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Aim: This study examined antiretroviral therapy (ART) persistence in treatment-experienced people with HIV (PWH) who switched or restarted guideline-recommended, integrase strand transfer inhibitor (INSTI)-based multi-tablet (MTR) and single tablet regimens (STR). Methods: Claims data from the Optum Research Database (01/01/2010-03/31/2020) was used to identify lines of therapy (LOTs) for treatment-experienced adults who switched or restarted INSTI-based regimens between 01/01/2018-12/31/2019, excluding drugs approved late in the study. LOT duration and reason for LOT cessation were compared for INSTI-based MTR vs. STR and among individual INSTI-based regimens. Adjusted hazard ratios (HR) were examined following propensity score weighting to control for differences. Results: In the sample, 3625 started STRs and 626 started MTRs including: bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (STR) (64.2%), dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) (STR) (21.1%), dolutegravir + emtricitabine/tenofovir alafenamide (DTG + FTC/TAF) (MTR) (12.7%) and dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG + FTC/TDF) (MTR) (2.1%). Discontinuation (11 vs. 15%, p = 0.003) and switching (7 vs. 25%, p < 0.001) were less common for STRs vs. MTRs. After adjusting, discontinuation and switching rates were higher for DTG/ABC/3TC, DTG + FTC/TAF and DTG + FTC/TDF compared with B/F/TAF. Conclusion: PWH treated with INSTI-based STRs discontinued or switched regimens less than those on MTRs. B/F/TAF was associated with less switching and discontinuation. Plain Language Summary People with HIV (PWH) can get their medicine in a single pill or in multiple different pills. This study examined patients who were already taking medication and were switching to or restarting different single-tablet or muti-tablet medication regimens. We used data from health insurance claims to see how long patients took their medication and whether they continued their medication and looked to see if there were differences between those who were taking STRs and MTRS. We also examined differences between specific regimens. We found that PWH treated with STRs discontinued or switched regimens less than those on MTRs. One specific regimen, bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), was also found to be associated with less switching and discontinuation. Background This study assesses persistence in treatment-experienced people with HIV (PWH) treated with different Department of Health and Human Services (DHHS) guideline recommended integrase strand transfer inhibitor (INSTI)-based single tablet regimens (STRs) or multi-tablet regimens (MTRs). Methods Insurance claims data from the Optum Research Database (01/01/2010-03/31/2020) was used to identify lines of therapy (LOTs) for treatment-experienced adults who switched or restarted INSTI-based regimens between 01/01/2018-12/31/2019. Among INSTI-based STRs and MTRs, LOT duration and reason for LOT cessation were compared. Differences between specific regimens were also compared. To adjust for differences between groups, adjusted hazard ratios (HR) from Cox proportional hazard models were examined. Results We found that rates of discontinuation (11 vs. 15%, p = 0.003) and switching (7 vs. 25%, p < 0.001) were both less frequent for STRs when compared with MTRs. After adjusting, we found that both discontinuation and switching rates were higher for the regimens dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) (STR) and dolutegravir + emtricitabine/tenofovir alafenamide (DTG + FTC/TAF) and dolutegravir + emtricitabine/tenofovir disoproxil fumarate DTG + FTC/TDF (both MTRs) compared with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). Discussion Among treatment experienced PWH treated with INSTI-based regimens, those treated with STRs discontinued or switched regimens less than those on MTRs. Compared with other regimens (both STRS and MTRs) B/F/TAF was associated with less switching and discontinuation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Two-drug regimens antiretroviral therapies are increasingly prescribed to HIV patients, as they are recommended by international guidelines, and they show an excellent efficacy, safety, and tolerability profile. Regimens administered as single tablets (STRs) are usually preferred by patients and they are associated with higher adherence. CASE REPORT: We report two cases of drug-induced hypersensitivity (DIH) that occurred after switching from dolutegravir (DTG) plus rilpivirine (RPV) in separate pills to a fixed dose combination containing the same molecules (DTG/RPV; Juluca®). Following the DIH event, DTG/RPV coformulation was discontinued. At symptomatic resolution, they continued to receive DTG plus RPV in separate pills uneventfully. The component present only in the DTG/RPV coformulation was iron oxide red (E172), contained in the film-coating. Iron oxide red is an approved colorant, used as drug excipient. Patch test with DTG/RV coformulation performed several months after the DIH event was negative. Drug allergy to excipients remains underappreciated and underreported and frequently leads to inappropriate medication discontinuation. CONCLUSION: Our case underscores the role of meticulous medication allergy history in differentiating true medication allergy from excipient allergy. This observation may be useful in the era of antiretroviral simplification to two-drug regimens. [ABSTRACT FROM AUTHOR]

