Third‐line antiretroviral therapy, including raltegravir (RAL), darunavir (DRV/r) and/or etravirine (ETR), is well tolerated and achieves durable virologic suppression over 144 weeks in resource‐limited settings: ACTG A5288 strategy trial

Abstract

Introduction: ACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second-line protease inhibitor (PI)-based antiretroviral therapy (ART) from 10 low-and middle-income countries (LMICs). Participants resistant to lopinavir (LPV) and/or multiple nucleotide reverse transcriptase inhibitors started on third-line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) and/or etravirine (ETR) according to their resistance profiles. At 48 weeks, 87% of these participants achieved HIV-1 RNA ≤200 copies/ml. We report here long-term outcomes over 144 weeks. Methods: Study participants were enrolled from 2013 to 2015, prior to the availability of dolutegravir in LMICs. "Extended Follow-up" of the study started after the last participant enrolled had reached 48 weeks and included participants still on antiretroviral (ARV) regimens containing RAL, DRV/r and/or ETR at that time. RAL, DRV/r and ETR were provided for an additional 96 weeks (giving total follow-up of ≥144 weeks), with HIV-1 RNA measured at 48 and 96 weeks and CD4 count at 96 weeks after entry into Extended Follow-up. Proportion of participants with HIV-1 RNA ≤200 copies/ml was estimated every 24 weeks, using imputation if necessary to handle the different measurement schedule in Extended Follow-up; mean CD4 count changes were estimated using loess regression. Results and Discussion: Of 257 participants (38% females), at study entry, median CD4 count was 179 cells/mm 3 , and HIV-1 RNA was 4.6 log 10 copies/ml. Median follow-up was 168 weeks (IQR: 156-204); 15 (6%) participants were lost to follow-up and 9 (4%) died. 27/246 (11%), 26/246 (11%) and 13/92 (14%) of participants who started RAL, DRV/r and ETR, respectively, discontinued these drugs; only three due to adverse events. 87%, 86%, 83% and 80% of the participants had HIV-1 RNA ≤200 copies/ml at weeks 48, 96, 144 and 168 (95% CI at week 168: 74-85%), respectively. Mean increase from study entry in CD4 count at week 168 was 265 cells/mm 3 (95% CI 247-283). Conclusions: Third-line regimens comprising of RAL, DRV/r and/or ETR were very well tolerated and had high rates of durable virologic suppression among PLWH in LMICs who were failing on second-line PI-based ART prior to the availability of dolutegravir.

Development and emerging trends of drug resistance mutations in HIV: a bibliometric analysis based on CiteSpace

“…If second-line therapy fails, third-line therapy needs to be attempted. One such medication combination that has been proven to be well tolerated is raltegravir, darunavir, and etravirine ( Avihingsanon et al, 2022 ). Additionally, a better second-line alternative is a wise decision for clinical trials ( Keene et al, 2021 ).…”

Relationship between self‐efficacy and adherence to antiretroviral therapy in HIV/AIDS patients: An analytical cross‐sectional study in southern Iran

“…The questionnaire was rated on a 5-point Likert-type scale ranging from very high to no effect. The sections of personal barriers, medication challenges, quality of service delivery, financial problems, perceived support, and disease disclosure included, respectively, eight items (range of 8-40), six items (range of 6-30), six items (range of 6-30), two items (range of 2-10), four items (range of 4-20), and four items (range of [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Validity and reliability of the questionnaire were previously substantiated.…”

“…It involves the initiation of treatment, implementation, and continuation with the recommended dose 10 . ART is crucial for a successful HIV treatment, as it has dramatically reduced viral transmission, disease progression, and mortality among HIV patients 11,12 …”

“…10 ART is crucial for a successful HIV treatment, as it has dramatically reduced viral transmission, disease progression, and mortality among HIV patients. 11,12 However, in Iran, it was estimated that only 20% of HIV patients were adherent to ART. 4 Studies have shown that poor adherence to medication in low-and middle-income countries is influenced by a lack of knowledge, negative attitudes, and negative beliefs.…”

Comparison of Markov Model and Dynamic Model in Economic Evaluations for Infectious Diseases: A case of Bictegravir/emtricitabine/tenofovir Treatment-native adults of HIV-1 in China

“…Discontinuation of ART was classi ed as virological (drug resistance) and non-virological (mainly adverse reactions) reasons. The discontinuation rates for each ART regimen were derived from relevant literature, including trial data [4,5,18,[29][30][31][32][33], with speci c details presented in Table 1. During the period of discontinuation, the CD4 cell counts of HIV patients decreased by 4.3 cells/mm 3 each month [34].…”