ritonavir and abacavir--lamivudine-drug-combination

This systematic review aimed to assess the safety and efficacy of antiretroviral options for postexposure prophylaxis (PEP). Recognizing the limited data on the safety and efficacy of antiretroviral drugs for PEP in children, this review was extended to include consideration of data on the use of antiretroviral drugs for treatment of infants and children living with human immunodeficiency virus.. The PEP literature was assessed to identify studies reporting safety and completion rates for children given PEP, and this information was complemented by safety and efficacy data for drugs used in antiretroviral therapy. The proportion of patients experiencing each outcome was calculated and data were pooled using random-effects meta-analysis.. Three prospective cohort studies reported outcomes of children given zidovudine (ZDV) plus lamivudine (3TC) as a 2-drug PEP regimen. The proportion of children completing the full 28-day course of PEP was 64.0% (95% confidence interval [CI], 41.2%-86.8%), whereas the proportion discontinuing due to adverse events was 4.5% (95% CI, .4%-8.6%). One randomized trial compared abacavir (ABC) plus lamivudine (3TC) and ZDV+3TC as part of a dual or triple first-line antiretroviral therapy regimen; this study showed better efficacy in the ABC-containing combinations and no difference in the time to first serious adverse event. Three randomized trials compared lopinavir/ritonavir (LPV/r) to nevirapine (NVP) for antiretroviral therapy and showed a lower risk of treatment discontinuations associated with LPV/r vs NVP (hazard ratio, 0.56 [95% CI, .41-.75]) but no difference in drug-related adverse events. The overall quality of the evidence was rated as very low.. This review supports ZDV+3TC+LPV/r as the preferred 3-drug regimen for PEP in children.

Topics: Anti-HIV Agents; Child; Child, Preschool; Cohort Studies; Dideoxynucleosides; Drug Combinations; Female; HIV Infections; Humans; Infant; Infectious Disease Transmission, Vertical; Lamivudine; Lopinavir; Nevirapine; Post-Exposure Prophylaxis; Pregnancy; Prospective Studies; Randomized Controlled Trials as Topic; Ritonavir; Zidovudine

A network meta-analysis can provide estimates of relative efficacy for treatments not directly studied in head-to-head randomized controlled trials. We estimated the relative efficacy and safety of dolutegravir (DTG) versus third agents currently recommended by guidelines, including ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV), cobicistat-boosted elvitegravir (EVG/c), ritonavir-boosted lopinavir (LPV/r), raltegravir (RAL), and rilpivirine (RPV), in treatment-naive HIV-1-infected patients.. A systematic review of published literature was conducted to identify phase 3/4 randomized controlled clinical trials (up to August 2013) including at least one third agent of interest in combination with a backbone nucleoside reverse transcriptase inhibitor (NRTI) regimen. Bayesian fixed-effect network meta-analysis models adjusting for the type of nucleoside reverse transcriptase inhibitor backbone (tenofovir disoproxil fumarate/emtricitabine [TDF/FTC] or abacavir/lamivudine [ABC/3TC]) were used to evaluate week 48 efficacy (HIV-RNA suppression to <50 copies/mL and change in CD4+ cells/µL) and safety (lipid changes, adverse events, and discontinuations due to adverse events) of DTG relative to all other treatments. Sensitivity analyses assessing the impact of NRTI treatment adjustment and random-effects models were performed.. Thirty-one studies including 17,000 patients were combined in the analysis. Adjusting for the effect of NRTI backbone, treatment with DTG resulted in significantly higher odds of virologic suppression (HIV RNA<50 copies/mL) and increase in CD4+ cells/µL versus ATV/r, DRV/r, EFV, LPV/r, and RPV. Dolutegravir had better or equivalent changes in total cholesterol, LDL, triglycerides, and lower odds of adverse events and discontinuation due to adverse events compared to all treatments. Random-effects and unadjusted models resulted in similar conclusions.. Three clinical trials of DTG have demonstrated comparable or superior efficacy and safety to DRV, RAL, and EFV in HIV-1-infected treatment-naive patients. This network meta-analysis suggests DTG is also favorable or comparable to other commonly used third agents (ATV/r, LPV/r, RPV, and EVG/c).

Topics: Adenine; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Deoxycytidine; Dideoxynucleosides; Drug Combinations; Emtricitabine; Heterocyclic Compounds, 3-Ring; HIV Infections; HIV-1; Humans; Lamivudine; Lipids; Lopinavir; Nitriles; Organophosphonates; Oxazines; Piperazines; Pyridones; Pyrimidines; Pyrrolidinones; Raltegravir Potassium; Randomized Controlled Trials as Topic; Rilpivirine; Ritonavir; Tenofovir; Time Factors; Treatment Outcome; Viral Load

Human immunodeficiency virus (HIV)-associated neurocognitive disorders can persist in many patients despite achieving viral suppression while on antiretroviral therapy (ART). Neurocognitive function over 48 weeks was evaluated using a Cogstate test battery assessing psychomotor function, attention, learning, and working memory in 293 HIV-1-infected, ART-experienced, and virologically suppressed adults. The ASSURE study randomized participants 1:2 to remain on tenofovir/emtricitabine (TDF/FTC) and ritonavir-boosted atazanavir (ATV/r) or simplify to abacavir/lamivudine + atazanavir (ABC/3TC + ATV). Neurocognitive z-scores were computed using demographically adjusted normative data and were classified as "impaired" (defined as either a z-score ≤ - 2 or having 2 or more standardized individual test z-scores ≤ - 1); while higher scores (equaling better performance) were classified as "normal". By z-scores, 54.7% of participants had impaired neurocognition at baseline and 50.2% at week 48. There were no significant differences (p < 0.05) in the baseline-adjusted performance between treatment groups for any individual test or by z-score. Specific demographic and medical risk factors were evaluated by univariate analysis for impact on neurocognitive performance. Factors with p < 0.10 were evaluated by backwards regression analysis to identify neurocognition-correlated factors after accounting for treatment, assessment, and baseline. Four risk factors at baseline for impaired neurocognition were initially identified: lower CD4 nadir lymphocyte counts, higher Framingham risk scores, and interleukin-6 levels, and a history of psychiatric disorder not otherwise specified, however none were found to moderate the effect of treatment on neurocognition. In this aviremic, treatment-experienced population, baseline-adjusted neurocognitive function remained stable and equivalent over 48 weeks with both TDF/FTC + ATV/r-treated and in the ART-simplified ABC/3TC + ATV treatment groups.

