Two-drug Antiretroviral Regimens Research Articles

Cytokines assets in PLWH in two-drug dolutergravir based or three-drug antiretroviral regimen

To minimize the toxicity and impact of combined antiretroviral therapy (cART) on the lifestyle of people living with Human Immunodeficiency Virus (PLWH), scientific community evaluated the efficacy, safety and sustained virologic response of two drugs antiretroviral regimens, in particular dolutegravir (DTG). The effects of deintensification therapy on inflammatory settings are currently unknown in PLWH. Thus, our study explored the inflammatory state in virologically suppressed HIV individuals between patients in treatment with a DTG-containing dual therapy (2DR) versus triple regimen therapies (3DR). We enrolled a total of 116 subjects in 2DRs or 3DRs regimens, and the plasma levels of pro- and anti-inflammatory cytokines (in particular IL-1β, IL-10, IL-18, IL-33, IL-36 and IFN-γ) have been evaluated. CD4 + cell’s median value was 729.0 cell/µL in the 3DR group and 771.5 cell/µL in 2DR group; the viral load was negative in all patients. Significant differences were found in levels of IL-18 (648.8 cell/µL in 3DR group vs. 475.0 cell/µL in 2DR group, p = 0.034) and IL-36 (281.7 cell/µL in 3DR group vs. 247.0 cell/µL in 2DR group, p = 0.050), and a correlation between IL-18 and IL-36 was found in 3DR group (rho = 0.266, p = 0.015). This single-center retrospective pharmacological study confirms the absence of significant differences in IL-1β, IL-10, IL-33, and IFN-γ levels between patients on two-drug antiretroviral regimens compared to patients on 3DR antiretroviral regimens. Patients in 2DR show greater control over IL-18 and IL-36 serum levels, cytokines related to an increased cardiovascular risk and development of age-related chronic diseases. Based on our results, we suggest that DTG-based 2DR antiretroviral regimens could be associated with better control of the chronic inflammation that characterizes the population living with HIV in effective ART.

Response to Commentary: Long-term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens.

Response to Commentary: Long-term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens.

Commentary: Long-Term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens.

Commentary: Long-Term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens.

Long-Term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens.

BackgroundBecause inflammation is associated with mortality and has been linked to HIV transcription in lymphoid tissues during ART, it is necessary to address the long-term effects of switching 3-drug (3DR) to 2-drug regimens (2DR) on inflammation.MethodsNested study in the Spanish AIDS Research Network. We selected PWH ART-naive initiating 3DR who achieved viral suppression in the first 48 weeks and either remained on 3DR or switched to 2DR (3TC+bPI; 3TC+DTG; DTG+RPV). We assessed the trajectories on inflammatory markers during ART using multivariate piecewise mixed models.ResultsWe analyzed 619 plasma samples from 148 patients (3DR, N=90; 2DR, N=58), the median follow-up was 4.6 (IQR 3.2-6.2) years. There were no significant differences in baseline characteristics between groups. After adjusting for potential confounders, patients with 3DR experienced a slow decline of IL6, hs-CRP, sCD14, sCD163, and D-dimer over time. In contrast, compared to 3DR, switching to 2DR was associated with increases in IL-6 (p=0.001), hs-CRP (p=0.003), and D-dimer (p=0.001) after year 3 from virologic suppression. 2DR was associated with a higher risk of hs-CRP quartile increase (aOR 3.3, 95%CI 1.1-10) and D-dimer quartile increase (aOR 3.7, 95%CI 1.1-13). The adjusted biomarker trajectories did not reveal a distinct pattern according to the type of 2DR used (bPI vs DTG).ConclusionsIn this study in virally suppressed individuals, maintaining 3DR was associated with a more favorable long-term inflammatory profile than switching to 2DR. The potential clinical implications of these findings on the development of non-AIDS events deserve further investigation.

Uptake Success and Cost Savings from Switching to a Two-Drug Antiretroviral Regimen.

The emergence of dual therapy for antiretroviral (ARV)-experienced persons living with HIV (PWH) offers the opportunity to reduce lifetime exposure to unnecessary ARV drugs while maintaining viral suppression and reducing the cost of care. Our objective, using retrospective analysis of a quality care initiative, was to examine in routine clinical practice the clinical impact of switching PWH stable on a three-drug to a two-drug single-tablet formulation (STF) ARV regimen. We also examined the cost implications of this STF adjustment. Between January 1, 2020 and January 1, 2021 eligible patients (i.e., virally suppressed, no active hepatitis B infection, no documented nucleoside reverse transcriptase inhibitors/integrase strand transfer inhibitor resistance) were offered, on a convenience basis and as part of routine care, the opportunity to adjust their current three-drug STF to a two-drug STF (dolutegarvair/lamivudine). The acceptance, clinical efficacy, safety, tolerability, and cost of treatment were measured for patients who switched in 2020. Of 989 eligible PWH, 408 were approached and 391 (39.5%) switched to two-drug regimen; 99% remained on the two-drug STF at year's end (median 240 days follow-up). Only 2/391 patients who switched lost viral control. The total ARV drug cost for all 989 patients decreased by 10.3% generating an actual savings of $1,596,666 among patients approached and switched in 2020. Patient interest and uptake in switching to two-drug STF was substantial and resulted in few discontinuations for any reason. It provided significant and immediate cost savings within the first year. Our results bring clarity to discussions on whether using two-drug regimens would be practical and acceptable in nonclinical trial settings.

