Virologic, Immunologic, Clinical, Safety, and Resistance Outcomes from a Long-Term Comparison of Efavirenz-Based Versus Nevirapine-Based Antiretroviral Regimens as Initial Therapy in HIV-1—Infected Persons

Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
HIV Clinical Trials (Impact Factor: 2.63). 09/2008; 9(5):324-36. DOI: 10.1310/hct0905-324
Source: PubMed


To compare long-term virologic, immunologic, and clinical outcomes in antiretroviral-naïve persons starting efavirenz (EFV)- versus nevirapine (NVP)-based regimens.
The FIRST study randomized patients into three strategy arms: PI+NRTI, NNRTI+NRTI, and PI+NNRTI+NRTI. NNRTI was determined by optional randomization (NVP or EFV) or by choice. For this randomized substudy, the primary endpoint was HIV RNA >50 copies/mL after 8 months or death. Genotypic resistance testing was done at virologic failure (VF; HIV RNA >1,000 copies/mL at or after 4 months).
228 persons (111 randomized to EFV, 117 to NVP) were followed for median 5 years. Rates per 100 person years for the primary endpoint were 41.2 (EFV) and 42.8 (NVP; p = .59). The percent of persons with HIV RNA <50 copies/mL was similar throughout follow-up (p = .24), as were average increases in CD4+ cells (p = .30). 423 persons declining the substudy chose EFV; 264 chose NVP. There were 915 persons in the combined cohort (randomized and choice). In the combined cohort, the risk of VF and VF with any NNRTI or NRTI resistance or resistance of any class was significantly less for EFV compared to NVP.
EFV-based regimens as initial therapy resulted in a lower risk of VF and VF with resistance than did NVP-based regimens, although immunologic and clinical outcomes were similar.