Topics: Adult; Aged; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cognition; Dideoxynucleosides; Drug Combinations; Emtricitabine; Female; HIV Infections; Humans; Interleukin-6; Lamivudine; Male; Memory, Short-Term; Middle Aged; Neuropsychological Tests; Prospective Studies; Ritonavir; Tenofovir

The 2016 World Health Organization guidelines recommend all children <3 years start antiretroviral therapy (ART) on protease inhibitor-based regimens. But lopinavir/ritonavir (LPV/r) syrup has many challenges in low-income countries, including limited availability, requires refrigeration, interactions with anti-tuberculous drugs, twice-daily dosing, poor palatability in young children, and higher cost than non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. Successfully initiating LPV/r-based ART in HIV-infected children aged <2 years raises operational challenges that could be simplified by switching to a protease inhibitor-sparing therapy based on efavirenz (EFV), although, to date, EFV is not recommended in children <3 years.. The MONOD ANRS 12026 study is a phase 3 non-inferiority open-label randomised clinical trial conducted in Abidjan, Côte d'Ivoire, and Ouagadougou, Burkina Faso (ClinicalTrial.gov registry: NCT01127204). HIV-1-infected children who were tuberculosis-free and treated before the age of 2 years with 12-15 months of suppressive twice-daily LPV/r-based ART (HIV-1 RNA viral load (VL) <500 copies/mL, confirmed) were randomised to two arms: once-daily combination of abacavir (ABC) + lamivudine (3TC) + EFV (referred to as EFV) versus continuation of the twice-daily combination zidovudine (ZDV) or ABC + 3TC + LPV/r (referred to as LPV). The primary endpoint was the difference in the proportion of children with virological suppression by 12 months post-randomisation between arms (14% non-inferiority bound, Chi-squared test).. Between May 2011 and January 2013, 156 children (median age 13.7 months) were initiated on ART. After 12-15 months on ART, 106 (68%) were randomised to one of the two treatment arms (54 LPV, 52 EFV); 97 (91%) were aged <3 years. At 12 months post-randomisation, 46 children (85.2%) from LPV versus 43 (82.7%) from EFV showed virological suppression (defined as a VL <500 copies/mL; difference, 2.5%; 95% confidence interval (CI), -11.5 to 16.5), whereas seven (13%) in LPV and seven (13.5%) in EFV were classed as having virological failure (secondary outcome, defined as a VL ≥1000 copies/mL; difference, 0.5%; 95% CI, -13.4 to 12.4). No significant differences in adverse events were observed, with two adverse events in LPV (3.7%) versus four (7.7%) in EFV (p = 0.43). On genotyping, 13 out of 14 children with virological failure (six out of seven EFV, seven out of seven LPV) had a drug-resistance mutation: nine (five out of six EFV, four out of seven LPV) had one or more major NNRTI-resistance mutations whereas none had an LPV/r-resistance mutation.. At the VL threshold of 500 copies/mL, we could not conclusively demonstrate the non-inferiority of EFV on viral suppression compared to LPV because of low statistical power. However, non-inferiority was confirmed for a VL threshold of <1000 copies/mL. Resistance analyses highlighted a high frequency of NNRTI-resistance mutations. A switch to an EFV-based regimen as a simplification strategy around the age of 3 years needs to be closely monitored.. ClinicalTrial.gov registry n° NCT01127204 , 19 May 2010.

Topics: Alkynes; Anti-HIV Agents; Benzoxazines; Burkina Faso; Child, Preschool; Cote d'Ivoire; Cyclopropanes; Dideoxynucleosides; Drug Combinations; Drug Therapy, Combination; Female; Genotype; HIV Infections; HIV-1; Humans; Infant; Infant, Newborn; Lamivudine; Lopinavir; Male; Reverse Transcriptase Inhibitors; Ritonavir; Treatment Outcome; Viral Load

Switching from PIs to dolutegravir in virologically suppressed HIV-infected individuals has not been assessed.. The principal aim was to assess the evolution of bone mineral density (BMD) when switching from a ritonavir-boosted PI to dolutegravir in HIV-infected patients with osteopenia or osteoporosis. The secondary objective was to assess the antiviral efficacy and safety of the switch therapy.. This randomized, multicentre study assessed changes in BMD, bone turnover markers, and antiviral efficacy and safety in 73 virologically suppressed patients with osteopenia/osteoporosis taking a ritonavir-boosted PI plus abacavir/lamivudine who were randomized to switch from PI to dolutegravir (DOLU group, n  =   37) or continue with a PI (PI group, n  =   36). Clinical Trials: NCT02577042.. One and three patients from the DOLU and PI groups, respectively, withdrew prematurely (unrelated to treatment). At 48 weeks, 97.3% versus 91.7%, respectively, maintained viral suppression (snapshot analysis, ITT, M = F). No significant differences were seen between the groups in percentage change from baseline to week 48 in femoral ( P  =   0.56) and lumbar spine ( P  =   0.29) BMD, although lumbar spine BMD improved by 1.43% (-1.36; 2.92) in the DOLU group [0.12% (-2.83; 2.89) in the PI group]. Bone marker values did not vary significantly. At week 48, triglycerides were lower ( P  <   0.001) and HDL cholesterol higher ( P  =   0.027) in the DOLU group.. Dolutegravir + Kivexa ® was safe and well-tolerated in virologically suppressed patients receiving a PI-based regimen. The lipid profile was better, albeit without significant changes in BMD, probably because of the short follow-up.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Bone Density; Dideoxynucleosides; Drug Combinations; Female; Heterocyclic Compounds, 3-Ring; HIV Infections; HIV Protease Inhibitors; Humans; Lamivudine; Lipids; Male; Middle Aged; Oxazines; Piperazines; Pyridones; Ritonavir; Viral Load

HIV treatment guidelines endorse switching or simplification of antiretroviral therapy in therapy-experienced patients with suppressed viraemia; ritonavir discontinuation may also enhance tolerability and reduce long-term adverse events (AEs). This open-label, multicentre, noninferiority study enrolled HIV-1-infected, treatment-experienced adults with confirmed HIV-1 RNA ≤ 75 HIV-1 RNA copies/mL currently receiving tenofovir/emtricitabine + atazanavir/ritonavir (TDF/FTC + ATV/r) for ≥ 6 months with no reported history of virological failure.. Participants were randomized 1:2 to continue current treatment or switch to abacavir/lamivudine + atazanavir (ABC/3TC + ATV). Endpoints included the proportion of participants with HIV-1 RNA < 50 copies/mL by time to loss of virological response (TLOVR), AEs, fasting lipids, and inflammatory, coagulation, bone and renal biomarkers.. After 48 weeks, 76% (152 of 199) of ABC/3TC + ATV-treated and 79% (77 of 97) of TDF/FTC + ATV/r-treated participants had HIV-1 RNA < 50 copies/mL (TLOVR; P = 0.564). Other efficacy analyses yielded similar results. Rates of new grade 2-4 AEs were 45% in both groups, but an excess of hyperbilirubinaemia made the rate of treatment-emergent grade 3-4 laboratory abnormalities higher with TDF/FTC + ATV/r (36%) compared with ABC/3TC + ATV (19%). Most fasting lipid levels remained stable over time; high-density lipoprotein (HDL) cholesterol increased modestly in ABC/3TC + ATV-treated participants. Bone and renal biomarkers improved significantly between baseline and week 48 in participants taking ABC/3TC + ATV and were stable in participants taking TDF/FTC + ATV/r. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment groups.. The ABC/3TC + ATV treatment-switch group had similar viral suppression rates up to 48 weeks to the TDF/FTC + ATV/r comparator group, with lower rates of moderate- to high-grade hyperbilirubinaemia and improvements in bone and renal biomarkers.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Biomarkers; Bone Density; CD4 Lymphocyte Count; Dideoxynucleosides; Drug Combinations; Drug Substitution; Female; HIV Infections; Humans; Kidney; Lamivudine; Lipids; Male; Middle Aged; Ritonavir; RNA, Viral; Treatment Outcome; Viral Load