A Retrospective Analysis of Long-Term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens

A Retrospective Analysis of Long-Term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens

Two's a Company, Three's a Crowd: A Review of Initiating or Switching to a Two-Drug Antiretroviral Regimen in Treatment-Naïve and Treatment-Experienced Patients Living with HIV-1.

IntroductionAs HIV has become a manageable chronic condition, a renewed and increased interest in challenging traditional three-drug HIV therapies and moving toward two-drug regimens (2DR) for initial or maintenance treatment in people living with HIV (PLWH) has developed. As PLWH are living longer, continual advancements in antiretroviral regimens have been a focus to provide optimal life-long therapy options. Although early studies may have shown poor outcomes in virologic suppression with 2DR, newer studies and treatment options have emerged to show promise in the management of HIV. The purpose of this review is to evaluate current literature and assess the efficacy of two-drug (2DR) antiretroviral therapy in treatment-naïve and -experienced people living with HIV.MethodsA systematic search was performed between January 2009 to January 2020, using EMBASE, MEDLINE, Google Scholar, and bibliographies. Combinations of the following search terms were used: HIV-1 infection, antiretroviral therapy, dual therapy, two-drug regimen, two-drug therapy, two-drug regimen, and 2DR. Included studies were those in the adult population with at least one active comparator, outcomes assessing HIV-1 RNA viral load while on treatment, and written in English.ResultsThirty-three studies were included, 13 where 2DRs were evaluated as initial therapy (3 studies with extension data) and 15 where 2DRs were evaluated as maintenance or switch therapy (2 studies with extension data).ConclusionAlthough 2DRs may not be appropriate in all patient populations, they are being utilized more frequently and have the potential to reduce costs, adverse effects, and drug interactions.

Two-drug antiretroviral regimens: an assessment of virologic response and durability among treatment-experienced persons living with HIV in the OPERA® Observational Database.

IntroductionTwo‐drug regimens (2‐DR) have the potential to be a viable solution to the challenges of treatment complexity, cost, adverse effects and contraindications. We sought to describe the real‐world use and effectiveness of 2‐DR among persons living with HIV (PLHIV) in the United States.MethodsWe analysed data for 10,190 treatment‐experienced patients from the OPERA® Observational Database initiating a new 2‐DR or three‐drug regimen (3‐DR) between 1 January 2010 and 30 June 2016. Multivariate Cox Proportional Hazards models were used to estimate the association among 2‐DR or 3‐DR initiation and virologic suppression (viral load (VL) <50 copies/mL), virologic failure (2 VLs > 200 copies/mL or 1 VL > 200 copies/mL + discontinuation) or regimen discontinuation.ResultsPatients initiating a 2‐DR (n = 1337, 13%) were older, and more likely to have a lower CD4 count, a history of AIDS and comorbid conditions than patients initiating a 3‐DR. There was no difference between groups in time to virologic suppression (aHR: 1.00 (95% CI: 0.88, 1.13)) among viraemic patients (baseline VL ≥ 50 copies/mL, n = 4180), or time to virologic failure (aHR: 1.15 (95% CI: 0.90, 1.48)) among virologically stable patients (baseline VL < 50 copies/mL, n = 6010). However, time to discontinuation was shorter following 2‐DR than 3‐DR initiation (aHR: 1.51 (95% CI: 1.41, 1.61)).ConclusionsIn this large cohort of treatment‐experienced patients, 2‐DR prescriptions were common and more frequent among patients with significant comorbidity. Virologic response was similar, but duration of use was shorter with a 2‐DR than a 3‐DR, suggesting that 2‐DRs may be a virologically effective treatment strategy for treatment‐experienced PLHIV with existing comorbidities.

Simplifying ARV Therapy in the Setting of Resistance.

HIV treatment simplification is typically indicated for virologically suppressed patients with no baseline resistance-associated mutations (RAMs) or prior virologic failure (VF) to the simplification regimen. Simplification can occur to minimize pill burden, toxicities, drug-drug interactions, or costs. As most studies for treatment simplification excluded patients with baseline RAMs or prior VF, this review is aimed to critically analyze data regarding treatment simplification in treatment-experienced patients. Antiretroviral (ARV) regimens containing three-, two-, and one-drug(s) have been scarcely studied to assess virologic efficacy in treatment-experienced patients. Three-drug regimens with the most data and highest efficacy are with integrase strand transfer inhibitors (INSTIs). Regimens including dolutegravir (DTG) and bictegravir have been shown to maintain efficacy in patients with certain baseline RAMs. Dual therapy regimens include the use of DTG plus either lamivudine (3TC), rilpivirine (RPV), or other ARVs. None of these studies evaluated patients with baseline DTG resistance. Baseline RAMs to 3TC were not a predictor of VF in patients on DTG/3TC. Efficacy was seen with DTG/RPV; however, studies showed high rates of discontinuation. DTG plus boosted-protease inhibitors were studied in smaller but promising studies. Two small studies assessed the use of monotherapy with boosted darunavir or DTG, both showing virologic efficacy. Currently, three- and two-drug ARV regimens may be considered in this population with most studies evaluating the use of DTG and bictegravir without baseline INSTI RAMs. Future studies should include heavily treatment-experienced patients with a variety of baseline RAMs and a larger sample size.

