Antiretroviral Therapy in Children and Adolescents: A Look Into Modern Single Tablet Regimens
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SUBMITTER: Lee C
PROVIDER: S-EPMC8591998 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Combined antiretroviral therapy (cART) has evolved considerably over the past decades leading to a better control of human immunodeficiency virus replication. Recently, regimens have evolved so as to simplify dosing frequency and reduce pill burden to improve adherence. Several national and international guidelines suggest antiretroviral (ARV) regimen simplification as a method of improving adherence. Decreased cART adherence has been associated with both patient-related factors and regimen-related factors. Adherence rates are statistically higher when simpler, once-daily (OD) regimens are combined with smaller daily regimen pill burdens. The avoidance of selective non-adherence, where a patient takes part of a regimen but not the full regimen, is a further potential benefit offered by single-tablet regimens (STRs). Simplification of cART has been associated with a better quality of life (QoL). Although tempered by other factors, better adherence, higher QoL and patients' preferences are all key points which might combine to assure long-lasting efficacy and durability of cART. All studies underlined the favorable tolerability profile of newer STRs. Three STRs are currently available. Tenofovir (TDF) plus emtricitabine (FTC)/efavirenz (EFV) was the first OD complete ARV regimen available as a STR. TDF plus FTC/rilpivirine is a second-generation STR. The most recently approved STR, TDF plus FTC/cobicistat/elvitegravir, is the first non-nucleoside reverse transcriptase inhibitor-based STR. All of them have shown excellent efficacy; safety and tolerability have been improved by more recent formulations. Several other STRs are anticipated both combining completely different drugs, abacavir (ABC) plus lamivudine (3TC)/dolutegravir, utilizing innovative formulations of older drugs, tenofovir alafenamide fumarate, or taking advance of bioequivalent drugs, lamivudine (3TC) plus ABC/EFV. The future challenge would be to develop completely alternative STRs (including for example protease inhibitors or new molecules) to extend the advantages of simplicity to heavily pre-treated individuals.
| S-EPMC4108118 | biostudies-literature
Project description:We determined risk of virologic failure (VF) in individuals initiating tenofovir/emtricitabine/efavirenz as single versus multiple tablet regimens (MTR). We found no significant difference in the risk of VF, though did observe a trend toward more VF and M184?V mutations among persons initiating MTR. Temporal trends in care may have confounded results.
| S-EPMC5411186 | biostudies-literature
Project description:ObjectivesPill burden during antiretroviral treatment (ART) is associated with worse adherence and impaired virological suppression. We compared the effectiveness, tolerance, and persistence on treatment of single tablet regimens (STRs) with non-STR once-daily regimens in patients receiving first-line ART.MethodsRetrospective analysis of naïve HIV-1 infected patients prospectively enrolled in the French Dat'AIDS cohort and initiating first-line ART with STRs or once-daily non-STRs from 2004 to 2013. The primary outcome was time to treatment discontinuation defined by any change in the treatment regimen. STR and non-STR groups were compared controlling for baseline risk factors by inverse probability weighted treatment Cox analysis (IPWT) and propensity-score matching (PSM).ResultsOverall, 3212 patients (STR 499, non-STR 2713) were included. Median time to treatment discontinuation was shorter in non-STR patients than in STR patients, both in the IPWT (HR = 0.61, p<0.0001) and the PSM cohort (HR = 0.55, p<0.0001). This difference disappeared when censoring ART modification for simplification, both in the IPWT (HR = 0.97, p = 0.65) and the PSM cohort (HR = 0.91, p = 0.33). A lower rate of virological failure was observed with STRs than with non-STRs in both cohorts (HR = 0.23; p = 0.002 and HR = 0.22, p = 0.003, respectively). A lower rate of treatment modification for adverse event was observed with non-STRs in the IPWT cohort (HR = 1.46, p<0.0001), but not in the PSM cohort (HR = 1.22, p = 0.11).ConclusionFirst-line therapy with STRs was associated with a longer time to treatment discontinuation than with non-STRs. However, when ART modification for simplification was not considered as a failure, STRs and non-STRs were similar.
| S-EPMC5289500 | biostudies-literature
Project description:BackgroundLiver diseases progress faster in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected persons than HIV-monoinfected persons. The aim of this study was to compare rates of liver fibrosis progression (measured by the aspartate-to-platelet ratio index [APRI]) among HIV-HCV-coinfected users of modern protease inhibitor (PI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens with a backbone of tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC).MethodsData from a Canadian multicenter cohort study were analyzed, including 315 HCV polymerase chain reaction-positive persons who initiated antiretroviral therapy with a PI or NNRTI and a backbone containing either TDF/FTC or ABC/3TC. Multivariate linear regression analyses with generalized estimating equations were performed after propensity score matching to balance covariates across classes of anchor agent.ResultsA backbone of TDF/FTC was received by 67% of PI users and 69% of NNRTI users. Both PI and NNRTI use was associated with increases in APRI over time when paired with a backbone of ABC/3TC: 16% per 5 years (95% confidence interval [CI], 4%, 29%) and 11% per 5 years (95% CI, 2%, 20%), respectively. With TDF/FTC use, no clear association was found among PI users (8% per 5 years, 95% CI, -3%, 19%) or NNRTI users (3% per 5 years, 95% CI, -7%, 12%).ConclusionsLiver fibrosis progression was more influenced by the backbone than by the class of anchor agent in HIV-HCV-coinfected persons. Only ABC/3TC-containing regimens were associated with an increase of APRI score over time, regardless of the class of anchor agent used.