The direct-acting antiviral regimen of 25 mg ombitasvir-150 mg paritaprevir-100 mg ritonavir once daily (QD) plus 250 mg dasabuvir twice daily (BID) is approved for the treatment of hepatitis C virus genotype 1 infection, including patients coinfected with human immunodeficiency virus. This study was performed to evaluate the pharmacokinetic, safety, and tolerability effects of coadministering the regimen of 3 direct-acting antivirals with two antiretroviral therapies (dolutegravir or abacavir plus lamivudine). Healthy volunteers (n = 24) enrolled in this phase I, single-center, open-label, multiple-dose study received 50 mg dolutegravir QD for 7 days or 300 mg abacavir plus 300 mg lamivudine QD for 4 days, the 3-direct-acting-antiviral regimen for 14 days, followed by the 3-direct-acting-antiviral regimen with dolutegravir or abacavir plus lamivudine for 10 days. Pharmacokinetic parameters were calculated to compare combination therapy with 3-direct-acting-antiviral or antiretroviral therapy alone, and safety/tolerability were assessed throughout the study. Coadministration of the 3-direct-acting-antiviral regimen increased the geometric mean maximum plasma concentration (Cmax) and the area under the curve (AUC) of dolutegravir by 22% (central value ratio [90% confidence intervals], 1.219 [1.153, 1.288]) and 38% (1.380 [1.295, 1.469]), respectively. Abacavir geometric mean Cmax and AUC values decreased by 13% (0.873 [0.777, 0.979]) and 6% (0.943 [0.901, 0.986]), while those for lamivudine decreased by 22% (0.778 [0.719, 0.842]) and 12% (0.876 [0.821, 0.934]). For the 3-direct-acting-antiviral regimen, geometric mean Cmax and AUC during coadministration were within 18% of measurements made during administration of the 3-direct-acting-antiviral regimen alone, although trough concentrations for paritaprevir were 34% (0.664 [0.585, 0.754]) and 27% (0.729 [0.627, 0.847]) lower with dolutegravir and abacavir-lamivudine, respectively. All study treatments were generally well tolerated, with no evidence of increased rates of adverse events during combination administration. These data indicate that the 3-direct-acting-antiviral regimen can be administered with dolutegravir or abacavir plus lamivudine without dose adjustment.

Topics: 2-Naphthylamine; Adult; Anilides; Anti-HIV Agents; Anti-Retroviral Agents; Carbamates; Cyclopropanes; Dideoxynucleosides; Drug Combinations; Drug Interactions; Female; Hepatitis C, Chronic; Heterocyclic Compounds, 3-Ring; HIV Infections; Humans; Lactams, Macrocyclic; Lamivudine; Macrocyclic Compounds; Male; Middle Aged; Oxazines; Piperazines; Proline; Pyridones; Ritonavir; Sulfonamides; Uracil; Valine

To compare the efficacy and safety of fixed-dose abacavir/lamivudine (ABC/3TC) and tenofovir/emtricitabine (TDF/FTC) with ritonavir-boosted atazanavir (ATV/r) in treatment-naïve Japanese patients with HIV-1 infection.. A 96-week multicenter, randomized, open-label, parallel group pilot study was conducted. The endpoints were times to virologic failure, safety event and regimen modification.. 109 patients were enrolled and randomly allocated (54 patients received ABC/3TC and 55 patients received TDF/FTC). All randomized subjects were analyzed. The time to virologic failure was not significantly different between the two arms by 96 weeks (HR, 2.09; 95% CI, 0.72-6.13; p=0.178). Both regimens showed favorable viral efficacy, as in the intention-to-treat population, 72.2% (ABC/3TC) and 78.2% (TDF/FTC) of the patients had an HIV-1 viral load <50 copies/mL at 96 weeks. The time to the first grade 3 or 4 adverse event and the time to the first regimen modification were not significantly different between the two arms (adverse event: HR 0.66; 95% CI, 0.25-1.75, p=0.407) (regimen modification: HR 1.03; 95% CI, 0.33-3.19, p=0.964). Both regimens were also well-tolerated, as only 11.1% (ABC/3TC) and 10.9% (TDF/FTC) of the patients discontinued the allocated regimen by 96 weeks. Clinically suspected abacavir-associated hypersensitivity reactions occurred in only one (1.9%) patient in the ABC/3TC arm.. Although insufficiently powered to show non-inferiority of viral efficacy of ABC/3TC relative to TDF/FTC, this pilot trial suggested that ABC/3TC with ATV/r is a safe and efficacious initial regimen for HLA-B*5701-negative patients, such as the Japanese population.

Topics: Adenine; Adult; Anti-HIV Agents; Antiviral Agents; Asian People; Atazanavir Sulfate; Deoxycytidine; Dideoxynucleosides; Drug Combinations; Emtricitabine; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Lamivudine; Male; Oligopeptides; Organophosphonates; Pilot Projects; Pyridines; Ritonavir; Tenofovir; Treatment Outcome

Rates of cardiovascular disease are higher among HIV-infected patients as a result of the complex interplay between traditional risk factors, HIV-related inflammatory and immunologic changes, and effects of antiretroviral therapy (ART). This study prospectively evaluated changes in cardiovascular biomarkers in an underrepresented, racially diverse, HIV-1-infected population receiving abacavir/lamivudine as backbone therapy.. This 96-week, open-label, randomized, multicenter study compared once-daily fosamprenavir/ritonavir 1400/100 mg and efavirenz 600 mg, both with ABC/3TC 600 mg/300 mg, in antiretroviral-naïve, HLA-B*5701-negative adults without major resistance mutations to study drugs. We evaluated changes from baseline to weeks 4, 12, 24, 48, and 96 in interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble vascular adhesion molecule-1 (sVCAM-1), d-dimer, plasminogen, and fibrinogen. Biomarker data were log-transformed before analysis, and changes from baseline were described using geometric mean ratios.. This study enrolled 101 patients (51 receiving fosamprenavir/ritonavir; 50 receiving efavirenz): 32% female, 60% African American, and 38% Hispanic/Latino; 66% (67/101) completed 96 weeks on study. At week 96, levels of IL-6, sVCAM-1, d-dimer, fibrinogen, and plasminogen were lower than baseline in both treatment groups, and the decrease was statistically significant for sVCAM-1 (fosamprenavir/ritonavir and efavirenz), d-dimer (fosamprenavir/ritonavir and efavirenz), fibrinogen (efavirenz), and plasminogen (efavirenz). Values of hs-CRP varied over time in both groups, with a significant increase over baseline at Weeks 4 and 24 in the efavirenz group. At week 96, there was no difference between the groups in the percentage of patients with HIV-1 RNA <50 copies/mL (fosamprenavir/ritonavir 63%; efavirenz 66%) by ITT missing-equals-failure analysis. Treatment-related grade 2-4 adverse events were more common with efavirenz (32%) compared with fosamprenavir/ritonavir (20%), and median lipid concentrations increased in both groups over 96 weeks of treatment.. In this study of underrepresented patients, treatment with abacavir/lamivudine combined with either fosamprenavir/ritonavir or efavirenz over 96 weeks, produced stable or declining biomarker levels except for hs-CRP, including significant and favorable decreases in thrombotic activity (reflected by d-dimer) and endothelial activation (reflected by sVCAM-1). Our study adds to the emerging data that some cardiovascular biomarkers are decreased with initiation of ART and control of HIV viremia.. ClinicalTrials.gov identifier NCT00727597.

