abacavir--lamivudine-drug-combination and fosamprenavir

The human immunodeficiency virus (HIV) was discovered in 1982, but treatment strategies were not introduced until 5 years later. Early regimens consisted of one or two drugs and often led to treatment failure. Since the advent in 1995 of highly active antiretroviral therapy (HAART), which consists of at least three agents, a dramatic improvement has been seen in the number of patients attaining undetectable viral loads, improved CD4 counts, and improved survival. However, early HAART often consisted of drugs with complex dosing schedules, strict food requirements, treatment-limiting adverse effects, and the need to take 16-20 pills/day. These treatment barriers often led to patient nonadherence, with subsequent treatment failure and development of resistant strains. The CD4 count and viral load are the most important surrogate markers used to determine if treatment is indicated. Current guidelines suggest starting treatment in patients who are symptomatic with an acquired immunodeficiency syndrome-defining illness regardless of CD4 count or viral load, as well as in asymptomatic patients with a CD4 count of 350 cells/mm(3) or below. In patients with CD4 counts above 350 cells/mm(3) and viral loads above 100,000 copies/ml, some clinicians prefer to defer treatment, whereas others will consider starting therapy; treatment is deferred in patients with CD4 counts above 350 cells/mm(3) and viral load s below 100,000 copies/ml. If therapy is started, the selection of appropriate agents is based on comorbidities (liver disease, depression, cardiovascular disease), pregnancy status, adherence potential (dosage regimen, pill burden, dosing frequency), food restrictions (dosing with regard to meals), adverse drug effects, and potential drug-drug interactions. Within the last 8 years, newer antiretroviral agents have focused on ways to improve adherence, such as convenient dosing (fewer pills), pharmacokinetic and formulation changes to reduce dosing frequency or pill burden, and coformulated dosage forms that contain two or three drugs in one convenient pill. Other improvements include increased potency of newer agents, agents sensitive to a highly resistant virus, improved adverse-effect profile (e.g., less gastrointestinal effects, improved lipid profiles), as well as protease inhibitor boosting with ritonavir, which takes advantage of the potent cytochrome P450 inhibitory action of ritonavir. This review focuses on the concepts of antiretroviral therapy, barrier

Topics: Adenine; Animals; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Carbamates; Clinical Trials as Topic; Deoxycytidine; Dideoxynucleosides; Drug Administration Schedule; Drug Combinations; Drug Resistance, Multiple, Viral; Drug Therapy, Combination; Drugs, Investigational; Emtricitabine; Enfuvirtide; Furans; HIV Envelope Protein gp41; HIV Infections; HIV Protease Inhibitors; Humans; Lamivudine; Oligopeptides; Organophosphates; Organophosphonates; Patient Compliance; Peptide Fragments; Pyridines; Pyrones; Reverse Transcriptase Inhibitors; Sulfonamides; Tenofovir

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

The aim of the study was to assess whether pill burden is associated with self-reported adherence to current combination antiretroviral regimens and health status in a large sample of unselected and chronically treated HIV-infected patients.. An adherence and health status questionnaire was offered to all patients collecting their drugs between March and May 2010 at our clinic; both parameters were primarily evaluated using a visual analogue scale. Linear correlations were evaluated using Spearman's correlation coefficient. Wilcoxon's rank-sum test and the χ(2) test were used to compare quantitative and qualitative variables. The generalized linear model was used in multivariable analyses.. Among 2763 subjects on treatment during the study period, 2114 (78.8% male; mean age 46.9 ± 8.84 years) were tested for adherence; 1803 (85.3%) had viral loads < 50 HIV-1 RNA copies/mL. After adjusting for age, gender, HIV risk factor, current CD4 count, pill burden and dosing interval, adherence was higher in patients with undetectable HIV RNA (P < 0.0001) and directly associated with current CD4 count (P = 0.029). After adjusting for the same variables, health status was better in patients with undetectable viraemia (P = 0.004) and in men who have sex with men (MSM) and heterosexuals compared with injecting drug users and those with other risk factors (P < 0.0001 for MSM and P = 0.008 for heterosexuals); it was also directly associated with current CD4 count (P < 0.0001) and inversely associated with age (P < 0.0001) and pill burden (P = 0.019).. In this highly adherent population, the number of daily pills was related to self-reported health status but not to self-reported adherence, whereas the dosing interval did not influence self-reported adherence or health status.

Topics: Adenine; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Carbamates; CD4 Lymphocyte Count; Cross-Sectional Studies; Deoxycytidine; Dideoxynucleosides; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Furans; HIV Infections; Humans; Italy; Lamivudine; Male; Medication Adherence; Middle Aged; Nevirapine; Oligopeptides; Organophosphates; Organophosphonates; Oxazines; Pyridines; Self Report; Sulfonamides; Surveys and Questionnaires; Viral Load