ABSTRACT
OBJECTIVES: We evaluated the prevalence of primary HIV drug resistance in a population of 128 injection drug users (48 female) prior to initiating antiretroviral therapy. METHODS: Genotypic and phenotypic profiles were obtained retrospectively for the period June 1996 to February 2007. Genotypic drug resistance was defined as the presence of a major mutation (IAS-USA table, 2007 revision), adding revertants at reverse transcriptase (RT) codon 215. Phenotypic drug resistance was defined as the fold change associated with >or=80% loss of the wild type virologic response due to viral resistance based on virtual phenotype analysis. RESULTS: Genotypic drug resistance was uncommon, and was only identified in six (4.7%) cases, all in the RT gene (L100I, K103N, Y181C, M184V, Y188L, and T215D). There were no cases of multi-class or protease inhibitor (PI) resistance. However, polymorphisms in the protease and RT genes were extremely common. Phenotypic drug resistance was also identified in six (4.7%) patients, four in the RT gene (in patients with mutations K103N, Y181C, M184V and Y188L) and two the protease gene (in two patients with minor PI mutations). In addition, 25 (19.5%) of the patients had reduced susceptibility to PIs, defined as resistance>20% but <80% of the wild type virologic response, with no primary PI mutations detected in all these patients. CONCLUSION: The prevalence of primary HIV drug resistance was low in this population of injection drug users.
Subject(s)
Anti-HIV Agents/pharmacology , Drug Resistance, Viral , HIV Infections/complications , HIV Infections/drug therapy , HIV-1/drug effects , Reverse Transcriptase Inhibitors/pharmacology , Substance Abuse, Intravenous/complications , Adult , Anti-HIV Agents/therapeutic use , Canada , Drug Resistance, Viral/genetics , Female , Genotype , HIV Infections/virology , HIV Protease/genetics , HIV Protease Inhibitors/pharmacology , HIV Protease Inhibitors/therapeutic use , HIV Reverse Transcriptase/genetics , HIV-1/genetics , Humans , Male , Microbial Sensitivity Tests/methods , Middle Aged , Mutation , Phenotype , Prevalence , Reverse Transcriptase Inhibitors/therapeutic useSubject(s)
Antiretroviral Therapy, Highly Active , Drug Resistance, Viral/genetics , Mutation , Patient Compliance/statistics & numerical data , Adult , CD4 Lymphocyte Count , Canada , Female , Genotype , HIV/drug effects , HIV/genetics , HIV Infections/blood , HIV Infections/drug therapy , HIV Infections/virology , Humans , Longitudinal Studies , Male , Methadone/therapeutic use , Middle Aged , Models, Theoretical , RNA, Viral/blood , RNA, Viral/genetics , Retrospective Studies , Viral LoadABSTRACT
OBJECTIVES: We have measured methadone dose adjustments and treatment responses after nevirapine (NVP)-, efavirenz (EFV)-, ritonavir-boosted lopinavir (LPV/r), or atazanavir (ATV; with or without ritonavir)-based highly active antiretroviral therapy (HAART) was initiated in injection drug users (IDUs). METHODS: We identified 120 IDUs receiving HAART and methadone within a directly observed therapy (DOT) program. Follow-up was according to clinical standards, with changes in methadone dose being made as required to achieve clinical stabilization within the first 3 months of HAART. RESULTS: The observed median methadone dose changes from baseline were 20 mg/d (P<0.001) in patients on NVP, with 32 (86%) of 37 patients requiring daily dose increases, and 7.5 mg/d (P=0.004) in patients on EFV, with 11 (61%) of 18 patients requiring daily dose increases. Conversely, median changes were 0 mg/d for patients on LPV/r (P=0.56) or ATV (P=0.95). Virologic suppression (HIV RNA<400 copies/mL) was achieved in 26 (70%) of 37, 12 (67%) of 18, 25 (76%) of 33, and 24 (75%) of 32 patients receiving NVP-, EFV-, LPV/r-, and ATV-based regimens, respectively (P=0.89). CONCLUSIONS: Although methadone-based DOT can be a successful tool for the coadministration of HAART, careful monitoring is required to ensure that methadone withdrawal does not adversely affect the goals of treatment, particularly when nonnucleoside reverse transcriptase inhibitors are used.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV-1 , Methadone/therapeutic use , Narcotics/therapeutic use , Substance Abuse, Intravenous/drug therapy , Administration, Oral , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Directly Observed Therapy , Drug Interactions , Female , HIV Infections/complications , HIV Infections/virology , HIV-1/isolation & purification , Humans , Male , Methadone/administration & dosage , Narcotics/administration & dosage , Substance Abuse, Intravenous/complications , Substance Withdrawal Syndrome/drug therapy , Substance Withdrawal Syndrome/etiology , Treatment OutcomeABSTRACT
To evaluate the impact of mutations at reverse transcriptase codon 135 on treatment outcomes in patients receiving NNRTI-based antiretroviral therapy, a total of 68 patients (30 with and 38 without baseline mutations at codon 135) were evaluated. Median increases in CD4 counts were 135 and 90 cells/mm(3) (p=0.32), virologic suppression (HIV RNA < 400 copies/mL) was achieved in 16 (53%) and 16 (42%) patients (p=0.50), while NNRTI resistance was detected in 10/14 (71%) and 16/22 (73%) in patients with and without mutations at codon 135, respectively. Patients who experienced a virologic breakthrough and had a baseline mutation at codon 135 were more likely to evolve a single NNRTI resistance mutation (8/14 vs 4/22, p=0.029) but less likely to evolve multiple NNRTI resistance mutations (2/14 vs 12/22, p = 0.033). Mutations at codon 135 do not affect response rates, but affect the pattern of development of NNRTI resistance mutations. This has important implications for the subsequent use of newer NNRTIs such as etravirine in salvage therapy.
