abacavir--lamivudine-drug-combination and Drug-Related-Side-Effects-and-Adverse-Reactions

There are 2 once-daily, fixed-dose-combination, dual-nucleoside analogue tablets: tenofovir 300 mg-emtricitabine 200 mg (TDF-FTC) and abacavir 600 mg-lamivudine 300 mg (ABC-3TC). Which fixed-dose-combination tablet is more effective and safe is uncertain.. We compared TDF-FTC and ABC-3TC in a randomized, open-label, 96-week trial in which either fixed-dose-combination was substituted for current nucleoside treatments in human leukocyte antigen-B*5701-negative adults with human immunodeficiency virus loads <50 copies/mL. The primary end point was virological failure (consecutive viral load measurements >400 copies/mL, by intention-to-treat). Secondary end points included death, AIDS, adverse events, serious non-AIDS events, metabolic parameters, and body composition. We used exact statistics for differences in proportions, T tests to compare means, and Cox regression for hazard ratios.. Of 441 patients who were screened, 357 were treated; 98% were men, the mean age was 45 years, 30% were receiving TDF, 20% were receiving ABC, and 24% were receiving a protease inhibitor. Virological failure was uncommon (5.6% for ABC-3TC and 3.9% for TDF-FTC; difference, 1.7%; 95% confidence interval [CI], -2.8% to 6.1%; P = .62). No participant developed AIDS, whereas 18 (5%) participants developed a serious non-AIDS event (rate, 2.79 events per 100 person-years; 95% CI, 1.76-4.43), of which 4 were fatal. TDF-FTC was associated with significantly fewer serious non-AIDS events than ABC-3TC (1.2 vs 4.8 events per 100 patient-years; hazard ratio [HR], 0.24; 95% CI, 0.08-0.73; P = .012), influenced mostly by a lower rate of cardiovascular events (0.3 vs 2.2 events per 100 patient-years; HR, 0.12; 95% CI, 0.02-0.98; P = .048). TDF-FTC resulted in significantly lower bone mineral density (mean difference in hip t score, 0.16; 95% CI, 0.08-0.23; P < .001) but not in more fractures.. In this population, TDF-FTC and ABC-3TC had similar virological efficacy, but ABC-3TC was associated with more serious non-AIDS events, particularly cardiovascular events. Clinical trials registration. NCT00192634 .

Topics: Adenine; Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Deoxycytidine; Dideoxynucleosides; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Emtricitabine; Female; HIV Infections; HLA-B Antigens; Humans; Lamivudine; Male; Middle Aged; Organophosphonates; Tenofovir; Treatment Outcome; Viral Load

Topics: Adult; Anti-Retroviral Agents; Dermatitis, Photoallergic; Dideoxynucleosides; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Heterocyclic Compounds, 3-Ring; Humans; Lamivudine; Male; Oxazines; Piperazines; Pyridones; Skin

Abacavir/lamivudine (ABC/3TC) is a nucleoside reverse transcriptase inhibitor used for treating human immunodeficiency viral (HIV) infections. Hypersensitivity reactions such as skin eruptions caused by ABC are well-known, but rarely occur in Asians. Raltegravir (RAL) is an integrase strand transfer inhibitor, that is now increasingly, used for treating HIV infections because it has few adverse effects. This retrospective analysis assessed the efficacy and safety of combined ABC/3TC and RAL in both treatment-naïve and -experienced Japanese patients with HIV infections. In all 11 treatment-naïve patients (100%), virological suppression to undetectable level was achieved. Liver transaminases, renal function, and serum lipid profiles showed no exacerbations up to 48 weeks of treatment. In 12 patients who were switched from previous regimens to ABC/3TC and RAL, HIV viral load was undetectable in 11 patients (91.6%), but remained detectable in 1 patient with poor adherence. Major reasons for switching regimens to ABC/3TC and RAL were hyperlipidemia and nausea. After switching, these adverse effects improved, and no new adverse effects were observed. Despite the small number of participants in this study, the results support the combination of ABC/3TC and RAL as a possible treatment choice in Japanese individuals with HIV-infection.

Topics: Adult; Anti-HIV Agents; Asian People; Dideoxynucleosides; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Female; HIV Infections; Humans; Hyperlipidemias; Kidney Function Tests; Lamivudine; Lipids; Liver Function Tests; Male; Middle Aged; Nausea; Pilot Projects; Raltegravir Potassium; Retrospective Studies; Treatment Outcome; Viral Load; Young Adult

The efficacy and safety of raltegravir (RAL) with tenofovir (TDF)/emtricitabine (FTC) have been well studied in human immunodeficiency virus (HIV)-infected patients. However, limited clinical data are available on the use of RAL with abacavir (ABC)/lamivudine (3TC) or zidovudine (ZDV)/3TC. We investigated HIV-1-infected Korean adults, including 13 antiretroviral-naïve patients and 15 antiretroviral-experienced patients, treated with RAL plus ABC/3TC or ZDV/3TC. Virological suppression was achieved in 12 of the 13 (92%) antiretroviral-naïve patients within 24 weeks and in all (100%) patients within 96 weeks. In 13 of the 15 treatment-experienced patients, ritonavir-boosted lopinavir (LPV/r) was replaced with RAL because of hyperlipidemia (n = 11) and diarrhea (n = 2). A significant decrease in median total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels was observed in these patients (P < 0.01, each). No adverse event related to RAL was observed in any of the 28 patients. The RAL plus ABC/3TC or ZDV/3TC regimens were effective and safe in antiretroviral-naïve Korean HIV-infected patients, and replacing LPV/r with RAL significantly improved lipid abnormalities in patients previously treated with regimens including LPV/r.

Topics: Adult; Aged; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Dideoxynucleosides; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Female; HIV Infections; HIV-1; Humans; Lamivudine; Lipids; Male; Middle Aged; Prospective Studies; Pyrrolidinones; Raltegravir Potassium; Republic of Korea; Retrospective Studies; Treatment Outcome; Viral Load; Young Adult; Zidovudine

Topics: Adenine; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Deoxycytidine; Dideoxynucleosides; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Emtricitabine; HIV Infections; Humans; Lamivudine; Organophosphonates; Tenofovir; Treatment Outcome