Topics: Adolescent; Adult; Aged; Alkynes; Anti-HIV Agents; Benzoxazines; Biomarkers; C-Reactive Protein; Carbamates; Cyclopropanes; Dideoxynucleosides; Drug Combinations; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Furans; HIV Infections; Humans; Interleukin-6; Lamivudine; Male; Middle Aged; Organophosphates; Plasminogen; Prospective Studies; Ritonavir; Sulfonamides; Vascular Cell Adhesion Molecule-1; Young Adult

Propensity for developing coronary heart disease (CHD) is linked with Framingham-defined cardiovascular risk factors and elevated inflammatory biomarkers. Cardiovascular risk and inflammatory biomarkers were evaluated in ARIES, a Phase IIIb/IV clinical trial in which 515 antiretroviral-naive HIV-infected subjects initially received abacavir/lamivudine + atazanavir/ritonavir for 36 weeks. Subjects who were virologically suppressed by week 30 were randomized 1:1 at week 36 to either maintain or discontinue ritonavir for an additional 108 weeks. Framingham 10-year CHD risk scores (FRS) and risk category of <6% or ≥6%, lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) were assessed at baseline, week 84, and week 144. Biomarkers were stratified by FRS category. When ritonavir-boosted/nonboosted treatment groups were combined, median hsCRP did not change significantly between baseline (1.6 mg/liter) and week 144 (1.4 mg/liter) in subjects with FRS <6% (p=0.535) or with FRS ≥6% (1.9 mg/liter vs. 2.0 mg/liter, respectively; p=0.102). Median IL-6 was similar for subjects with FRS <6% (p=0.267) at baseline (1.6 pg/ml) and week 144 (1.4 pg/ml) and for FRS ≥6% (2.0 pg/ml vs. 2.2 pg/ml, respectively; p=0.099). Median Lp-PLA(2) decreased significantly (p<0.001) between baseline (197 nmol/min/ml) and week 144 (168 nmol/min/ml) in subjects with FRS <6% and with FRS ≥6% (238 nmol/min/ml vs. 175 nmol/min/ml, respectively; p<0.001). In conclusion, in antiretroviral-naive subjects treated with abacavir-based therapy for 144 weeks, median inflammatory biomarker levels for hsCRP and IL-6 generally remained stable with no significant difference between baseline and week 144 for subjects with either FRS <6% or FRS ≥6%. Lp-PLA(2) median values declined significantly over 144 weeks for subjects in either FRS stratum.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Adult; Aged; Anti-HIV Agents; Atazanavir Sulfate; Biomarkers; C-Reactive Protein; Coronary Disease; Dideoxynucleosides; Drug Combinations; Female; HIV Infections; Humans; Inflammation; Interleukin-6; Lamivudine; Lipids; Longitudinal Studies; Male; Middle Aged; Oligopeptides; Pyridines; Risk Assessment; Ritonavir; Treatment Outcome; Young Adult

The effect of nonthymidine nucleoside reverse-transcriptase inhibitors (NRTIs) on fat mitochondrial DNA (mtDNA) content and function is unclear.. A5202 randomized antiretroviral therapy-naive human immunodeficiency virus-infected subjects to abacavir-lamivudine (ABC/3TC) versus tenofovir DF-emtricitabine (TDF/FTC) with efavirenz (EFV) or atazanavir-ritonavir (ATV/r). A5224s, substudy of A5202, enrolled 269 subjects with fat measurements by dual-energy x-ray absorptiometry and computed tomography. A subset of subjects underwent fat biopsies at baseline and week 96 for mtDNA content (real-time polymerase chain reaction) and oxidative phosphorylation nicotinamide adenine dinucleotide (reduced) dehydrogenase (complex I) and cytochrome c oxidase (complex IV) activity levels (immunoassays). Intent-to-treat analyses were performed using analysis of variance and paired t tests.. Fifty-six subjects (87% male; median age, 39 years) were included; their median body mass index, CD4 cell count, and fat mtDNA level were 26 kg/m(2), 227 cells/μL, and 1197 copies/cell, respectively. Fat mtDNA content decreased within the ABC/3TC and TDF/FTC groups (combining EFV and ATV/r arms; median change, -341 [interquartile range, -848 to 190; P = .03] and -400 [-661 to -221; P < .001] copies/cell, respectively), but these changes did not differ significantly between the 2 groups (P = .57). Complex I and IV activity decreased significantly in the TDF/FTC group (median change, -12.45 [interquartile range, -24.70 to 2.90; P = .003] and -8.25 [-13.90 to -1.30; P < .001], optical density × 10(3)/µg, respectively) but not the ABC/3TC group. Differences between the ABC/3TC and TDF/FTC groups were significant for complex I (P = .03).. ABC/3TC and TDF/FTC significantly and similarly decreased fat mtDNA content, but only TDF/FTC decreased complex I and complex IV activity levels.. NCT00118898.

Topics: Adenine; Adipose Tissue; Adult; Alkynes; Anti-HIV Agents; Atazanavir Sulfate; Benzoxazines; Cyclopropanes; Deoxycytidine; Dideoxynucleosides; DNA, Mitochondrial; Drug Combinations; Drug Therapy, Combination; Emtricitabine; Female; HIV Infections; HIV-1; HIV-Associated Lipodystrophy Syndrome; Humans; Lamivudine; Male; Mitochondria; Oligopeptides; Organophosphonates; Pyridines; Reverse Transcriptase Inhibitors; Ritonavir; Tenofovir; Treatment Outcome

