Choice of Initial Combination Antiretroviral Therapy in Individuals With HIV Infection Determinants and Outcomes
ABSTRACT BACKGROUND Current guidelines give recommendations for preferred combination antiretroviral therapy (cART). We investigated factors influencing the choice of initial cART in clinical practice and its outcome. METHODS We analyzed treatment-naive adults with human immunodeficiency virus (HIV) infection participating in the Swiss HIV Cohort Study and starting cART from January 1, 2005, through December 31, 2009. The primary end point was the choice of the initial antiretroviral regimen. Secondary end points were virologic suppression, the increase in CD4 cell counts from baseline, and treatment modification within 12 months after starting treatment. RESULTS A total of 1957 patients were analyzed. Tenofovir-emtricitabine (TDF-FTC)-efavirenz was the most frequently prescribed cART (29.9%), followed by TDF-FTC-lopinavir/r (16.9%), TDF-FTC-atazanavir/r (12.9%), zidovudine-lamivudine (ZDV-3TC)-lopinavir/r (12.8%), and abacavir/lamivudine (ABC-3TC)-efavirenz (5.7%). Differences in prescription were noted among different Swiss HIV Cohort Study sites (P < .001). In multivariate analysis, compared with TDF-FTC-efavirenz, starting TDF-FTC-lopinavir/r was associated with prior AIDS (relative risk ratio, 2.78; 95% CI, 1.78-4.35), HIV-RNA greater than 100 000 copies/mL (1.53; 1.07-2.18), and CD4 greater than 350 cells/μL (1.67; 1.04-2.70); TDF-FTC-atazanavir/r with a depressive disorder (1.77; 1.04-3.01), HIV-RNA greater than 100 000 copies/mL (1.54; 1.05-2.25), and an opiate substitution program (2.76; 1.09-7.00); and ZDV-3TC-lopinavir/r with female sex (3.89; 2.39-6.31) and CD4 cell counts greater than 350 cells/μL (4.50; 2.58-7.86). At 12 months, 1715 patients (87.6%) achieved viral load less than 50 copies/mL and CD4 cell counts increased by a median (interquartile range) of 173 (89-269) cells/μL. Virologic suppression was more likely with TDF-FTC-efavirenz, and CD4 increase was higher with ZDV-3TC-lopinavir/r. No differences in outcome were observed among Swiss HIV Cohort Study sites. CONCLUSIONS Large differences in prescription but not in outcome were observed among study sites. A trend toward individualized cART was noted suggesting that initial cART is significantly influenced by physician's preference and patient characteristics. Our study highlights the need for evidence-based data for determining the best initial regimen for different HIV-infected persons.
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ABSTRACT: INTRODUCTION:: Since 2002, the World Health Organization has recommended either nevirapine (NVP) or efavirenz (EFV) as part of first-line antiretroviral therapy. These two drugs are known to have differing toxicity profiles, but the clinical importance of these toxicities overall is not well established. METHODS:: We systematically reviewed adverse events among treatment-naïve HIV-positive adults and children receiving either NVP or EFV as part of first-line antiretroviral therapy. The primary outcome was drug discontinuation as a result of any adverse event; specific toxicities were evaluated as secondary outcomes. Point estimates and 95% confidence intervals (95% CI) were calculated and proportions and odds ratios (OR) pooled using fixed-effects meta-analysis. RESULTS:: We reviewed data on 26446 adult and 3975 chidren from 8 randomized trials and 26 prospective cohorts. Overall, adults on NVP were more than two times more likely to discontinue treatment due to any adverse event compared to patients on EFV (OR 2.2, 95%CI 1.9-2.6). Severe hepatotoxicity (OR 3.3, 95%CI 2.5-4.2), severe skin toxicity (OR 3.9, 95%CI 2.5-5.4), and severe hypersensitivity reactions (OR 2.4, 95%CI 1.9-2.9) were more likely to occur among patients on NVP. Patients receiving EFV were more likely to experience severe CNS-events (OR 3.4, 95%CI 2.1-5.4). Similar associations were seen in children. DISCUSSION:: Compared to NVP, EFV is associated with a lower frequency of severe adverse events, in particular treatment discontinuations. This finding supports a move towards efavirenz-based therapy as the preferred first-line treatment regimen for HIV treatment within a public health approach.AIDS (London, England) 01/2013; 27(9). DOI:10.1097/QAD.0b013e32835f1db0 · 6.56 Impact Factor
