Brief Report: CYP2B6 516G>T Minor Allele Protective of Late Virologic Failure in Efavirenz-Treated HIV-Infected Patients in Botswana

Abstract

Background CYPB2B6 polymorphisms that affect efavirenz (EFV) concentrations are common, but the effect of this polymorphism on HIV virologic failure in clinical practice settings has not fully been elucidated. Our objective was to investigate the relationship between the CYPB2B6 516G>T genotype and late virologic failure in patients treated with EFV in Gaborone, Botswana. Setting We performed a case-control study that included 1,338 HIV-infected black Batswana on EFV-based antiretroviral therapy (ART). Patients were approached for enrollment during regular visits at one of the outpatient HIV clinics between 7/2013-4/2014. Methods Cases experienced late HIV failure, defined as plasma HIV RNA >1000 copies/mL after maintaining viral suppression (<400 copies/mL) for at least 6 months. For each case, a total of 4 control patients were randomly sampled from the same population. Controls had plasma HIV RNA <400 copies/mL on ART for at least 6 months. Logistic regression was used to determine the adjusted odds of late HIV failure by 516G>T genotype. Results After adjustment for the confounding variables age and CD4 count, the CYPB2B6 516 T-allele was protective against late HIV virologic breakthrough, adjusted OR 0.70; 95%CI 0.50-0.97. Conclusion The CYPB2B6 516 T-allele was protective against late virologic breakthrough in patients with initial (6 month) HIV RNA suppression on EFV-based ART. Future studies are needed to assess long-term viral benefits of identifying and offering EFV containing ART to black African HIV-infected patients with CYPB2B6 T-alleles, especially given the wider availability of a single pill EFV in this setting.

Association of CYP2B6 Genetic Variation with Efavirenz and Nevirapine Drug Resistance in HIV-1 Patients from Botswana

“…Pharmacogenetic studies of EFV and NVP have mostly been based on the CYP2B6 516G>T and 983T>C SNPs, with little or no clear assessment of the impact of the CYP2B6 785A>G and −82T>C SNPs. 14 Studies from Botswana on HIV patients taking EFV-based ART showed that the CYP2B6 516T allele was protective against 1-year, 29 but not at 6-months, 30 virologic breakthrough. However, no HIV DRMs have been assessed in either study.…”

Polymorphisms in cytochrome P450 are associated with extensive efavirenz pharmacokinetics and CNS toxicities in an HIV cohort in Botswana

“…Also, the current study is restricted to an average follow-up time of 6 months, and so questions regarding the impact of these polymorphisms in the response to therapeutic drugs and the long-term virologic and immunological response in this population remain to be answered. However, in a follow-up study in Botswana we observed that the CYP2B6 516G>T polymorphism showed a protective association with regards to the maintenance of HIV suppression [ 14 ]. Finally, in this exploratory analysis evaluating a total of 21 SNPs we cannot exclude that these findings were not due to chance and therefore future replication is essential to establish the validity of these findings.…”

Two-way mobile phone intervention compared with standard-of-care adherence support after second-line antiretroviral therapy failure: a multinational, randomised controlled trial

“…Although two-way messaging has been shown to be effective in treatment-naive individuals, treatment-experienced individuals pose a potentially greater challenge. Although treatment failure can be due to drug stockouts, 12 drug-drug interactions, 13 drug metabolism, 14,15 and pre-existing viral resistance, 16,17 populations with repeated treatment failures are likely to have a high number of individuals with repeated non-adherence. 18 Therefore, we aimed to find out if an intervention consisting of a two-way messaging system, with offers of local adherence support for individuals who requested help or who were not engaged with the system, would result in better HIV treatment outcomes than standard- of-care adherence support.…”