Treatment Outcomes of Recommended First-Line Antiretroviral Regimens in Resource-Limited Clinics

Institute of Human Virology, Clinical Division, Baltimore, MD 21201, USA.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 02/2012; 60(3):314-20. DOI: 10.1097/QAI.0b013e31824e5256
Source: PubMed


Although used globally, little data exist on the efficacy of nevirapine (NVP) used in combination with tenofovir (TDF)/emtricitabine or lamivudine (XTC), and no large randomized prospective control trials exists comparing this combination with efavirenz (EFV)/TDF/(XTC).
As part of the AIDSRelief program, a retrospective review of patient medical chart information along with a cross-sectional viral load, and adherence measurement was conducted between 2004 and 2009. An on-treatment analysis excluded patients who died, transferred out of care, or were lost to follow-up. A switch of antiretrovirals for any reason was considered a failure in the intent-to-treat analysis. Patients with only clinically relevant reasons for switching such as toxicity, adverse effects, viral failure or clinical/immunological failure, lost to follow-up, and death were considered failures as part of the modified-intent-to-treat analysis. Step-wise multiple regression analysis was used to identify variables that were associated with viral suppression.
A random sample of 3862 patients met criteria and were included in this analysis. In the on-treatment analysis, older age (P < 0.004) and baseline CD4 <100 cells per cubic millimeter (P < 0.021) were the most significant variables impacting viral load. Patients on TDF/XTC/EFV achieved higher rates of viral suppression compared with patients on TDF/XTC/NVP or azidothymidine (AZT)/lamivudine (3TC)/NVP.
Our data show that patients on TDF/XTC/EFV had better outcomes than patients on TDF/XTC/NVP, AZT/3TC/EFV, or AZT/3TC/NVP. High rates of virologic suppression seen in patients on this regimen are consistent with previous studies and indicate the need to increase use of this regimen in HIV programs to promote sustainable viral suppression over time.

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    • "We also found older age (≥40 years) [17] and more years of schooling to be associated with increased odds of having an undetectable viral load. This may be attributable to increasing levels of medication non-adherence among younger and less educated patients. "
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    ABSTRACT: Background Previous cohort studies have demonstrated the beneficial effects of antiretroviral therapy (ART) on viral load suppression. We aimed to examine the factors associated with virologic suppression for HIV-infected patients on ART receiving care at the Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Methods HIV-1 RNA levels and CD4+ T-cell counts at the date closest to midyear (1 July) were evaluated for 1,678 ART-naïve patients ≥18 years of age initiating ART between 1997 and 2010. The odds ratios (OR) and 95% confidence intervals (CI) for having an undetectable viral load (≤400 copies/mL) were estimated using generalized estimating equations regression models adjusted for clinical and demographic factors. Time-updated covariates included age, years since HIV diagnosis, hepatitis C diagnosis and ART interruptions. Results Between 1997 and 2011, the proportion of patients with an undetectable viral load increased from 6% to 78% and the median [interquartile range] CD4+ T-cell count increased from 207 [162, 343] to 554 [382, 743] cells/μL. Pre-treatment median CD4+ T-cell count significantly increased over the observation period from 114 [37, 161] to 237 [76, 333] cells/μL (p < .001). The per-year adjusted OR (aOR) for having undetectable viral load was 1.18 (95% CI = 1.16-1.21). ART interruptions >1 month per calendar significantly decreased the odds [aOR = 0.32 (95% CI = 0.27-0.38)] of having an undetectable viral load. Patients initiating on a protease inhibitor (PI)-based first-line regimen were less likely to have undetectable viral load [aOR = 0.72 (95% CI = 0.63-0.83)] compared to those initiating on a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. Conclusions Our results demonstrate significant improvements in virologic outcomes from 1997 to 2011, which persisted after adjusting for other factors. This may in part be due to improvements in care and new treatment options. NNRTI- versus PI-based first-line regimens were found to be associated with increased odds of having an undetectable viral load, consistent with previous studies. Treatment interruptions were found to be the most important determinant of not having an undetectable viral load. Studies are needed to characterize the reasons for treatment interruptions and to develop subsequent strategies for improving adherence to ART.
    BMC Infectious Diseases 06/2014; 14(1):322. DOI:10.1186/1471-2334-14-322 · 2.61 Impact Factor
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    • "Retrospective Cohorts Study and Cohort Setting and Total patients in Cohort Nevirapine ( NVP ) Efavirenz ( EFV ) Time point of analysis ( weeks ) Virologic outcome definition Median Age Female % Median Baseline CD4 cells / mm3 Median Baseline viral load copies / ml or log10c / ml % with AIDS or CDC / C Total on NVP Median Age Female % Median Baseline CD4 cells / mm3 Median Baseline viral load copies / ml or log10c / ml AIDS or CDC / C% Total on EFV Manosuthi et al ( 2008 ) [ 24 ] 2 Thailand ( n = 188 ) 35 26% 36 5 , 7 – 111 36 30% 36 5 , 6 – 77 @24 VS , 50 Amoroso et al ( 2012 ) "
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    ABSTRACT: There is conflicting evidence and practice regarding the use of the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) and nevirapine (NVP) in first-line antiretroviral therapy (ART). We systematically reviewed virological outcomes in HIV-1 infected, treatment-naive patients on regimens containing EFV versus NVP from randomised trials and observational cohort studies. Data sources include PubMed, Embase, the Cochrane Central Register of Controlled Trials and conference proceedings of the International AIDS Society, Conference on Retroviruses and Opportunistic Infections, between 1996 to May 2013. Relative risks (RR) and 95% confidence intervals were synthesized using random-effects meta-analysis. Heterogeneity was assessed using the I(2) statistic, and subgroup analyses performed to assess the potential influence of study design, duration of follow up, location, and tuberculosis treatment. Sensitivity analyses explored the potential influence of different dosages of NVP and different viral load thresholds. Of 5011 citations retrieved, 38 reports of studies comprising 114 391 patients were included for review. EFV was significantly less likely than NVP to lead to virologic failure in both trials (RR 0.85 [0.73-0.99] I(2) = 0%) and observational studies (RR 0.65 [0.59-0.71] I(2) = 54%). EFV was more likely to achieve virologic success than NVP, though marginally significant, in both randomised controlled trials (RR 1.04 [1.00-1.08] I(2) = 0%) and observational studies (RR 1.06 [1.00-1.12] I(2) = 68%). EFV-based first line ART is significantly less likely to lead to virologic failure compared to NVP-based ART. This finding supports the use of EFV as the preferred NNRTI in first-line treatment regimen for HIV treatment, particularly in resource limited settings.
    PLoS ONE 07/2013; 8(7):e68995. DOI:10.1371/journal.pone.0068995 · 3.23 Impact Factor
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    ABSTRACT: Introduction: Since 2002, the WHO 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 risk of these toxicities overall is not well established. Methods: We systematically reviewed adverse events among treatment-naive 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% CIs) were calculated and proportions and odds ratios (ORs) pooled using fixed-effects meta-analysis. Results: We reviewed data on 26,446 adults and 3975 children from eight 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 central nervous system 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 toward EFV-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 · 5.55 Impact Factor
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