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ABSTRACT: Background While Brazil has had a long-standing policy of free access to antiretroviral therapy (ART) for all in need, the epidemiological impact of ART on human immunodeficiency virus (HIV) RNA suppression in this middle-income country has not been well evaluated. We estimate first-line ART effectiveness in a large Brazilian cohort and examine the socio-demographic, behavioral, clinical and structural factors associated with virologic suppression. Methods Virologic suppression on first-line ART at 6, 12, and 24 months from start of ART was defined as having a viral load measurement ≤400 copies/mL without drug class modification and/or discontinuation. Drug class modification and/or discontinuation were defined based on the class of a particular drug. Quasi-Poisson regression was used to quantify the association of factors with virologic suppression. Results From January 2000 through June 2010, 1311 patients started first-line ART; 987 (75%) patients used NNRTI-based regimens. Virologic suppression was achieved by 77%, 76% and 68% of patients at 6, 12 and 24 months, respectively. Factors associated with virologic suppression at 12 months were: >8 years of formal education (compared to <4 years, risk ratio (RR) 1.13, 95% confidence interval (95% CI) 1.03-1.24), starting ART in 2005-2010 (compared to 2000-2004, RR 1.25 95% CI 1.15-1.35), and clinical trial participation (compared to no participation, RR 1.08 95% CI 1.01-1.16). Also at 12 months, women showed less virologic suppression compared to heterosexual men (RR 0.90 95% CI 0.82-0.99). For the 24-month endpoint, in addition to higher education, starting ART in the later period, and clinical trial participation, older age and an NNRTI-based regimen were also independently associated with virologic suppression. Conclusions Our results show that in Brazil, a middle-income country with free access to treatment, over three-quarters of patients receiving routine care reached virologic suppression on first-line ART by the end of the first year. Higher education, more recent ART initiation and clinical trial participation were associated with improved outcomes both for the 12-month and the 24-month endpoints, suggesting that further studies are needed to understand what aspects relating to these factors lead to higher virologic suppression.AIDS Research and Therapy 09/2014; 11:29. DOI:10.1186/1742-6405-11-29 · 1.84 Impact Factor
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ABSTRACT: Clinically relevant drug–drug interactions (DDIs) refer to the pharmacological or clinical response to the administration or co-exposure of a drug with another drug that modifies the patient's response. Treatment regimens, which include agents that are involved in the cytochrome P450 (CYP450) enzyme system and transporter systems, such as P-glycoprotein may be associated with higher risk of clinically significant drug interactions. In addition, potential DDIs increase with the increasing number of concomitant drugs. HIV positive cancer patients who receive concomitant chemotherapy and combination antiretroviral therapy (cART) may achieve better response rates and higher rates of survival than those who receive chemotherapy alone, but they may be at increased risk of drug interactions. DDIs in HIV positive cancer patients receiving concomitant chemotherapy and cART may increase or decrease antineoplastic drug concentrations, potentially resulting in life threatening interactions, increased toxicity or loss of efficacy. Avoiding and managing potential interactions between cART and antineoplastic agents is an increasingly important challenge. Based on the current literature, more safety and pharmacokinetic studies are needed with the aim to document a clear survival benefit for patients undergoing chemotherapy and concomitant or sequential administration of cART.Biomedecine [?] Pharmacotherapy 06/2014; 68(5). DOI:10.1016/j.biopha.2014.04.010 · 2.11 Impact Factor