Hung-Chin Tsai,1– 5 I-Tzu Chen,1 Hui-Min Chang,6– 8 Susan Shin-Jung Lee,1,2 Yao-Shen Chen1,2 1Division of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 3Department of Parasitology, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan; 6Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 7Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 8Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung, TaiwanCorrespondence: Hung-Chin Tsai, Division of Infectious Diseases, Department of Medicine Kaohsiung Veterans General Hospital, #386 Ta-Chung 1st Road, Kaohsiung, 813, Taiwan, Tel +886 7 3422121 ext. 2029, Fax +886 7 346 8292, Email hctsai1011@yahoo.com.tw; tsaihungchin@gmail.comPurpose: This study aimed to investigate the prevalence of resistance to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based single-tablet regimen (STR) in Taiwanese patients and clarify the clinical implications of using doravirine in patients who fail NNRTI treatment.Patients and Methods: Taiwanese patients infected with HIV-1 who failed NNRTI-based STR treatment were enrolled in this retrospective cohort study from 2015 to 2020. Mutations associated with drug resistance were identified using the 2019 International Antiviral Society-USA list of drug-resistant mutations in HIV, and drug susceptibility was assessed according to the Stanford HIV Drug Resistance Database version 9. Median values of continuous variables were compared between two groups using the Mann–Whitney U-test, and categorical variables were compared using the chi-square test or Fisher’s exact test.Results: A total of 107 patients were included, of whom 29 were treatment failure to the initial STRs, and 78 failed treatment after switching to an STR. Seventy-four patients failed treatment with TDF/FTC/EFV (Atripla), 30 with TDF/FTC/RPV (Complera) and 3 with TAF/FTC/RPV (Odefsey). The prevalence rates of resistance to nucleoside reverse transcriptase inhibitors (NRTIs), NNRTIs, protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) were 76%, 86%, 3% and 2%, respectively. Among the 29 patients failure to the initial STRs, 62% developed doravirine resistance, compared to 64% of the 78 the patients who failed treatment after switching to an STR. There were no significant differences in the prevalence of specific NNRTI or doravirine resistance-associated mutations between these two groups. The patients with K65R mutations were more likely to have NNRTI resistance (p = 0.037) and doravirine resistance (p < 0.001).Conclusion: Our findings showed a high rate of doravirine cross-resistance in patients with NNRTI-based STR treatment failure. Doravirine should be used cautiously as a salvage regimen in patients who fail NNRTI treatment.Keywords: HIV, doravirine, drug resistance, single-tablet regimen, virological failure

Background: Many people living with HIV struggle to consistently adhere to antiretroviral therapy, fail to achieve long-term virologic control and remain at risk for HIV-related disease progression, development of resistance and may transmit HIV infection to others. Objective: To determine if switching from current multi-tablet (curART) to single-tablet antiretroviral therapy (abacavir/lamivudine/dolutegravir; ABC/3TC/DTG), both combined with individualized adherence support, would improve HIV suppression in non-adherent vulnerable populations. Methods: TriiADD was an investigator-initiated randomized, multicentre, open label study. HIV+ adults with documented non-adherence on curART were randomized in a 1:1 ratio to immediately switch to ABC/3TC/DTG or to continue curART. Both arms received adherence support. The primary outcome was the proportion of participants in each arm with HIV RNA < 50 copies/mL 24 weeks after randomization. Results: In total, 50 people were screened and 27 randomized from 11 sites across Canada before the trial was stopped early due to slow recruitment. Participants were predominantly from ethnocultural communities, Indigenous people and/or had a history of injection drug use. The proportion achieving HIV RNA < 50 copies/mL at week 24 was 4/12 (33%) in the curART arm vs 7/13 (54%) in the ABC/3TC/DTG arm; median Bayesian risk difference, 5% (95% CrI, − 17 to 28%) higher for those randomized to ABC/3TC/DTG. We encountered difficulties with recruitment of participants without prior drug resistance, retention despite intensive support, reliably measuring adherence and in overcoming entrenched adherence barriers. Conclusion: Results of our trial are consistent with a slight improvement in viral suppression in a vulnerable population when a single tablet regimen is combined with patient-level adherence support. Beyond treatment simplicity and tolerability, tailored interventions addressing stigma and social determinants of health are still needed. The numerous challenges we encountered illustrate how randomised trials may not be the best approach for assessing adherence interventions in vulnerable populations. [ABSTRACT FROM AUTHOR]

