HIV-1 Molecular Epidemiology and Drug Resistance in India Ujjwal - PowerPoint PPT Presentation

HIV-1 Molecular Epidemiology and Drug Resistance in India Ujjwal Neogi St. John’s Medical College and Hospital, Bangalore, India II EuResist INTERNATIONAL MEETING, 6 th May 2011 Bonn, Germany

Summary of the talk • Molecular Epidemiology of HIV Subtypes in India. • Drug resistant genotyping • EuResist study: INDIA (Preliminary Observations)

First Case of HIV/AIDS First Case of HIV/AIDS identified among the commercial sex worker in Tamilnadu, southern Part of India. NACO Annual Report, 2009-10

Trends in HIV Incidence NACO Annual Report, 2009-10

Mode of Transmission NACO Annual Report, 2009-10

HIV-1 Molecular Epidemiology in India

HIV-1 Molecular Epidemiology Subtype C

Prevalence of HIV-1 Subtypes in India* 94% * Based on Data available in Los Alamos Database

Trends in HIV-1 Molecular Epidemiology in India N=1374 Neogi et al, unpublished

Neogi et al 2009 , IJEB

Study Sites ● PGIMER, Punjab ● NII, New Delhi ● ● RDG Medical RIMS, College, Ujjain Manipur KR Hospital, Mysore ● ● SJMC, Bangalore

Current Cohort: N=143 * Data based on two gene sequences/patients Till Jan, 2011

Region wise distribution of HIV-1 subtypes

Drug Resistance Genotyping First I want you to get genotype test done to check resistance

Drug Resistance Genotyping: Transmitted Drug Resistance  Major DRM: None  Accessory/minor DRM: 9.56% (E138A, L210LS)  Polymorphisms Neogi et al 2010, AIDS Res Hum Retroviruses

Acquired Drug Resistance Drug Resistance Profile: ART Experienced Patient with VL >1000 copies/ml (n=92) NRTI NNRTI Neogi et al; unpublished

Selection of NNRTI Mutations: (n=92)

Cross-resistance to Etravirine

INDIA (Preliminary Observations)

EuResist Prediction: ART Naïve Group: 50 Adults ready to initiate ART. ART Experienced Group: 70 Adults on ART and viral load >1000 copies/ml. Patient Demography, Clinical and genetic parameter fed into EuResist Engine: 1.Sequence/Mutation Profile 2.Drugs to be used to build the treatment regimen 3.Patient past reg imen 4. Viral load, CD4 count, Age, Sex, mode of transmission.

First Line Regimen NACO Regimen: AZT/D4T+3TC +NVP/EFV

Second Line Regimen N=70 NACO Regimen: TDF+AZT+3TC +LPV/r Neogi et al; unpublished

What are the other options?? Co-receptor Antagonist !!!!! Neogi et al 2010, AIDS Res Ther

Summary  Subtype C is predominant but recombinant forms are in increasing  The level of transmitted drug resistance in India is <5%.  Evolution of RT region is sluggish. Cross-resistance to ETR and the pattern of NNRTI-mutations in  nevirapine-exposed patients suggests that use of nevirapine as first- line NNRTI in resource constrained settings may be reconsidered.  CCR5 antagonist may work better in India as conserved co- receptor usage were identified in Indian C strains.

Acknowledgements Dr. Anita Shet, SJMC Dr. Ayesha De Costa, KI Lab Members: Mr. Soham Gupta, Ms. Pravat Nalini Sahoo, Ms. Shwetha D Rao, Mr. Raj Mahendran Prof. Anders Sonnerborg, KI Dr. Maria L Ekstrand, UCSF (PI- Prerana Study) HIVIND and Prerana Study Team National AIDS Control Organization Indian Council of Medical Research, NIH and EU FP7 Our patients