| S-EPMC4690484 | biostudies-literature
Project description:ObjectivesData are lacking on the virologic efficacy and durability of modern antiretroviral treatment (ART) regimens during pregnancy. We compared virologic outcomes at delivery among women receiving dolutegravir versus other ART and the rate of change of the initial pregnancy regimen.DesignSingle-site retrospective cohort between 2009 and 2019.MethodsWe used univariable and multivariable generalized estimating equations to model the relationship between the maternal ART anchor and the proportion of women with a detectable viral load (greater than or equal to 20 HIV RNA copies/mL of plasma) closest to delivery (suboptimal virologic control) and with a detectable viral load at any time in the third trimester. We also compared changes in ART during pregnancy.ResultsWe evaluated 230 pregnancies in 173 mothers. Rates of optimal virologic control at delivery did not significantly differ in mothers who received dolutegravir (93.1%), rilpivirine (92.1%), boosted darunavir (82.6%), or efavirenz (76.9%) but were significantly lower among mothers receiving atazanavir (49.0%) or lopinavir (40.9%). The odds of having a detectable viral load at any time in the third trimester was also higher for atazanavir and lopinavir. Raltegravir, elvitegravir, or bictegravir were used in less than 10 mothers at delivery, which precluded statistical analyses. The frequency of change in ART was significantly higher in mothers who initially received elvitegravir (68%) or efavirenz (47%) than dolutegravir (18%).ConclusionDolutegravir-containing, rilpivirine-containing, and boosted darunavir-containing regimens conferred excellent virologic control in pregnancy. Atazanavir and lopinavir, elvitegravir, and efavirenz were associated with either high rates of virologic failure or regimen change during pregnancy.
| S-EPMC11375792 | biostudies-literature
Project description:OBJECTIVES:The integrase strand inhibitor dolutegravir (DTG) combined with tenofovir and lamivudine (TLD) is a single tablet regimen recommended for 1st, 2nd and 3rd-line public health antiretroviral therapy (ART). We determined drug resistance mutations (DRMs) and evaluated the predictive efficacy of a TLD containing regimen for viremic adolescents and young adults in Harare, Zimbabwe. METHODS:We sequenced plasma viral RNA from HIV-1-infected adolescents and young adults on 1st and 2nd-line ART with confirmed virologic failure (viral load >1000 copies/ml) and calculated total genotypic susceptibility scores to current 2nd, 3rd line and DTG regimens. RESULTS:A total of 160 participants were genotyped; 112 (70%) on 1st line and 48 (30%) on 2nd line, median (interquartile range) age 18 (15-19) and duration of ART (interquartile range) was 6 (4-8) years. Major DRMs were present in 94 and 67% of 1st and 2nd-line failures, respectively (P?<?0.001). Dual class resistance to nucleotide reverse transcriptase inhibitors and nonnucleotide reverse transcriptase inhibitors was detected in 96 (60%) of 1st-line failures; protease inhibitor DRMs were detected in a minority (10%) of 2nd-line failures. A total genotypic susceptibility score of 2 or less may risk protease inhibitor or DTG monotherapy in 11 and 42% of 1st-line failures switching to 2nd-line protease inhibitor and TLD respectively. CONCLUSION:Among adolescents and young adults, current protease inhibitor-based 2nd-line therapies are poorly tolerated, more expensive and adherence is poor. In 1st-line failure, implementation of TLD for many adolescents and young adults on long-term ART may require additional active drug(s). Drug resistance surveillance and susceptibility scores may inform strategies for the implementation of TLD.
| S-EPMC6668919 | biostudies-literature
Project description:Once-daily, single-tablet regimens have become integral to the management of human immunodeficiency virus type 1 infection, partly because they may improve adherence due to a lower pill burden. This article reviews the single-tablet options.
