegravir (TLD). We studied acquired HIVDR (ADR) patterns and describe potentially active drugs after first- and second-line failure in resource-limited settings (RLS) like Cameroon. A laboratory-based study with 759 patients (≥15 years) experiencing virological failure was carried out at the Chantal Biya International Reference Centre (CIRCB), Yaoundé, Cameroon. Socio-demographic, therapeutic and immunovirological data from patient records were analysed according to HIV-1 genotypic profiles. Median (IQR) ART-duration was 63 (50–308) months. Median CD4 and viremia were 153 (IQR:50–308) cells/mm3 and 138,666 (IQR:28,979–533,066) copies/mL, respectively. Overall ADR was high (93.4% first-line; 92.9%-second-line). TDF, potentially active in 35.7% of participants after first-line and 45.1% after second-line, suggested sub-optimal TLD-efficacy in second-line (64.3%) and third-line (54.9%). All PI/r preserved high efficacy after first-line failure while only DRV/r preserved high-level efficacy (87.9%) after second-line failure. In this resource-limited setting (RLS), ADR is high in ART-failing patients. PI/r strategies remain potent backbones for second-line ART, while only DRV/r remains very potent despite second-line failure. Though TLD use would be preferable, blind use for second- and third-line regimens may be sub-optimal (functional monotherapy with dolutegravir) with high risk of further failure, thus suggesting strategies for selective ART switch to TLD in failing patients in RLS.

Retrospective Study on Genetic Diversity and Drug Resistance among People Living with HIV at an AIDS Clinic in Beijing

“…Unlike previous studies, our study observed an overall prevalence of ADR at 27.8%, which is significantly lower than the rates reported in Xi’an [ 17 ], Guangdong [ 35 ], and Portugal [ 36 , 37 ]. Consistent with the findings of numerous studies, EFV and NVP were found to be the most susceptible to drug resistance [ 35 , 36 ].…”

“…After excluding 145 ART-naive individuals without sequence results, the final analysis included 1640 ART-naive individuals for PDR analysis and 569 ARTexperienced individuals for ADR analysis. Among the 1640 ART-naive individuals, the median age was 31 years (interquartile range (IQR) [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. The majority of participants were male (97.0%, 1590/1640), while a smaller proportion were female (3.5%, 50/1640).…”

“…age was 31 years (interquartile range (IQR) [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. The majority of participants were male (97.0%, 1590/1640), while a smaller proportion were female (3.5%, 50/1640).…”