title: Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India.
abstract: The free antiretroviral therapy (ART) program in India has scaled up to register second largest number of people living with HIV/AIDS across the globe. To assess the effectiveness of current first-line regimen we estimated virological suppression on completion of 1 year of ART. The study describes the correlates of virological failure (VF) and multinucleoside reverse transcriptase inhibitor (NRTI) drug resistance mutations (DRMs).In this cross-sectional study conducted between June and August 2014, consecutive adults from 4 State sponsored ART clinics of western India were recruited for plasma viral load screening at 12 ± 2 months of ART initiation. Individuals with plasma viral load >1000 copies/mL were selected for HIV drug resistance (HIVDR) genotyping. Logistic regression analyses were performed to assess factors associated with VF and multi-NRTI resistance mutations. Criteria adopted for multi-NRTI resistance mutation were either presence of K65R or 3 or more thymidine analog mutations (TAMs) or presence of M184V along with 2 TAMs.Of the 844 study participants, virological suppression at 1 year was achieved in 87.7% of individuals. Factors significantly associated with VF (P < 0.005) were 12 months CD4 count of ≤100 cells/μL (adjusted OR -7.11), low reported adherence (adjusted OR -4.44), and those living without any partner (adjusted OR -1.98). In patients with VF, the prevalence of non-nucleoside reverse transcriptase inhibitor (NNRTI) DRM (78.75%) were higher as compared to NRTI (58.75%). Multi-NRTI DRMs were present in 32.5% of sequences and were significantly associated with CD4 count of ≤100 cells/μL at baseline (adjusted OR -13.00) and TDF-based failing regimen (adjusted OR -20.43). Additionally, low reported adherence was negatively associated with multi-NRTI resistance (adjusted OR -0.11, P = 0.015). K65R mutation was significantly associated with tenofovir (TDF)-based failing regimen (P < 0.001).The study supports early linkage of HIV-infected individuals to the program for ART initiation, adherence improvement, and introduction of viral load monitoring. With recent introduction of TDF-based regimen, the emergence of K65R needs to be monitored closely among HIV-1 subtype C-infected Indian population.
authors.affiliation: HIV Drug Resistance Laboratory Department of Clinical Sciences, National AIDS Research Institute Department of Medicine, BJ Medical College and Sasoon General Hospital, Pune Department of Medicine, Command Hospital (Air Force), Bangalore Department of Tuberculosis and Chest Diseases, YCM Hospital Department of Epidemiology and Biostatistics Department of Molecular Virology Department of Immunology, National AIDS Research Institute, Pune Department of AIDS Control, National AIDS Control Organization, New Delhi, India.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Karade
authors.forename: Manisha V
authors.initials: MV
authors.lastname: Ghate
authors.forename: Devidas N
authors.initials: DN
authors.lastname: Chaturbhuj
authors.forename: Dileep B
authors.initials: DB
authors.lastname: Kadam
authors.forename: Subramanian
authors.initials: S
authors.lastname: Shankar
authors.forename: Nitin
authors.initials: N
authors.lastname: Gaikwad
authors.forename: Shraddha
authors.initials: S
authors.lastname: Gurav
authors.forename: Rajneesh
authors.initials: R
authors.lastname: Joshi
authors.forename: Suvarna S
authors.initials: SS
authors.lastname: Sane
authors.forename: Smita S
authors.initials: SS
authors.lastname: Kulkarni
authors.forename: Swarali N
authors.initials: SN
authors.lastname: Kurle
authors.forename: Ramesh S
authors.initials: RS
authors.lastname: Paranjape
authors.forename: Bharat B
authors.initials: BB
authors.lastname: Rewari
authors.forename: Raman R
authors.initials: RR
authors.lastname: Gangakhedkar
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D060005:Genotyping Techniques; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors; D017211:Treatment Failure
chemical_list: D018894:Reverse Transcriptase Inhibitors