The effect of specific antiretrovirals on inflammation is unclear.. A5224s was a substudy of A5202, which randomized HIV-infected treatment-naïve patients to blinded abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or atazanavir/ritonavir (ATV/r) in a factorial design. Our analysis compared changes in inflammation markers from baseline to week 24 between ABC/3TC and TDF/FTC. Secondary analyses included changes at week 96 and comparisons of EFV vs. ATV/r.. Analyses included 244 patients (85% male, 48% white non-Hispanic), median age 39 years, HIV-1 RNA 4.6 log10 copies/ml, CD4 240 cells/μl. TNF-α, soluble receptors of TNF-α (sTNFR)-I and II, soluble vascular cellular adhesion molecule (sVCAM)-1 and soluble intercellular adhesion molecule (sICAM)-1 decreased significantly at weeks 24 and 96, without significant differences between components (P ≥ 0.44). At week 24, ABC/3TC had a greater high-sensitivity C-reactive protein (hsCRP) mean fold change than TDF/FTC {1.43 vs. 0.88, estimated mean fold change percentage difference [Δ] 61.5% [95% confidence interval (CI) 13.6%, 129.5%]; P = 0.008}. Similar results were seen at week 96 (P = 0.021). At week 24 (but not 96), EFV had a greater hsCRP mean fold change than ATV/r [1.41 vs. 0.88; Δ = 60.2% (12.6%, 127.7%); P = 0.009]. IL-6 decreased significantly at week 24 with TDF/FTC but not with ABC/3TC (between-components P = 0.019). At week 96, IL-6 decreased significantly in both nucleoside reverse transcriptase inhibitor components (between-components P = 0.11). IL-6 changes were not significantly different between ATV/r and EFV at either time point (P ≥ 0.89).. Soluble TNF-receptors and adhesion molecules decreased following treatment initiation and did not differ by regimens. Differences were seen on hsCRP and IL-6 changes with ABC/3TC vs. TDF/FTC and on hsCRP with EFV vs. ATV/r.

Topics: Acquired Immunodeficiency Syndrome; Adenine; Adult; Alkynes; Anti-HIV Agents; Atazanavir Sulfate; Benzoxazines; Biomarkers; C-Reactive Protein; Cyclopropanes; Deoxycytidine; Dideoxynucleosides; Drug Combinations; Emtricitabine; Female; HIV-1; Humans; Inflammation; Interleukin-6; Lamivudine; Male; Oligopeptides; Organophosphonates; Pyridines; Ritonavir; Tenofovir; Tumor Necrosis Factor-alpha

The aim of this study was to investigate the effect on fasting lipid parameters of switching to tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) from abacavir (ABC) plus lamivudine (3TC; both fixed-dose combinations), while maintaining ritonavir-boosted lopinavir (LPV/r).. This was an open-label randomized two-arm 12-week controlled study in virologically suppressed HIV-infected patients with elevated cholesterol (≥5.2 mmol/l). Patients stable on ABC/3TC plus LPV/r either continued treatment or switched to TDF/FTC plus LPV/r for 12 weeks. Standard efficacy and safety end points (including fasting lipids) were assessed.. In total, 85 subjects were treated (n=42 ABC/FTC and n=43 TDF/3TC). A statistically significant decrease in total cholesterol was observed in the TDF/FTC group: from median (IQR) 6.22 mmol/l (5.91-6.77) at baseline to 5.75 mmol/l (5.04-6.18) at week 12 (median [IQR] change from baseline -0.73 mmol/l [-1.20- -0.18]; P<0.001). No notable change was observed for the ABC/3TC group. The difference between groups at week 12 was -0.82 mmol/l (P<0.001). For TDF/FTC (but not for ABC/3TC), statistically significant reductions (P<0.05) from baseline were observed in total, low-density lipoprotein, high-density lipoprotein (HDL)- and non-HDL cholesterol (at weeks 4 and 12). Statistically significant decreases were observed in median estimated creatinine clearance (Cockcroft-Gault) from baseline to week 12 for patients who switched to TDF/FTC (-5.47 ml/min) versus the ABC/3TC group (-2.15 ml/min; P=0.016 between groups). Virological suppression was maintained in both groups. No new safety issues were identified.. Switching to TDF/FTC from ABC/3TC was associated with rapid improvements in fasting lipid parameters and continued virological control in patients receiving LPV/r as the third component of antiretroviral therapy. The effect of these changes on clinical end points remains unclear and would need to be evaluated in a longer-term study.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Cholesterol; Deoxycytidine; Dideoxynucleosides; Drug Combinations; Drug Substitution; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV; HIV Infections; Humans; Lamivudine; Lipids; Lopinavir; Male; Medication Adherence; Middle Aged; Organophosphorus Compounds; Ritonavir; Treatment Outcome

Long-term effects of abacavir (ABC)-lamivudine (3TC), compared with tenofovir (TDF)-emtricitabine (FTC) with efavirenz (EFV) or atazanavir plus ritonavir (ATV/r), on bone mineral density (BMD) have not been analyzed.. A5224s was a substudy of A5202, in which HIV-infected treatment-naive participants were randomized and blinded to receive ABC-3TC or TDF-FTC with open-label EFV or ATV/r. Primary bone end points included Dual-emission X-ray absorbtiometry (DXA)-measured percent changes in spine and hip BMD at week 96. Primary analyses were intent-to-treat. Statistical tests used the factorial design and included linear regression, 2-sample t, log-rank, and Fisher's exact tests.. Two hundred sixty-nine persons randomized to 4 arms of ABC-3TC or TDF-FTC with EFV or ATV/r. At baseline, 85% were male, and 47% were white non-Hispanic; the median HIV-1 RNA load was 4.6 log(10) copies/mL, the median age was 38 years, the median weight was 76 kg, and the median CD4 cell count was 233 cells/μL. At week 96, the mean percentage changes from baseline in spine and hip BMD for ABC-3TC versus TDF-FTC were -1.3% and -3.3% (P = .004) and -2.6% and -4.0% (P = .024), respectively; and for EFV versus ATV/r were -1.7% and -3.1% (P = .035) and -3.1% and -3.4% (P = .61), respectively. Bone fracture was observed in 5.6% of participants. The probability of bone fractures and time to first fracture were not different across components.. Compared with ABC-3TC, TDF-FTC-treated participants had significantly greater decreases in spine and hip BMD, whereas ATV/r led to more significant losses in spine, but not hip, BMD than EFV. Clinical Trials Registration. NCT00118898.

Topics: Absorptiometry, Photon; Adenine; Adult; Alkynes; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Benzoxazines; Bone Density; CD4 Lymphocyte Count; Cyclopropanes; Deoxycytidine; Dideoxynucleosides; Drug Combinations; Drug Therapy, Combination; Emtricitabine; Female; Fractures, Bone; HIV Infections; Humans; Intention to Treat Analysis; Lamivudine; Male; Middle Aged; Oligopeptides; Organophosphonates; Osteoporosis; Pyridines; Risk Factors; Ritonavir; Tenofovir; Viral Load

Although efavirenz and lopinavir/ritonavir(r) are both recommended antiretroviral agents in antiretroviral-naïve HIV-infected patients, there are few randomized comparisons of their efficacy and tolerability.. A multicenter and randomized study was performed including 126 antiretroviral-naïve patients, randomly assigned to efavirenz+Kivexa (n=63) or lopinavir/r+Kivexa (n=63). Efficacy endpoints were the percentage of patients with HIV-RNA < or =50 copies/mL at week 48 and CD4 recovery. Safety was assessed by comparing toxicity and discontinuations. Statistical analyses were performed on an intention-to-treat (ITT) basis (Missing=Failure).. At week 48, 56.7% of patients in the efavirenz and 63.2% in the lopinavir/r groups showed HIV-1 RNA <50 copies/mL (P=0.770) (intention-to-treat analysis; Missing=Failure). Only 1 (1.53%) patient from each group experienced virological failure. CD4 values increased in both groups (298 cells in the efavirenz group, P=0.001; 249 cells in the lopinavir/r group, P=0.002; P=0.126 between groups). HDL-cholesterol only increased in the efavirenz group (from 39+/-12 mg/dL to 49+/-11; P=0.001). Discontinuations were more frequent in the lopinavir/r group (36.5% versus 28.5%; P=0.193), but more patients with efavirenz interrupted due to toxicity (11.1% versus 6.3%); most of them were attributed to hypersensitivity reaction.. Similar virological efficacy was observed for efavirenz and lopinavir/r, when administered with Kivexa in antiretroviral-naïve patients, while immunological improvement was slightly superior for efavirenz. The higher rate of discontinuation due to toxicity in the efavirenz group was related to a higher incidence of hypersensitivity reaction. Nowadays, the use of the new formulation of lopinavir/r and the HLA-B*5701 genotype test before starting abacavir should improve the safety profiles of these regimens.

