HIV treatment & ARV resistance issues in India Dr. N. - - PowerPoint PPT Presentation

HIV treatment & ARV resistance issues in India

• Dr. N. Kumarasamy
• Dr. N. Kumarasamy

Chief Medical Officer Chief Medical Officer

YRG Centre for AIDS Research and Education YRG Centre for AIDS Research and Education

VHS, Chennai, India VHS, Chennai, India Principal Investigator Principal Investigator-

• Chennai ACTG International

Chennai ACTG International Clinical Trials Unit/NIH Clinical Trials Unit/NIH

HIV Scenario in India ( 2009)

  2 to 3 million infections 2 to 3 million infections   Heterosexual transmission Heterosexual transmission   ` ` 0.35% 0.35% of adult population

• f adult population (1.2billion population)

(1.2billion population)   Growing number of AIDS cases Growing number of AIDS cases   HIV HIV-

• 1; Subtype C

1; Subtype C

Source : NACO Source : NACO

Natural history of HIV disease in South India (Kumarasamy et al.CID Jan 2003)

Opportunistic Infections

C r y p t

• c
• c

c a l m e n i n g i G a s t e r

• e

n t e r

• p

a t h y P C P C M V R e t i n i t i s R e c . B a c t . R e s p i r a t

• P

a p u l a r p r u r i t i c e r u E x t r a p u l m

• n

a r y T B P u l m

• n

a r y T u b e r c u l

• s

O r a l C a n d i d i a s i s M

• l

l u s c u m C

• n

t a g i

• s

u T

• x
• p

l a s m

• s

i s O H L C r y p t

• s

p

• r

i d i a l d i a r D e r m a t

• p

h y t e I n f e c t i H e r p e s Z

• s

t e r H e r p e s S i m p l e x

Mean CD4

325 300 275 250 225 200 175 150 125 100

Antiretroviral Drugs in India

1996……………..

nRTIs NNRTIs Nucleotide RTIs Protease inhibitors Fusion inhibitors Zidovudine(AZT) Lamivudine(3TC) Didanosine(ddI) Stavudine(d4T) Abacavir(ABC)

Emitricitabine(FTC)

Zalcitabine(ddC) Nevirapine Efavirenz Delaviridine Tenofovir Ritonavir Indinavir Saquinavir Nelfinavir Amprenavir Atazanavir Lopinavir/ Ritonavir Enfuvirtide (T20)

Kumarasamy et al.. Clinical Infectious Diseases 2005 Figure 2 : Incidence of opportunistic infection in patients with and without HAART, 1996-2003

2 4 6 8 10 12 1996 1997 1998 1999 2000 2001 2002 2003 Year

Cases per 100 person years

Incidence of any OI in people without HAART Incidence of any OI in people with HAART Incidence of TB in people without HAART Incidence of TB in people with HAART

Reduction in death rate following HAART

Kumarasamy, et al. Clin Infect Dis 2005

5 10 15 20 25 30 1997 1998 1999 2000 2001 2002 2003 Year Deaths per 100 Patient Years Observed 10 20 30 40 50 60 Percent of Patients with CD4 < 200 on HAART

GOI supported Access to ART

• NACO

NACO -

• 25 Centers

25 Centers-

• April 2004

April 2004

• Central Government Health Scheme (CGHS),

Central Government Health Scheme (CGHS),

• Employees State Insurance Corporation (ESIC), 9

Employees State Insurance Corporation (ESIC), 9 centers ~ 400 centers ~ 400 patiens patiens

• Armed Forces Medical Services, 3 centers, ~700

Armed Forces Medical Services, 3 centers, ~700 patients patients

• Hospitals administered by the Railways

Hospitals administered by the Railways 16 Centers, 16 Centers, ~500 patients ~500 patients

Access to ART in India (n=250,000approxi) till May 2009

• Govt. programs (200 ART
• Govt. programs (200 ART centres

centres): ` ): ` 220,000 220,000 Private hospitals and NGOs: ~ 30,000 Private hospitals and NGOs: ~ 30,000

Treatment policy

NACO ART Guidelines NACO ART Guidelines

1st line HAART

AZT/ AZT/d4T d4T + 3TC + NVP/EFV + 3TC + NVP/EFV TDF + FTC + EFV TDF + FTC + EFV

Switching to Second-Line Treatment

WHO Guidelines 2006

Treatment Failure and Drug Resistance: Virologic, Immunologic, and Clinical Definitions

CD4 Count

Viral Load

Virologic failure

Immunologic failure

Clinical failure

Drug Resistance

YRGCARE

>15,000 patients registered for care >15,000 patients registered for care

• >7000 patients on HAART

>7000 patients on HAART VCT VCT

( (OPD,Acute OPD,Acute care inpatient care inpatient facility,adherence facility,adherence/couple/family /couple/family counseling,Nutritional counseling,Nutritional Counseling, Pharmacy) Counseling, Pharmacy)

AIDS Clinical Trials Group (ICTU AIDS Clinical Trials Group (ICTU-

• ACTG)/NIH

ACTG)/NIH HIV Prevention Trial Network (HPTN)/NIH HIV Prevention Trial Network (HPTN)/NIH Brown University Brown University-

• RI, UCSD

RI, UCSD-

• California, Johns Hopkins

California, Johns Hopkins Univ Univ-

• MD, UCSF

MD, UCSF-

• California, Rush

California, Rush Univ Univ-

• Chicago, Harvard

Chicago, Harvard Univ Univ-

• MA, Emory

MA, Emory Univ Univ-

• Atlanta, Stanford

Atlanta, Stanford Univ Univ-

• California,Treat

California,Treat Asia Asia-

• NCHECR,

NCHECR, Karolinska Karolinska Inst Inst-

• Sweden.