Abstract Background A single-tablet regimen (STR) has been associated with better drug adherence. However, the durability of different STRs was unknown in the real-world settings. Our aim was to investigate the durability of different initial STR regimens in antiretroviral-naive patients starting STR in southern Taiwan. Method This was a retrospective study of antiretroviral-naive patients that initiated first-line antiretroviral regimens with STRs between May 2016 and December 2017. The primary endpoint was time to virological failure. Secondary endpoints were STR discontinuation due to toxicity/intolerance. Durability was defined as time from the initiation until discontinuation/modification. Kaplan- Meier curves were plotted assessing time to virological suppression, treatment failure and discontinuation for the three STRs and Cox proportional hazards model was used to analyze the factors associated with time to viral suppression, treatment failure or discontinuation. Results Two hundred and twenty-three patients were included: The median follow-up duration (IQR) was 73.9 (48–101.6) weeks, 25 patients (11%) experienced virological failure; the 48 weeks probability of treatment failure was 22.9% (16/70) for Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF), 24.1% (13/54) for Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (FTC/RPV/TDF) and 24.2% (24/99) for Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC) (p=0.16). Fifty-six patients (25%) discontinued their STRs owing to toxicity/intolerance. When compared to EFV/FTC/TDF, treatment with FTC/RPV/TDF (aHR 8.39, CI 1.98–35.58, p = 0.004) and ABC/DTG/3TC (aHR 8.40, CI 2.39–29.54, p=0.001) were more likely to have treatment failure. The predictors for treatment failure included age ≦ 30 years old (aHR 3.73, CI 1.25–11.17, p = 0.018), switch between different STR (aHR 2.3, CI 1.18–4.50, p = 0.001) and free of active syphilis infection (aHR 0.24, CI 0.08–0.73, p = 0.012). The risk factor for treatment discontinuation included younger age ≦ 30 years old (aHR 3.82, CI 1.21–12.37, p = 0.023), treatment with EFV/FTC/TDF (aHR 8.65, CI 2.64–28.39, p

Data on the long-term durability of rilpivirine (RPV) are still scarce. A two-center retrospective study was performed, including all people living with HIV (PLWH) treated with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)/RPV or tenofovir alafenamide (TAF)/FTC/RPV in the period January 2013–December 2019. Aims of the study were to assess the rate of discontinuation of the RPV single-tablet regimen (STR) and identify factors associated with the risk of discontinuation according to Cox's regression analysis. A total of 684 PLWH were enrolled. Mean duration of RPV-STR treatment was 192.5 (±99.5) weeks for 123 antiretroviral therapy (ART)-naïve participants (18%) and 173.3 (± 85.6) weeks for 561 ART-experienced study participants (82%). During the study period, the incidence of discontinuation was 7.7 per 100 person-years. The estimated proportions of discontinuation after 48 and 96 weeks were 5.6% and 13.4%, respectively. Causes of discontinuation were loss to follow-up (30%), side effects (15%), ART optimization (14%), virological failure (VF) (12%), death or transfer to another center (9%), low adherence (7%), drug interactions (6%), simplification to dual therapy (3%), and unknown (3%). No differences were observed in cumulative probability of discontinuation between ART-naïve and -experienced PLWH. Heterosexual (hazard ratio [HR] 3.0, 95% confidence interval [CI] 1.4–6.8) and mother-to-child (HR 5.3, 95% CI 1.8–15.3) transmission of HIV infection and history of previous VF (HR 1.7, 95% CI 1.2–2.5) were associated with higher risk of discontinuation. High RPV-STR effectiveness and durability were confirmed in our real-life population of PLWH. Given these data, RPV has the potential to be a drug for life in patients selected according to current guidelines. [ABSTRACT FROM AUTHOR]

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.