Lamivudine-based maintenance antiretroviral therapies in patients living with HIV-1 with suppressed HIV RNA: derivation of a predictive score for virological failure.

Two-drug antiretroviral regimens based on lamivudine (3TC) plus either a protease inhibitor (PI) or dolutegravir (DTG) are becoming increasingly popular in switch strategies. Our goal was to derive a predictive score for virological failure (VF). We retrospectively analysed data for a cohort of 587 virologically suppressed (HIV RNA <37 HIV-1 RNA copies/mL), adult (≥18years old) patients starting lamivudine plus either a boosted PI or dolutegravir. Predictors of VF (defined as a single HIV RNA measurement ≥1000 copies/mL or two consecutive HIV RNA measurements ≥50 copies/mL) were identified using a multivariate Cox regression model. A 'weighted' score was assigned to each variable associated with VF; the discriminative power of the score obtained was expressed as the area under the receiver-operator characteristic curve (ROC-AUC). During a median 2years of follow-up time, 35 VFs occurred; predictors of VF were baseline residual HIV RNA between 20 and 36 copies/mL, African ethnicity, ≥10 therapeutic lines, the presence of at least one resistance-associated mutation (RAM) for resistance to current drugs (excluding M184V), a non-B viral subtype and a baseline CD4 count <200 cells/μL. A score of 2 was assigned to non-B viral subtype, 3 to residual viraemia ≥20 copies/mL, ≥10 previous therapeutic lines and African ethnicity, 4 to baseline CD4 count <200 cells/μL, and 7 to the presence of at least one RAM (excluding M184V). The ROC-AUC was 0.67 (95% confidence interval 0.57-0.77). The presence of at least one RAM, higher residual viraemia and African ethnicity were among the major predictors of VF in our cohort. Studies with larger sample sizes are warranted to improve the predictive value of the derived score.

Dolutegravir Monotherapy: One Is Not Enough

Accumulating data indicate that some two-drug antiretroviral regimens are effective in treating HIV. Monotherapy, however, has been dogged by concerns

Efficacy of a Two-Drug ART Regimen for Initial HIV Therapy

Increasing data support use of certain two-drug antiretroviral (ART) regimens for maintenance therapy for select HIV-infected patients suppressed on a

DGI-015 Assessment of the Treatment with a Two-Drug Antiretroviral Regimen

Background Antiretroviral treatment with a three drug-regimen is the initial treatment recommended for chronic HIV infection. For various reasons, the combination of three drugs can be modified to a two-drug...

Evaluation of disease patterns, treatment and prognosis of tuberculosis in AIDS patient.

Patterns of disease, diagnosis, treatment and prognosis of tuberculosis in 100 patients co-infected with AIDS at Casa da AIDS clinic was studied. Demographic characteristics were as follows: 76 male patients, 24 female patients, 67 caucasian, average 35.8 years-old (SD +/- 8.5). Sexual transmission of HIV was reported in 68 patients. Pulmonary tuberculosis was seen in 40 patients, extrapulmonary in 11, and combined in 49 patients. In 63 patients, TCD(4)(+) counts were below 200/mm(3) when tuberculosis was diagnosed. Fifty-five patients had their diagnoses confirmed by bacteriological identification of Mycobacterium; either through direct observation and/or culture. Tuberculosis was treated with rifampin, isoniazid and pyrazinamide in 60 patients, reinforced treatment in 14 and alternative treatment in the other 13 patients. Tuberculosis therapy lasted up to 9 months in 66% of the patients. Fifty-four patients were treated with a two-drug antiretroviral regimen and the remaining 46 patients received a triple regimen, which included a protease inhibitor. Among the latter, 35 patients were co-treated with rifampin. The occurrence of hepatic liver enzyme abnormalities was statistically related to alternative antiretroviral regimens (p = 0.01) and to the co-administration of rifampin and protease inhibitor (p = 0.019). Clinical resolution of tuberculosis was obtained in 74 patients. Twelve patients died during tuberculosis treatment. Resolution of tuberculosis was statistically significant related to antituberculosis treatment adherence (p = 0.001). The risk of no response to the treatment was 1.84 times more frequent among patients treated with alternative regimens regardless of the duration of the therapy. We conclude that the characteristics of tuberculosis in HIV infected patients requires that special attention be directed to the types and duration of both antiretroviral and anti-TB therapy in order to achieve the highest level of care.