| S-EPMC4296592 | biostudies-other
Project description:IntroductionGuidelines advocate the treatment of HCV in all HIV/HCV co-infected individuals. The aim of this randomized, open-label study (ClinicalTrials.gov identifier: NCT02707601; https://clinicaltrials.gov/ct2/show/NCT02707601) was to evaluate the safety/efficacy of ledipasvir/sofosbuvir (LDV/SOF) co-administered with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or rilpivirine/F/TAF (R/F/TAF) in HIV-1/HCV co-infected participants.MethodsParticipants with HIV-1 RNA <50 copies/mL and chronic HCV-genotype (GT) 1 (HCV treatment-naïve ± compensated cirrhosis or HCV treatment-experienced non-cirrhotic) were randomized 1:1 to switch to E/C/F/TAF or R/F/TAF. If HIV suppression was maintained at Week 8, participants received 12 weeks of LDV/SOF. The primary endpoint was sustained HCV virologic response 12 weeks after LDV/SOF completion (SVR12).ResultsOf 150 participants, 148 received ≥1 dose of HIV study drug and 144 received LDV/SOF (72 in each F/TAF group; 83% GT1a, 94% HCV treatment-naïve, 12% cirrhotic). Overall, SVR12 was 97% (95% confidence interval: 93-99%). Black race did not affect SVR12. Of four participants not achieving SVR12, one had HCV relapse, one had HCV virologic non-response due to non-adherence, and two missed the post-HCV Week 12 visit. Of 148 participants, 96% receiving E/C/F/TAF and 95% receiving R/F/TAF maintained HIV suppression at Week 24; no HIV resistance was detected. No participant discontinued LDV/SOF or E/C/F/TAF due to adverse events; one participant discontinued R/F/TAF due to worsening of pre-existing hypercholesterolemia. Renal toxicity was not observed in either F/TAF regimen during LDV/SOF co-administration. In conclusion, high rates of HCV SVR12 and maintenance of HIV suppression were achieved with LDV/SOF and F/TAF-based regimens.ConclusionThis study supports LDV/SOF co-administered with an F/TAF-based regimen in HIV-1/HCV-GT1 co-infected patients.
| S-EPMC6988963 | biostudies-literature
Project description:IntroductionHigh levels of adherence to antiretroviral therapy (ART) are central to HIV management. The objective of this study was to compare multiple measures of adherence and investigate factors associated with adherence among HIV-infected children in western Kenya.MethodsWe evaluated ART adherence prospectively for six months among HIV-infected children aged ≤14 years attending a large outpatient HIV clinic in Kenya. Adherence was reported using caregiver report, plasma drug concentrations and Medication Event Monitoring Systems (MEMS®). Kappa statistics were used to compare adherence estimates with MEMS®. Logistic regression analyses were performed to assess the association between child, caregiver and household characteristics with dichotomized adherence (MEMS® adherence ≥90% vs. <90%) and MEMS® treatment interruptions of ≥48 hours. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.ResultsAmong 191 children, mean age at baseline was 8.2 years and 55% were female. Median adherence by MEMS® was 96.3% and improved over the course of follow-up (p<0.01), although 49.5% of children had at least one MEMS® treatment interruption of ≥48 hours. Adherence estimates were highest by caregiver report, and there was poor agreement between MEMS® and other adherence measures (Kappa statistics 0.04-0.37). In multivariable logistic regression, only caregiver-reported missed doses in the past 30 days (OR 1.25, 95% CI 1.14-1.39), late doses in the past seven days (OR 1.14, 95% CI 1.05-1.22) and caregiver-reported problems with getting the child to take ART (OR 1.10, 95% CI 1.01-1.20) were significantly associated with dichotomized MEMS® adherence. The caregivers reporting that ART made the child sick (OR 1.12, 95% CI 1.01-1.25) and reporting difficulties in the community that made giving ART more difficult (e.g. stigma) (OR 1.14, 95% CI 1.02-1.27) were significantly associated with MEMS® treatment interruptions in multivariable logistic regression.ConclusionsNon-adherence in the form of missed and late doses, treatment interruptions of more than 48 hours and sub-therapeutic drug levels were common in this cohort. Adherence varied significantly by adherence measure, suggesting that additional validation of adherence measures is needed. Few factors were consistently associated with non-adherence or treatment interruptions.
| S-EPMC4245448 | biostudies-literature
Project description:ObjectivesTo compare outcomes with single tablet regimens (STR) versus multi-tablet regimens (MTR) for human immunodeficiency virus (HIV) treatment using published data.DesignSystematic review and random-effects meta-analysis of literature on approved and investigational HIV regimens.MethodsThe research followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Single or un-blinded studies reporting a direct comparison between STR and MTR were eligible for the meta-analysis. Double-blinded studies were excluded due to lack of difference in pill burden between cohorts. The key outcomes of interest included: adherence rates/proportion meeting target, efficacy, safety/tolerability, non-clinical and economic outcomes.ResultsAfter screening 63 full-text articles and posters, 14 studies were eligible for the meta-analysis. The analysis showed that patients taking STR had improved outcomes over those taking MTR. Patients were significantly more adherent regardless of daily dosing frequency (odds ratio [OR]: 1.96, p < 0.001) and were more likely to achieve virological suppression (relative risk [RR]: 1.05, p = 0.002). There was a trend toward a lower discontinuation risk in the STR cohort, together with reported higher therapy satisfaction, better symptom control, improved health status, reduced healthcare resource utilization and demonstrated cost-effectiveness compared to MTR. There were no differences in CD4 cell count increase (at 48 weeks) or safety outcomes.ConclusionsThe findings of this study confirm previously reported preliminary findings of the advantages of STR over MTR for HIV treatment in adherence, therapy continuation, viral suppression, tolerability, quality of life improvement, cost-effectiveness and healthcare resource utilization.
| S-EPMC6206661 | biostudies-literature