Background: A single-tablet regimen (STR) has been associated with better drug adherence. However, the durability of different STRs was unknown in the real-world settings. Our aim was to investigate the durability of different initial STR regimens in antiretroviral-naive patients starting STR in southern Taiwan.Method: This was a retrospective study of antiretroviral-naive patients that initiated first-line antiretroviral regimens with STRs between May 2016 and December 2017. The primary endpoint was time to virological failure. Secondary endpoints were STR discontinuation due to toxicity/intolerance. Durability was defined as time from the initiation until discontinuation/modification. Kaplan- Meier curves were plotted assessing time to virological suppression, treatment failure and discontinuation for the three STRs and Cox proportional hazards model was used to analyze the factors associated with time to viral suppression, treatment failure or discontinuation.Results: Two hundred and twenty-three patients were included: The median follow-up duration (IQR) was 73.9 (48-101.6) weeks, 25 patients (11%) experienced virological failure; the 48 weeks probability of treatment failure was 22.9% (16/70) for Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF), 24.1% (13/54) for Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (FTC/RPV/TDF) and 24.2% (24/99) for Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC) (p=0.16). Fifty-six patients (25%) discontinued their STRs owing to toxicity/intolerance. When compared to EFV/FTC/TDF, treatment with FTC/RPV/TDF (aHR 8.39, CI 1.98-35.58, p = 0.004) and ABC/DTG/3TC (aHR 8.40, CI 2.39-29.54, p=0.001) were more likely to have treatment failure. The predictors for treatment failure included age ≦ 30 years old (aHR 3.73, CI 1.25-11.17, p = 0.018), switch between different STR (aHR 2.3, CI 1.18-4.50, p  = 0.001) and free of active syphilis infection (aHR 0.24, CI 0.08-0.73, p = 0.012). The risk factor for treatment discontinuation included younger age ≦ 30 years old (aHR 3.82, CI 1.21-12.37, p = 0.023), treatment with EFV/FTC/TDF (aHR 8.65, CI 2.64-28.39, p < 0.001) and free of active syphilis infection (aHR 0.16, CI 0.04-0.62, p = 0.006).Conclusion: Younger age was associated with treatment failure and drug discontinuation. Active syphilis infection s/p treatment was associated with free from treatment failure and discontinuation. This probably driven by the more frequently sexual health education and counseling when patients had syphilis infection. Treatment with ABC/DTG/3TC was associated with higher risk of treatment failure. The STR durability was dependent on the drug toxicity/intolerance, age and syphilis infection. [ABSTRACT FROM AUTHOR]

Single tablet regimens (STRs) have simplified antiretroviral therapy (ART) over the years in the adult human immunodeficiency virus (HIV) population. However, there is still a prevalent need to simplify regimens in children and adolescents living with HIV. Finding the optimal regimen requires a multi-factorial approach due to their complex pharmacokinetic profiles throughout childhood and the challenges and limitations of medication non-adherence in the pediatric population. These challenges include pill size, available formulations, palatability, and caregiver health literacy, which can all affect the proper administration of medications. The complexity of this population implies the importance of customizing everyone's antiretroviral regimen so that the patient and family can successfully adhere to the therapy. The current recommendations for ART in the adult and pediatric populations are similar, yet the use of STRs are limited. The goal of this review was to assess current data on available STRs and determine their utility as ART in the pediatric population. ABBREVIATIONS 2DR, 2-drug regimen; 3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; ARV, antiretroviral; AUC, area under the curve; AUCtau, area under the plasma concentration versus time curve over the dosing interval; BIC, bictegravir; BMD, bone mineral density; CDC, Centers for Disease Control and Prevention; CNS, central nervous system; COBI, cobicistat; DHHS, Department of Health and Human Services; DRV, darunavir; DTG, dolutegravir; EFV, efavirenz; eGFR, estimated glomerular filtration rate; EVG, elvitegravir; FDA, US Food and Drug Administration; FDC, fixed-dose combination; FTC, emtricitabine; HIV, human immunodeficiency virus; INSTI, integrase strand transfer inhibitor; LPV/r, lopinavir/ritonavir; NRTI, nucleoside reverse transcriptase inhibitor; RPV, rilpivirine; SMR, sexual maturity rating; STR, single tablet regimen; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate, VL, viral load. [ABSTRACT FROM AUTHOR]