Topics: Adult; Alkynes; Anti-HIV Agents; Benzoxazines; CD4 Lymphocyte Count; Cyclopropanes; Dideoxynucleosides; Drug Combinations; Drug Hypersensitivity; Female; HIV Infections; Humans; Lamivudine; Lopinavir; Male; Middle Aged; Pyrimidinones; Ritonavir; RNA, Viral; Treatment Outcome; Viral Load; Withholding Treatment

Cryptococcal meningitis (CCM) is a common and deadly disease among HIV-infected patients. Notable about CCM is its association with the immune reconstitution inflammatory syndrome (IRIS). Though it has been posited a switch from first to second-line antiretroviral therapy (ART) can induce CCM IRIS, a case presentation of CCM IRIS has not been published.. A 10-year-old, HIV-infected girl who initially presented with severe headache and new-onset seizures, with cerebrospinal fluid that returned antigen, India Ink, and culture positive for Cryptococcus neoformans. Notably, 8 weeks prior to seizures, she had switched from first line to second-line ART (abacavir-lamivudine-efavirenz to zidovudine-lamivudine-lopinavir/ritonavir) due to virologic failure, with a viral load of 224,000 copies/milliliter. At time of seizures and 8 weeks on second-line ART, her viral load had reduced to 262 copies/milliliter. Her hospital course was prolonged, as she had ongoing headaches and developed bilateral cranial nerve VI palsies despite clearance of Cryptococcus from cerebrospinal fluid on antifungal therapy and therapeutic lumbar punctures. However, symptoms stabilized, and she was discharged with oral fluconazole. Cranial nerve palsies resolved 10 weeks post discharge and she has remained disease free.. We describe a case of CCM IRIS in a 10-year-old HIV infected child after changing to second-line ART. This case provides evidence that screening for cryptococcal antigenaemia prior to switch from first-line to second-line ART could be an important measure to prevent cryptococcal disease.

Topics: AIDS-Related Opportunistic Infections; Alkynes; Anti-HIV Agents; Antifungal Agents; Antigens, Fungal; Benzoxazines; Child; Cryptococcus neoformans; Cyclopropanes; Dideoxynucleosides; Drug Combinations; Female; Fluconazole; HIV; Humans; Immune Reconstitution Inflammatory Syndrome; Lamivudine; Lopinavir; Meningitis, Cryptococcal; Ritonavir; Treatment Outcome; Viral Load; Zidovudine

Ergotism is an ischaemic complication due to vasoconstriction throughout the body due to ingestion of ergotamine. A 34-year-old Hispanic man with HIV infection treated with saquinavir, ritonavir and abacavir/lamivudine presented to the emergency department complaining of left foot pain 1 week prior to admission. The affected extremity was cold with absence of pedal and tibial pulses. Arterial Doppler revealed absent arterial flow from the popliteal artery later confirmed by arteriography. Medication reconciliation revealed a recent prescription for migraine headache containing ergotamine. Drug was discontinued and the patient was started on cilostazol, enoxaparin and nitroglycerin patches on the affected limb. Complete resolution of symptoms and arteriography findings occurred 2 days after therapy began.

Topics: Adult; Anti-HIV Agents; Anticoagulants; Cilostazol; Cytochrome P-450 CYP3A Inhibitors; Dideoxynucleosides; Drug Combinations; Drug Interactions; Enoxaparin; Ergotamine; Ergotism; Headache; HIV Infections; Humans; Ischemia; Lamivudine; Lower Extremity; Male; Nitroglycerin; Ritonavir; Saquinavir; Tetrazoles; Tibial Arteries; Ultrasonography, Doppler, Color; Vasoconstrictor Agents; Vasodilator Agents

The standard of care for HIV treatment is a three-drug regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and either a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor (PI) or an integrase strand transfer inhibitor. Darunavir boosted with ritonavir (DRV/r) is the only preferred PI in the US Department of Health and Human Services (DHHS) HIV treatment guidelines for antiretroviral-naïve patients, recommended in combination with tenofovir/emtricitabine for antiretroviral-naïve patients. For treatment-experienced and certain antiretroviral-naïve patients, abacavir and lamivudine (ABC/3TC) in combination with DRV/r is considered an effective and tolerable alternative, despite limited research on the effectiveness of this particular combination. This study evaluated virologic outcomes in treatment-experienced patients taking ABC/3TC + DRV/r compared to treatment-experienced patients taking ABC/3TC with any other PI.. A total of 151 patients initiating ABC/3TC + DRV/r and 525 patients initiating ABC/3TC + a non-darunavir PI were included. Patients in both treatment groups had comparable clinical indicators (viral load, CD4) at baseline. A regimen of ABC/3TC + DRV/r was more likely to be prescribed in the later years of the study period, leading to a shorter median follow-up in the DRV/r treatment group (as-treated analysis: 14 vs. 17 months, p = 0.04; intent-to-treat analysis: 33 vs. 68 months, p < 0.001). Multivariable logistic regression models accounting for year of regimen initiation, among other factors, indicated no statistically significant differences in achieving an undetectable viral load for patients taking DRV/r with ABC/3TC compared with other PIs, both in the as-treated (odds ratio [95 % confidence interval]: 0.84 [0.53-1.34]) and intent-to-treat analyses (0.82 [0.48-1.40]). Patients in both treatment groups also showed similar reductions in viral load (median darunavir vs. non-darunavir: -23.0 vs. -23.0 copies/mL; p = 0.72) and gains in CD4 T cell counts (median darunavir vs. non-darunavir: 106 vs. 108 cells/mm. Patients receiving ABC/3TC + DRV/r appear to experience similar treatment benefit to patients taking ABC/3TC with other PIs in terms of achieving suppression, as well as absolute reductions in viral load and CD4 lymphocyte gains.