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Available from: Richard M Novak, Jan 04, 2016
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    • "A number of advancements have been made to ART in the past decade. For example, the introduction of TDF has provided another safe and efficacious alternative to d4T [16], [17]; the availability of once-daily EFV has provided a more convenient alternative to twice daily NVP that induces less NNRTI resistance [18]; and the development of boosted PIs has allowed smaller, less frequent PI doses that offer improved safety, convenience and efficacy.[19]–[21] Additionally, improvements in general HIV care have been strongly encouraged, particularly in resource-limited settings. "
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    ABSTRACT: Background Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes. Methods Patients in the TREAT Asia HIV Observational Database receiving first-line ART for ≥6 months were included. Predictors of treatment failure and treatment modification were assessed. Results Data from 4662 eligible patients was analysed. Patients started ART in 2003–2006 (n = 1419), 2007–2010 (n = 2690) and 2011–2013 (n = 553). During the observation period, tenofovir, zidovudine and abacavir use largely replaced stavudine. Stavudine was prescribed to 5.8% of ART starters in 2012/13. Efavirenz use increased at the expense of nevirapine, although both continue to be used extensively (47.5% and 34.5% of patients in 2012/13, respectively). Protease inhibitor use dropped after 2004. The rate of treatment failure or modification declined over time (22.1 [95%CI 20.7–23.5] events per 100 patient/years in 2003–2006, 15.8 [14.9–16.8] in 2007–2010, and 11.6 [9.4–14.2] in 2011–2013). Adjustment for ART regimen had little impact on the temporal decline in treatment failure rates but substantially attenuated the temporal decline in rates of modification due to adverse event. In the final multivariate model, treatment modification due to adverse event was significantly predicted by earlier period of ART initiation (hazard ratio 0.52 [95%CI 0.33–0.81], p = 0.004 for 2011–2013 versus 2003–2006), older age (1.56 [1.19–2.04], p = 0.001 for ≥50 years versus <30years), female sex (1.29 [1.11–1.50], p = 0.001 versus male), positive hepatitis C status (1.33 [1.06–1.66], p = 0.013 versus negative), and ART regimen (11.36 [6.28–20.54], p<0.001 for stavudine-based regimens versus tenofovir-based). Conclusions The observed trends in first-line ART use in Asia reflect changes in drug availability, global treatment recommendations and prescriber preferences over the past decade. These changes have contributed to a declining rate of treatment modification due to adverse event, but not to reductions in treatment failure.
    Full-text · Article · Sep 2014 · PLoS ONE
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    • "In line with previous reports our results further indicated that there was no significant difference in mean CD4 count [35] and mean viral load [36,37] in those treated with NVP-based and EFV-based regimens, in contrast to another report [38] that showed a better outcome with Efavirenz-based ART compared with Nevirapine. The lower mean immuno-hematologic parameters seen in participants from the NW when compared with those from the SW region was probably because most of the HIV/TB co-infected patients were from the NW region. "
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    ABSTRACT: Contemporary data on the immunologic, haematologic and virologic responses and predictors of virologic failure after initiation of free antiretroviral treatment in Cameroon are needed to evaluate the current treatment-monitoring algorithm and to complement efforts to scale-up and improve on the management of HIV infections. This was a cross-sectional study conducted between October 2010 and June 2012. A total of 951 participants aged 18-74 years were recruited from selected approved HIV treatment centres of the Northwest and Southwest regions. This comprised 247 males and 704 females. Demographic, self-reported risk behaviours and socioeconomic data were obtained using a structured questionnaire. Full blood and CD4 + T-cell counts were done using standard automated techniques. Determination of viral load (VL) was done using Abbott RealTime HIV-1 m2000TM system. Data was analysed using SPSS version 17. The statistical significance level was P < 0.05. The median duration of antiretroviral therapy (ART) was 24 months. The population mean CD4 + T-cell count was 255.3 cells/muL [95% CI, 236.8 - 273.9]. Overall, 45.9%, 43.8% and 10.2% of the participants had CD4 + T-cell counts of < 200 cells/muL, 200-499 cells/muL and > 500 cells/muL respectively. Anaemia was present in 26.2% of the participants with 62.3%, 25.7% and 12% described as mild, moderate and severe anaemia respectively. Virologic failure occurred in 23.2% of the participants with 12.3% having VL > 10,000 RNA copies/mL. Meanwhile 76.8% of patients attained adequate viral suppression with 40.8% having undetectable viral load. The age group 18-29 years (p = 0.024), co-infection with tuberculosis (p = 0.014), anaemia (p = 0.028) and distance from the treatment centre (p = 0.011) independently predicted virologic failure. The majority of the participants achieved adequate viral suppression after >= 6 months of ART. Despite these favourable immuno-haematologic and virologic outcomes, the National AIDS Control Program should step-up efforts to improve on antiretroviral drug distribution, as well as proper assessment and management of anaemia, foster early diagnosis and treatment of tuberculosis and enhance treatment adherence counselling especially in younger patients.
    Full-text · Article · Jan 2014 · Infectious Diseases of Poverty
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    • "This finding has been documented in similar studies. In the FIRST STUDY [24] by Berg-Wolf et al., the incidence of virological failure in an efavirenz based arm was 41.2 compared to 42.8 in the nevirapine arm per 100 person years after a follow up median time of 5 years. Implying that a NVP based regimen arm was associated with earlier virological failure compared to efavirenz, like our study finding. "
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    ABSTRACT: Early recognition of antiretroviral therapy (ART) failure in resource limited settings is a challenge given the limited laboratory facilities and trained personnel. This study aimed at describing the incidence, risk factors and the resistance associated mutations (RAMs) of first line treatment failure among HIV-1-infected children attending the Joint Clinical Research Centre (JCRC), Kampala, Uganda. A retrospective cohort of 701 children who had been initiated on ART between January 2004 and September 2009 at the JCRC was studied. Data of children aged 6 months up to 18 years who had been started on ART for at least 6 months was extracted from the clinic charts. The children who failed the first-line ART were taken as cases and those who did not fail as the controls. Data was analysed using STATA version10. Of 701 children, 240(34%) failed on first line ART (cases) and 461(66%) did not fail (controls). The overall median time (IQR) to first line ART failure was 26.4 (18.9 -- 39.1) months. The factors associated with treatment failure were poor adherence [(OR = 10, 95 CI: 6.4 -- 16.7) p < 0.001], exposure to single dose nevirapine (sdNVP) [(OR = 4.2, 95%CI:1.8-9.4), p = 0.005] and a NVP containing regimen [(OR = 2.2,95%CI:1.4-3.6), p < 0.001]. Of 109 genotypic resistance profiles analyzed, the commonest non nucleoside reverse transcriptase inhibitor (NNRTI) resistance associated mutations (RAM) were: K103N (59; 54%)), Y181C (36; 27%)) and G190A (26; 24%)) while the commonest nucleoside reverse transcriptase inhibitor (NRTI) RAM was the M184V (89; 81%). Thymidine analogue- mutations (TAMs) were detected in 20% of patients. One in three children on first-line ART are likely to develop virological treatment failure after the first 24 months of therapy. . Poor adherence to ART, a NVP based first-line regimen, prior exposure to sdNVP were associated with treatment failure.
    Full-text · Article · Nov 2013 · AIDS Research and Therapy
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