In Italy a proportion of HIV patients exceeding 50% are diagnosed at advanced stages of disease. A sizeable proportion of patients under chronic HIV treatment has a story of poor adherence with archived resistance associated mutations, a condition implying some risks in case of treatment with dual regimens. Conventional three-drug regimens will remain necessary in the short-mid term, in order to avoid treatment failure and selection of drug resistance. Efficacy, tolerability, safety, genetic barrier, forgiveness and a good compatibility with concurrent medications are all features that describe the overall quality of BIC/FTC/TAF, a combination whose robustness will remain a point of reference for the next years., Competing Interests: Conflict of interest None to declare.

Objectives: Treatment guidelines recommend single‐tablet regimens for patients with HIV infection starting antiretroviral therapy. These regimens might be as effective and cost less if taken as separate drugs. We assessed whether the one pill once a day combination of efavirenz, emtricitabine and tenofovir reduces the risk of disease progression compared with multiple‐pill formulations of the same regimen. Methods: We selected treatment‐naïve patients starting one‐, two‐ or three‐pill formulations of this regimen in data from the Antiretroviral Therapy Cohort Collaboration. These patients were followed until an AIDS event or death or until they modified their regimen. We analysed these data using Cox regression models, then used our models to predict the potential consequences of exposing a future population to either a one‐pill regimen or a three‐pill regimen. Results: Among 11 739 treatment‐naïve patients starting the regimen, there were 386 AIDS events and 87 deaths. Follow‐up often ended when patients switched to the same regimen with fewer pills. After the first month, two pills rather than one was associated with an increase in the risk of AIDS or death [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.01‐1.91], but three pills rather than two did not appreciably add to that increase (HR 1.19; 95% CI 0.84‐1.68). We estimate that 77 patients would need to be exposed to a one‐pill regimen rather than a three‐pill regimen for 1 year to avoid one additional AIDS event or death. Conclusions: This particular single‐tablet regimen is associated with a modest decrease in the risk of AIDS or death relative to multiple‐pill formulations. [ABSTRACT FROM AUTHOR]

Several antiretrovirals (ART) have been coformulated as single tablet regimens (STR). Study objectives were to compare ART and non-ART adherence between STR and multiple tablet regimens (MTR) recipients, determine whether STR independently predicts ART adherence, and determine whether ART adherence influences non-ART adherence. A retrospective cohort study was performed among Upstate New York Veterans' Healthcare Administration (VISN-2) patients from 2000 to 2013. Inclusion criteria were age ≥18 years, human immunodeficiency virus (HIV) infection, receipt of ≥3 ART medications for ≥3 months, and available pharmacy refill records. The two study outcomes were adherence to ART medications and non-ART medications. Adherence was determined with pharmacy refill records that were used to calculate medication possession ratios. Among the 1202 subjects, there were 165 (13.7%) STR and 1037 (86.3%) MTR recipients. Mean ± standard deviation (SD) ART adherence was significantly higher for STR recipients (81.5% ± 15.3%) than MTR recipients (66.1% ± 21.1%), p < 0.001. Use of STR [adjusted odds ratio (aOR): 5.76, 95% confidence interval (CI): 3.84-8.65, p < 0.001] was independently associated with optimal (≥90%) adherence to ART. Mean ± SD non-ART adherence did not differ between STR (78.8% ± 15.6%) and MTR recipients (80.8% ± 16.0%), p = 0.17. Optimal adherence to ART medications (aOR: 2.30, 95% CI: 1.57-3.38, p < 0.001) was independently associated with optimal adherence to non-ART medications. The use of STRs are associated with optimal adherence to ART medications, but not directly associated with adherence to non-ART medications. [ABSTRACT FROM AUTHOR]