Topics: Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Darunavir; Dideoxynucleosides; Drug Combinations; Female; HIV Infections; HIV Protease Inhibitors; Humans; Lamivudine; Male; Middle Aged; Prospective Studies; Ritonavir; Viral Load

New Direct-acting Antiviral Agents (DAA)-based anti-HCV therapies currently provide extraordinary opportunities to cure patients. Drug-drug interactions are however a real challenge during treatment. In particular, in HIV-infected patients in cART, DAA choice is limited by such interactions, which can result both in reduced efficacy and toxicity. We report the case of a HIV-infected patient on cART with atazanavir/ritonavir/abacavir/lamivudine, who presented kidney and biliary lithiasis, the latter treated with endoscopic retrograde cholangiopancreatography and endoscopic biliary sphincterotomy, after beginning anti-HCV treatment with daclatasvir/sofosbuvir/ribavirin. Hyperbilirubinemia with or without jaundice is a well known side effect of atazanavir, because of its inhibition of uridine diphosphate-glucuronosyl transferase. We speculate that in this case hyperbilirubinemia worsening was due to atazanavir/ribavirin co-administration. However, pharmacokinetic data are lacking about atazanavir/daclatasvir concomitant administration in real life setting.

Topics: Adult; Anti-HIV Agents; Antiviral Agents; Atazanavir Sulfate; Biliary Tract Diseases; Carbamates; Coinfection; Dideoxynucleosides; Drug Combinations; Drug Interactions; Genotype; Hepacivirus; Hepatitis C; HIV Infections; Humans; Imidazoles; Kidney Calculi; Lamivudine; Lithiasis; Male; Pyrrolidines; Ribavirin; Ritonavir; Sofosbuvir; Valine

Effectiveness data of an unboosted atazanavir (ATV) with abacavir/lamivudine (ABC/3TC) switch strategy in clinical routine are scant.We evaluated treatment outcomes of ATV + ABC/3TC in pretreated subjects in the EuroSIDA cohort when started with undetectable plasma HIV-1 viral load (pVL), performing a time to loss of virological response (TLOVR <50 copies/mL) and a snapshot analysis at 48, 96, and 144 weeks. Virological failure (VF) was defined as confirmed pVL >50 copies/mL.We included 285 subjects, 67% male, with median baseline CD4 530 cells, and 44 months with pVL ≤50 copies/mL. The third drug in the previous regimen was ritonavir-boosted atazanavir (ATV/r) in 79 (28%), and another ritonavir-boosted protease inhibitor (PI/r) in 29 (10%). Ninety (32%) had previously failed with a PI. Proportions of people with virological success at 48/96/144 weeks were 90%/87%/88% (TLOVR) and 74%/67%/59% (snapshot analysis), respectively. The rates of VF were 8%/8%/6%. Rates of adverse events leading to study discontinuation were 0.4%/1%/2%. The multivariable adjusted analysis showed an association between VF and nadir CD4+ (hazard ratio [HR] 0.63 [95% confidence interval [CI]: 0.42-0.93] per 100 cells higher), time with pVL ≤50 copies/mL (HR 0.87 [95% CI: 0.79-0.96] per 6 months longer), and previous failure with a PI (HR 2.78 [95% CI: 1.28-6.04]). Resistance selection at failure was uncommon.A switch to ATV + ABC/3TC in selected subjects with suppressed viremia was associated with low rates of VF and discontinuation due to adverse events, even in subjects not receiving ATV/r. The strategy might be considered in those with long-term suppression and no prior PI failure.

Topics: Adult; Age Factors; Anti-HIV Agents; Atazanavir Sulfate; Dideoxynucleosides; Drug Combinations; Drug Therapy, Combination; Female; HIV Protease Inhibitors; HIV-1; Humans; Lamivudine; Male; Middle Aged; Prospective Studies; Ritonavir; Sex Factors; Viral Load

Lopinavir/ritonavir (LPV/r) is available in a liquid formulation that is far from ideal for treatment of children in resource-poor settings. Flexible, low-cost, solid, oral fixed-dose combinations (FDC) of LPV/r with nucleoside reverse transcriptase inhibitors (LPV/r/abacavir [ABC]/lamivudine [3TC] and LPV/r/zidovudine [ZDV]/3TC) are needed to improve both management and adherence of children. This work aimed to develop appropriate drug ratios and dosing for each FDC.. Data from 25 combined datasets included therapeutic drug monitoring and clinical studies from IMPAACT and PENTA. Population pharmacokinetic analyses were performed using Monolix. Monte-Carlo simulations of WHO and FDA dosing recommendations were performed to assess their ability to provide optimal exposure in children weighing 4 to 25 kg based on consensus plasma targets. The LPV/r:3TC:ZDV(ABC) dose ratios were 2.67:1:2(2), respectively.. Using WHO dosage, LPV efficacy target was reached in all weight bands. Given the recommended drug ratios, the dosage for the 4-5.9 kg weight band (LPV/ZDV: 120/90 mg twice daily [bid]) showed more than 20% of subjects had ZDV levels at high risk of neutropenia. Reducing the LPV/ZDV dose to 80/60 mg bid decreased frequency of high ZDV concentrations but retained the LPV efficacy criteria.. This defined a flexible and simple FDC containing 40 mg LPV, 10 mg ritonavir, 15 mg 3TC and 30 mg ABC or ZDV. According to the weight bands defined by WHO, 4-5.9 kg, 6-9.9 kg, 10-13.9 kg, 14-19.9 kg, 20-24.9 kg, therapeutic doses would be 2, 3, 4, 5 or 6 individual units administered by oral route bid.

Topics: Administration, Oral; Adolescent; Age Factors; Antiretroviral Therapy, Highly Active; Biological Availability; Child; Child, Preschool; Clinical Trials as Topic; Computer Simulation; Dideoxynucleosides; Drug Combinations; Drug Dosage Calculations; Drug Monitoring; Female; HIV Infections; HIV-1; Humans; Infant; Lamivudine; Lopinavir; Male; Models, Statistical; Ritonavir; Silybin; Silymarin; Viral Load; Zidovudine

Dolutegravir (DTG) has been studied in three trials in HIV treatment-naive participants, showing noninferiority compared with raltegravir (RAL), and superiority compared with efavirenz and ritonavir-boosted darunavir. We explored factors that predicted treatment success, the consistency of observed treatment differences across subgroups and the impact of NRTI backbone on treatment outcome.. Retrospective exploratory analyses of data from three large, randomized, international comparative trials: SPRING-2, SINGLE, and FLAMINGO.. We examined the efficacy of DTG in HIV-infected participants with respect to relevant demographic and HIV-1-related baseline characteristics using the primary efficacy endpoint from the studies (FDA snapshot) and secondary endpoints that examine specific elements of treatment response. Regression models were used to analyze pooled data from all three studies.. Snapshot response was affected by age, hepatitis co-infection, HIV risk factor, baseline CD4⁺ cell count, and HIV-1 RNA and by third agent. Differences between DTG and other third agents were generally consistent across these subgroups. There was no evidence of a difference in snapshot response between abacavir/lamivudine (ABC/3TC) and tenofovir/emtricitabine (TDF/FTC) overall [ABC/3TC 86%, TDF/FTC 85%, difference 1.1%, confidence interval (CI) -1.8, 4.0 percentage points, P = 0.61] or at high viral loads (difference -2.5, 95% CI -8.9, 3.8 percentage points, P = 0.42).. DTG is a once-daily, unboosted integrase inhibitor that is effective in combination with either ABC/3TC or TDF/FTC for first-line antiretroviral therapy in HIV-positive individuals with a variety of baseline characteristics.

