ABSTRACT
OBJECTIVES: We describe the outcomes of second-line drug resistance profiles and predict the efficacy of drugs for third-line therapy in patients monitored without the benefit of plasma HIV-1 RNA viral load (VL) or resistance testing. METHODS: We recruited 106 HIV-1-infected patients after second-line treatment failure in Mali. VL was determined by the Abbott RealTime system and the resistance by the ViroSeq HIV-1 genotyping system. The resistance testing was interpreted using the latest version of the Stanford algorithm. RESULTS: Among the 106 patients, 93 had isolates successfully sequenced. The median age, VL and CD4 cells were respectively 35 years, 72â000 copies/mL and 146 cells/mm(3). Patients were exposed to a median of 4 years of treatment and to six antiretrovirals. We found 20% of wild-type viruses. Resistance to etravirine was noted in 38%, to lopinavir in 25% and to darunavir in 12%. The duration of prior nucleos(t)ide reverse transcriptase inhibitor exposure was associated with resistance to abacavir (Pâ<â0.0001) and tenofovir (Pâ=â0.0001), and duration of prior protease inhibitor treatment with resistance to lopinavir (Pâ<â0.0001) and darunavir (Pâ=â0.06). CONCLUSION: Long duration of therapy prior to failure was associated with high levels of resistance and is directly related to limited access to VL monitoring and delayed switches to second-line treatment, precluding efficacy of drugs for third-line therapy. This study underlines the need for governments and public health organizations to recommend the use of VL monitoring and also the availability of darunavir and raltegravir for third-line therapies in the context of limited-resource settings.
Subject(s)
Anti-Retroviral Agents/pharmacology , Anti-Retroviral Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , Drug Resistance, Viral , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/drug effects , Adult , Drug Monitoring , Female , HIV-1/isolation & purification , Humans , Male , Mali , Middle Aged , Treatment Failure , Viral Load , Young AdultABSTRACT
Mutations in the connection domain (CD) of reverse transcriptase have been implicated in reverse transcriptase inhibitor (RTI) resistance, but this is controversial and little is known in non-B subtype HIV-1. We determined CD mutations prevalence in a population infected predominantly with CRF02_AG and investigated associations with phenotypic RTI resistance. Detected CD mutations were G335D (82.3%), A371V (69.8%), E399D (9.4%), N348I (5.2%), V365I (4.2), Y318F (2.1%), G333E (2.1%), and A360V (2.1%). Mutations were largely polymorphic and did not confer RTI resistance. The observed trend toward reduced likelihood of etravirine or nevirapine resistance in the presence of G335D should be investigated further.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Reverse Transcriptase/genetics , Alkynes , Benzoxazines/pharmacology , Benzoxazines/therapeutic use , Binding Sites/drug effects , Binding Sites/genetics , Cyclopropanes , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Drug Resistance, Viral/genetics , Emtricitabine , HIV Infections/virology , HIV Reverse Transcriptase/antagonists & inhibitors , HIV-1/drug effects , HIV-1/enzymology , HIV-1/genetics , Humans , Mali , Mutation/genetics , Nevirapine/pharmacology , Nevirapine/therapeutic use , Phenotype , Treatment FailureABSTRACT
AIM: To investigate the association between alcohol use and adherence to highly active antiretroviral treatment (HAART) among human immunodeficiency virus (HIV)-infected patients in sub-Saharan Africa. DESIGN AND SETTING: Cross-sectional survey conducted in eight adult HIV treatment centres from Benin, Côte d'Ivoire and Mali. Participants and measurements During a 4-week period, health workers administered the Alcohol Use Disorders Identification Test to HAART-treated patients and assessed treatment adherence using the AIDS Clinical Trials Group follow-up questionnaire. FINDINGS: A total of 2920 patients were enrolled with a median age of 38 years [interquartile range (IQR) 32-45 years] and a median duration on HAART of 3 years (IQR 1-4 years). Overall, 91.8% of patients were identified as adherent to HAART. Non-adherence was associated with current drinking [odds ratio (OR) 1.4; 95% confidence interval (CI) 1.1-2.0], hazardous drinking (OR 4.7; 95% CI 2.6-8.6) and was associated inversely with a history of counselling on adherence (OR 0.7; 95% CI 0.5-0.9). CONCLUSIONS: Alcohol consumption and hazardous drinking is associated with non-adherence to HAART among HIV-infected patients from West Africa. Adult HIV care programmes should integrate programmes to reduce hazardous and harmful drinking.