Introduction High adherence and satisfaction with HIV therapy may positively influence retention on HIV treatment and therapeutic outcomes. Simplification of treatment with once-daily single tablet regimens (STRs) can increase treatment acceptability. Aim We evaluated adherence, patient's satisfaction with HIV therapy and perception of their own state of health according to type of combined antiretroviral therapy (cART): STR or non-STR (more than one pill/day or BID). Material and methods We interviewed 80 patients across Poland; 57 responded and completed a semi-structured anonymous questionnaire designed to evaluate their attitudes towards cART. The questionnaire was developed originally in Italy by Gilead Sciences in cooperation with GfK Italy (Society for Consumer Research) and Fondazione NADIR Onlus. The basis of the survey was the AIDS Clinical Trial Group questionnaire complemented by a visual analogue scale and questions about satisfaction with treatment and overall health based on their own self-assessment. Results Most of the subjects were males (77%) with a mean age of 44 years, with secondary school education level (51%) and a long history of HIV infection (mean 12.3 years). STRs were taken by 26% patients, among them 53% were taking FTC/TDF/RPV. Overall, 72% of patients are satisfied with their current treatment. More patients taking an STR were very satisfied or satisfied with their HIV therapy than patients taking more complicated regimens (94% vs. 64%, respectively; p=0.0257). About 60% of respondents considered their overall health as excellent, very good or good. A significant difference between the groups in this aspect was observed: 53% of patients on a STR rated it as excellent or very good, while in the group not on a STR this was only 28% (p=0.0462). It has been shown that 65% of patients did not miss any dose and additional 18% took 90% of prescribed drugs in the last 30 days prior to testing. Conclusion Overall 72% of patients were satisfied with their current treatment. Single tablet regimens were associated with higher treatment satisfaction and better self-perceived state of health compared to more complex regimens. Based on the results obtained from the analysis of the visual analogue scale, adherence can be considered as relatively high (83% of patients took 90-100% of their drugs) in this surveyed population of Polish patients. [ABSTRACT FROM AUTHOR]

Single tablet combination of tenofovir disoproxil fumarate, emtricitabine, elvitegravir and cobicistat [TDF/FTC/EVG/COBI] has been licensed for the use in HIV infected individuals as Stribild ® . In treatment naïve subjects high virological efficacy of the regimen was proved. Recently use of this combination has been investigated as the switch option for the virologically suppressed individuals without drug resistance to the components of the compound. In twin studies – STRATEGY-NNRTI and STRATEGY-PI non-inferiority of the switch to TDF/FTC/EVG/COBI was confirmed, discontinuations due to adverse events were infrequent and no emergence of integrase drug resistance was observed. Simplification of the treatment using Stribild is an attractive, effective, safe and well tolerated option which also allows for the optimization of adherence. Elvitegravir-based therapies may be used to replace other antiretroviral regimens in virologically suppressed cases, with no compromise to the virological efficacy of the combination. Use of this novel integrase inhibitor seems to provide durable option for the long-term treatment. In this review we also present a case of the successful treatment optimization with TDF/FTC/EVG/COBI in a patient with poor adherence and protease resistance. [ABSTRACT FROM AUTHOR]

Objectives Emtricitabine/tenofovir/rilpivirine as a single-tablet regimen ( STR) is widely used without licence in treatment-experienced patients. The purpose of this retrospective observational study was to assess viral suppression of ART-experienced patients switching to STR. Methods We assessed 131 pretreated patients switching to STR with HIV RNA < 400 HIV-1 RNA copies/mL. The primary outcome measure was the proportion of patients at week 24 with HIV RNA < 40 copies/mL. Results By week 24, eight patients had stopped STR: four because of adverse events and four for other reasons. Three virological failures were observed; among these, at least one patient developed cross-resistance to nucleoside reverse transcriptase inhibitors ( NRTIs) and nonnucleoside reverse transcriptase inhibitors ( NNRTIs), in particular with the E138K pattern. In intent-to-treat analysis, 92% of participants (120 of 131) achieved HIV RNA < 40 copies/mL. Only grade 1 to 2 adverse events were observed, mainly consisting of increased liver enzymes (n = 33). Systemic exposure to rilpivirine was above the usually observed steady-state levels for the 18 measurements assessed. Conclusions Efficacy and tolerability are similar to those in treatment-naïve patients. [ABSTRACT FROM AUTHOR]