Topics: Adenine; Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Clinical Trials, Phase III as Topic; Coinfection; Deoxycytidine; Dideoxynucleosides; Drug Combinations; Emtricitabine; Female; Heterocyclic Compounds, 3-Ring; HIV Infections; HIV Integrase Inhibitors; HIV Protease Inhibitors; HIV-1; Humans; Lamivudine; Male; Organophosphonates; Oxazines; Piperazines; Pyridones; Pyrrolidinones; Raltegravir Potassium; Randomized Controlled Trials as Topic; Regression Analysis; Retrospective Studies; Ritonavir; Tenofovir; Treatment Outcome; Viral Load

Topics: Anti-Bacterial Agents; Clarithromycin; Death, Sudden, Cardiac; Dideoxynucleosides; Drug Combinations; Drug Interactions; Electrocardiography; Fatal Outcome; HIV Infections; Humans; Lamivudine; Lopinavir; Male; Middle Aged; Piperazines; Purines; Ritonavir; Sexual Behavior; Sildenafil Citrate; Sulfonamides; Vasodilator Agents

To present clinical experience with a regimen including abacavir/lamivudine + darunavir/ritonavir in a cohort of HIV-1-infected patients.. A retrospective, multicentre cohort study, including all consecutive adult HIV-1-infected patients who started abacavir/lamivudine + darunavir/ritonavir from April 2008 to December 2010 and had at least one follow-up visit. The primary endpoint was HIV-1 viral load (VL) <40 copies/mL at week 48.. One hundred and eighty-three patients (42 naive and 141 experienced) from 19 hospitals in Spain were studied. The median follow-up was 26.7 (0.5-58.6) months, 79.8% were men, the median age was 47.1 (21.4-80.5) years, 26.2% had AIDS and 38.8% were positive for hepatitis C virus. At baseline, the median CD4 count was 246 cells/mm(3) in naive patients and 393 cells/mm(3) in experienced patients and the median VL was 4.80 and <1.59 log copies/mL, respectively. At week 48, 81.8% of naive patients and 84.2% of experienced patients receiving the regimen reached a VL <40 copies/mL, whereas at 96 weeks this occurred in 90.5% and 92.8%, respectively. CD4 cell count increases at 48 and 96 weeks were +176.5 and +283.5 cells/mm(3) in naive patients and +74.9 and +93 cells/mm(3) in experienced patients, respectively. Overall, 86 (47%) patients discontinued the study regimen, in many cases possibly related to non-medical reasons, such as drug switches to reduce cost or changes in address due to economic constraints. Three patients died of causes unrelated to therapy and 19 (10.4%) discontinued the regimen due to adverse events.. In our cohort, abacavir/lamivudine + darunavir/ritonavir was safe, well tolerated and achieved high rates of virological suppression. In a proportion of patients, discontinuation of this effective regimen was possibly due to non-medical reasons.

Topics: Adult; Aged; Aged, 80 and over; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Cohort Studies; Darunavir; Dideoxynucleosides; Drug Combinations; Female; HIV Infections; HIV-1; Humans; Lamivudine; Male; Middle Aged; Retrospective Studies; Ritonavir; Spain; Sulfonamides; Treatment Outcome; Viral Load; Young Adult

The efficacy and safety of fixed-dose abacavir/lamivudine against tenofovir/emtricitabine, both with once-daily darunavir/ritonavir, was examined in 80 treatment-naïve patients with a baseline HIV-1 viral load of more than 100 000 copies/ml. The time to virologic failure by 48 weeks was not different between the two groups. The percentage of patients with viral suppression was not significantly different with per protocol population. Tenofovir/emtricitabine showed better tolerability; more patients on abacavir/lamivudine changed regimen than those on tenofovir/emtricitabine. A randomized trial to elucidate the efficacy and safety of these two regimens is warranted.

Topics: Adenine; Anti-HIV Agents; Darunavir; Deoxycytidine; Dideoxynucleosides; Drug Combinations; Drug Therapy, Combination; Emtricitabine; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Lamivudine; Organophosphonates; Ritonavir; Sulfonamides; Tenofovir; Viral Load

The efficacy and safety of once-daily darunavir/ritonavir and fixed-dose abacavir/lamivudine was examined in 22 treatment-naïve patients with HIV-1 infection. Three patients discontinued antiretroviral therapy due to mild adverse events. Among 18 patients who continued therapy, 66.7% had viral load less than 50 copies/ml at week 48. Only two patients experienced virologic failure with the emergence of resistant virus. This pilot study demonstrated the viral efficacy and safety of darunavir/ritonavir and abacavir/lamivudine.

Topics: Adult; Darunavir; Dideoxynucleosides; Drug Combinations; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Lamivudine; Male; Pilot Projects; Retrospective Studies; Ritonavir; Sulfonamides; Treatment Outcome; Viral Load

To investigate the feasibility and pharmacokinetics of a once-daily regimen of 2000 mg saquinavir mesylate boosted with 100 mg ritonavir.. Patients successfully treated with 1000 mg saquinavir boosted with 100 mg ritonavir twice daily together with two nucleoside or nucleotide reverse transcriptase inhibitors [N(t)RTIs] who were switched to 2000 mg saquinavir with 100 mg ritonavir once daily with unchanged N(t)RTI therapy were analysed. CD4 cells, HIV-RNA PCR and metabolic parameters were compared between baseline and 3, 6, 9 and 12 months after the switch. Saquinavir and ritonavir drug levels were measured before and a median of 3 weeks after switching from twice to once daily at 0, 1, 2, 4, 6, 9, 12 and 24 h after intake of the medication. The area under the serum concentration-time curve from 0 to 24 h (AUC(0-24)) was calculated using the trapezoidal rule.. Eighteen patients (16 males, median age of 41 years) with a median CD4 cell count of 464 cells/mm(3) were analysed. HIV-RNA PCR remained <500 copies/mL for all patients. After switching from 100 mg twice daily to 100 mg once daily, the AUC(0-24) for ritonavir decreased significantly [21 874 to 10 267 ng.h/mL, geometric mean ratio (GMR) = 0.47; P < 0.001], whereas the AUC(0-24) for saquinavir decreased only marginally from 35 000 to 34 490 ng.h/mL (GMR = 0.99; P = 0.426). The CD4 cell count and the fasting metabolic parameters remained unchanged.. Once-daily treatment with ritonavir-boosted saquinavir was well tolerated and resulted in similar saquinavir drug exposure despite much lower ritonavir concentrations when compared with a twice-daily dosing schedule.

Topics: Adenine; Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Area Under Curve; CD4 Lymphocyte Count; Deoxycytidine; Dideoxynucleosides; Drug Combinations; Emtricitabine; Female; HIV Infections; HIV-1; Humans; Lamivudine; Male; Middle Aged; Organophosphonates; Plasma; Ritonavir; RNA, Viral; Saquinavir; Tenofovir; Treatment Outcome; Viral Load