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Risk Factors for Incident Diabetes in a Cohort Taking First-Line Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy.

ABSTRACT: Efavirenz is the preferred nonnucleoside reverse transcriptase inhibitor (NNRTI) in first-line antiretroviral therapy (ART) regimens in low- and middle-income countries, where the prevalence of diabetes is increasing. Randomized control trials have shown mild increases in plasma glucose in participants in the efavirenz arms, but no association has been reported with overt diabetes. We explored the association between efavirenz exposure and incident diabetes in a large Southern African cohort commencing NNRTI-based first-line ART. Our cohort included HIV-infected adults starting NNRTI-based ART in a private sector HIV disease management program from January 2002 to December 2011. Incident diabetes was identified by the initiation of diabetes treatment. Patients with prevalent diabetes were excluded. We included 56,298 patients with 113,297 patient-years of follow-up (PYFU) on first-line ART. The crude incidence of diabetes was 13.24 per 1000 PYFU. Treatment with efavirenz rather than nevirapine was associated with increased risk of developing diabetes (hazard ratio 1.27 (95% confidence interval (CI): 1.10-1.46)) in a multivariate analysis adjusting for age, sex, body mass index, baseline CD4 count, viral load, NRTI backbone, and exposure to other diabetogenic medicines. Zidovudine and stavudine exposure were also associated with an increased risk of developing diabetes. We found that treatment with efavirenz, as well as stavudine and zidovudine, increased the risk of incident diabetes. Interventions to detect and prevent diabetes should be implemented in ART programs, and use of antiretrovirals with lower risk of metabolic complications should be encouraged.

SUBMITTER: Karamchand S

PROVIDER: S-EPMC4782850 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Risk Factors for Incident Diabetes in a Cohort Taking First-Line Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy.

Karamchand Sumanth S Leisegang Rory R Schomaker Michael M Maartens Gary G Walters Lourens L Hislop Michael M Dave Joel A JA Levitt Naomi S NS Cohen Karen K

Medicine 20160301 9

Efavirenz is the preferred nonnucleoside reverse transcriptase inhibitor (NNRTI) in first-line antiretroviral therapy (ART) regimens in low- and middle-income countries, where the prevalence of diabetes is increasing. Randomized control trials have shown mild increases in plasma glucose in participants in the efavirenz arms, but no association has been reported with overt diabetes. We explored the association between efavirenz exposure and incident diabetes in a large Southern African cohort com ...[more]

PMID: 26945366

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Project description:BACKGROUND:Our aim was to study the incidence and pattern of dyslipidemia among human immunodeficiency virus (HIV)-infected patients with tuberculosis (TB) who received once-daily antiretroviral therapy (ART). METHODS:Antiretroviral-naive HIV-infected patients with TB were recruited to a trial of once-daily nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based ART and treated with rifampicin-based thrice-weekly antituberculosis treatment (ATT); participants were randomized to receive didanosine (250/400 mg) and lamivudine (300 mg) with either efavirenz (600 mg) or nevirapine (400 mg) once-daily after an intensive phase of ATT. Fasting triglyceride (TG) level, total cholesterol (TC) level, low-density cholesterol (LDL-c) level and high-density cholesterol (HDL-c) level were measured at baseline and at 6 and 12 months. Lipid levels at 6 and 12 months were compared with baseline values with use of repeated measures analyses. McNemar test was used to compare the proportion of patients with lipid abnormality at baseline versus at 12 months, and ?² test was used to compare between the 2 groups. RESULTS:Of 168 patients (79% men; mean age, 36 years; mean weight, 42 kg; median CD4+ cell count, 93 cells/mm³), 104 received efavirenz-based ART, and 64 received nevirapine-based ART. After 6 months, TC levels increased by 49 mg/dL, LDL-c levels by 30 mg/dL, and HDL-c levels increased by 18 mg/dL (P < .001 for all). At baseline and at 12 months, TC was >200 mg/dL for 1% and 26% of patients, respectively; LDL-c level was >130 mg/dL for 3% and 23%, respectively; HDL-c level was <40 mg/dL for 91% and 23%, respectively; and blood glucose level was >110 mg/dL for 14% and 13%, respectively. TC level >200 mg/dL was more common among patients who received efavirenz than among those who received nevirapine (32% vs 16%; P = .04). CONCLUSIONS:HIV-infected patients with TB who initiate NNRTI-based ART undergo complex changes in lipid profile, highlighting the importance of screening and treating other cardiovascular disease risk factors in this population.

Project description:OBJECTIVES:Among women initiating first-line nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based-ART with and without a history of single-dose nevirapine (sdNVP) with or without zidovudine with or without lamivudine (ZDV with and without 3TC) for prevention of mother-to-child HIV transmission (PMTCT), we hypothesized that pre-ART HIV-drug resistance would be associated with virologic failure DESIGN/METHODS:: In a prospectively enrolled study, three genotypic drug-resistance assays [oligonucleotide-ligation-assay (OLA), consensus sequencing, and next-generation sequencing by Illumina] were retrospectively performed to detect pre-ART drug resistance. Minority or majority drug-resistant variants identified in pre-ART RNA and/or DNA, a history of antiretrovirals for PMTCT, and other risk factors were assessed for association with virologic failure. RESULTS:Failure occurred in 38/169 (22.5%) women, and was associated with pre-ART drug resistance detected by any assay (OLA of plasma or PBMC, consensus sequencing of PBMC and/or plasma, and next-generation sequencing of PBMC at frequencies of at least 10% and as minority variants; all P?<?0.0001). Failure was also associated with PMTCT using sdNVP and ZDV with or without 3TC, but not sdNVP only; however, the longer time-interval between PMTCT and ART initiation observed for sdNVP-only women showed no interaction with failure. Viral loads and OLA of PBMC in longitudinal specimens demonstrated rapid failure and emergence of drug resistance, particularly among sdNVP and ZDV with or without 3TC-experienced women with pre-ART drug-resistant minority variants by next-generation sequencing but without drug resistance by OLA or consensus sequencing. CONCLUSION:Pre-ART drug resistance was detected similarly by OLA of PBMC or plasma and by consensus sequencing, and was associated with virologic failure soon after initiation of first-line NVP-based ART. A history of sdNVP and ZDV with or without 3TC for PMTCT or minority variants detected by next-generation sequencing identified additional women with failure. These findings emphasize the value of assessing individual antiretroviral history, particularly nonsuppressive antiretrovirals with at least two drug classes, and testing for pre-ART drug resistance, including minority variants.

Dataset Information

Risk Factors for Incident Diabetes in a Cohort Taking First-Line Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy.

Publications

Risk Factors for Incident Diabetes in a Cohort Taking First-Line Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy.

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