Objectives Whether treatment-experienced HIV-1-infected patients with an acquired K103N mutation after failing nonnucleoside reverse transcriptase inhibitor ( NNRTI) regimens can be treated with rilpivirine is unknown. The aim of this pilot study was to evaluate the efficacy of rilpivirine/tenofovir/emtricitabine in HIV-1-infected patients with an isolated K103N mutation. Methods A prospective study was carried out in HIV-1-infected adults who acquired the K103N mutation on failing NNRTI regimens. No other mutations in reverse transcriptase were allowed. Patients had to be on second-line regimens with HIV-1 RNA < 200 copies/mL for ≥ 6 months. Exclusion criteria were: use of acid-reducing agents, insufficient caloric intake and impaired renal function. Of primary interest was virological success ( HIV-1 RNA < 200 copies/mL) at weeks 6, 12, 24 and 48. Results Of 1550 HIV-1-infected patients at the Erasmus Medical Center Rotterdam, we identified 10 HIV-1-infected patients with an isolated K103N mutation acquired after NNRTI failure. Five patients were not eligible for inclusion in the study, and two patients refused participation. Three African women (23-35 years of age) were included and were switched from boosted protease inhibitor-based second-line therapies to rilpvirine/tenofovir/emtricitabine. HIV-1 RNA was < 200 copies/mL at weeks 6, 12, 24 and 48 for all patients. No adverse events were observed. All patients had HIV-1 RNA < 200 copies/mL for 6−50 months prior to the switch. Conclusions This pilot study demonstrates the successful switch of HIV-1-infected patients who acquired an isolated K103N mutation during previous NNRTI therapy to rilpivirine/tenofovir/emtricitabine. In selected patients, single-tablet regimens are also becoming a valid treatment option for second-line HIV-1 therapy. [ABSTRACT FROM AUTHOR]

Abstract: Efforts to address HIV infection have been highly successful, enabling chronic suppression of viral replication with once-daily regimens. More recent research into HCV therapeutics have also resulted in very promising clinical candidates. This Digest explores similarities and differences in the two fields and compares the chronology of drug discovery relative to the availability of enabling tools, and concludes that safe and convenient, once-daily regimens are likely to reach approval much more rapidly for HCV than was the case for HIV. [Copyright &y& Elsevier]

Objective: To analyze self-reported adherence to antiretroviral regimens containing ritonavir-boosted protease inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTI), raltegravir, and maraviroc. Methods: Overall, 372 consecutive subjects attending a reference center for HIV treatment in Florence, Italy, were enrolled in the study, from December 2010 to January 2012 (mean age 48 years). A self-report questionnaire was filled in. Patients were defined as "nonadherent" if reporting one of the following criteria: ,90% of pills taken in the last month, $1 missed dose in the last week, spontaneous treatment interruptions reported, or refill problems in the last 3 months. Gender, age, CD4, HIV-RNA, years of therapy, and type of antiretroviral regimen were analyzed with respect to adherence. Results: At the time of the questionnaire, 89.8% of patients had ,50 copies/mL HIV-RNA and 14.2% were on their first combined antiretroviral therapy. 57% of patients were prescribed a regimen containing ritonavir boosted protease inhibitors (boosted PI), 41.7% NNRTI, 17.2% raltegravir, and 4.8% maraviroc; 49.5% of the subjects were on bis-in-die regimens, while 50.5% were on OD regimens, with 23.1% of these on the single tablet regimen (STR): tenofovir/emtricitabine/efavirenz. The nonadherence proportion was lower in NNRTI than in boosted-PI treatments (19.4% vs 30.2%), and even lower in STR patients (17.4%). In multivariable logistic regression, patients with the NNRTI regimen (OR: 0.56, 95% CI: 0.34-0.94) and the STR (OR: 0.45, 95% CI: 0.22-0.92) reported lower nonadherence. Efavirenz regimens were also associated with lower nonadherence (OR: 0.42, 95% CI: 0.21-0.83), while atazanavir/ritonavir regimens were associated with higher nonadherence. No other relation to specific antiretroviral drugs was found. A higher CD4 count, lower HIV-RNA, and older age were also found to be associated with lower nonadherence, while a longer time on combined antiretroviral therapy was related to higher nonadherence. Conclusion: STR maintains an advantage in improving adherence with respect to other combined antiretroviral therapies, even though new antiretroviral drugs and drug classes have become available in recent years. [ABSTRACT FROM AUTHOR]