Sweden.

www.yrgcare.org www.yrgcare.org

Virology & Molecular Biology Lab

Regional HIV Genotyping Lab for NIH

• 30 subtype C, 18 subtype B and 2 subtype D
• Clinical (ART treated and failing patients) n = 29
• Proficiency testing (PT) panels n=21

VQA, Rush University, USA n = 10 Teragenix, Abbott, USA n = 6 TAQAS, NRL, Australia n = 5

ViroSeqTM v2.0 vs. In-house

In-house assay performed well, which costs about 50% ($ 100) of the ViroSeqTM ($230), demonstrated a similar capacity to identify clinically relevant mutations compared to the ViroSeqTM.

Severe mutations following WHO immunologic failure- Chennai HIV cohort study

Total Total no.of no.of patients registered for care: 10127 patients registered for care: 10127 No.pts No.pts initiated on 1 initiated on 1st

st line HAART: 3739

line HAART: 3739

(AZT/d4T+3TC+NVP/EFV) (AZT/d4T+3TC+NVP/EFV)

Median CD4 at HAART initiation: 69 IQ (40 Median CD4 at HAART initiation: 69 IQ (40-

• 125)

125) No.of No.of pts switched to 2 pts switched to 2nd

nd line:

line: 336 (9%) 336 (9%) Median CD4 at switch : 144 (90 Median CD4 at switch : 144 (90-

• 199)

199) Median duration on 1 Median duration on 1st

st line 3.7yrs ( 2.2

line 3.7yrs ( 2.2-

• 6.3)

6.3)

Kumarasamy Kumarasamy et al CID 2009; CROI 2008 et al CID 2009; CROI 2008

79% of them had M184V, 79% of them had M184V, 71 % had NNRTI mutations, (K103N,Y181C,G190A) 71 % had NNRTI mutations, (K103N,Y181C,G190A) 60% had TAMS, (M41L,T215Y/F,K70R,L210W,K219E/Q) 60% had TAMS, (M41L,T215Y/F,K70R,L210W,K219E/Q) 11% had Q151M 11% had Q151M 5% had K65R and 5% had K65R and 5% had L74V. 5% had L74V. 26% had 3 or more NNRTI mutations 26% had 3 or more NNRTI mutations This data clearly warns that patients with immunological failure This data clearly warns that patients with immunological failure with standard with standard WHO criteria have severe mutations and WHO criteria have severe mutations and which can jeopardize future 2nd which can jeopardize future 2nd line NRTI options and newer drugs. line NRTI options and newer drugs.

ABC or 3TC (±AZT) ddI or TDF EFV or NVP

Second line ARV drugs in adults and adolescents

PI/r

Sequencing Therapy in 2009 and Beyond: How Many Tries Do You Get?

2 2 NRTIs NRTIs + + 1 NNRTI 1 NNRTI 3 3 NRTIs NRTIs + + 1 PI/RTV 1 PI/RTV 1 PI/RTV + 1 PI/RTV + Integrase Integrase/CCR5 inhibitor /CCR5 inhibitor ± ± NRTIs NRTIs 2 2nd

nd Gen NNRTI + ENF + other CCR5 inhibitor

Gen NNRTI + ENF + other CCR5 inhibitor ± ± PI/RTV PI/RTV Maturation inhibitor + Maturation inhibitor +

• ther entry
• ther entry inhibitor(s

inhibitor(s) + ? ) + ?

Sequencing Therapy in 2009 and Beyond: How Many Tries Do You Get?

2 2 NRTIs NRTIs + + 1 NNRTI 1 NNRTI 3 3 NRTIs NRTIs + + 1 PI/RTV 1 PI/RTV 1 PI/RTV + 1 PI/RTV + Integrase Integrase/CCR5 inhibitor /CCR5 inhibitor ± ± NRTIs NRTIs 2 2nd

nd Gen NNRTI + ENF + other CCR5 inhibitor

Gen NNRTI + ENF + other CCR5 inhibitor ± ± PI/RTV PI/RTV Maturation inhibitor + Maturation inhibitor +

• ther entry
• ther entry inhibitor(s

inhibitor(s) + ? ) + ?

Sequencing Therapy in 2009 and Beyond: How Many Tries Do You Get?

2 2 NRTIs NRTIs + + 1 NNRTI 1 NNRTI 3 3 NRTIs/ NRTIs/Integrase Integrase + + 1 PI/RTV 1 PI/RTV 1 PI/RTV + 2 1 PI/RTV + 2nd

nd Gen NNRTI/CCR5 inhibitor

Gen NNRTI/CCR5 inhibitor ± ± NRTIs NRTIs ENF + other CCR5 inhibitor ENF + other CCR5 inhibitor ± ± PI/RTV PI/RTV Maturation inhibitor + Maturation inhibitor +

• ther entry
• ther entry inhibitor(s

inhibitor(s) + ? ) + ?

Saravanan et al., 17th CROI 2010, San Francisco, USA

PR and RT Mutations

Genotyping in Naïve population-Indian studies

Primary drug resistance has been reported ranging from Primary drug resistance has been reported ranging from 2.5% 2.5% to 17.5% to 17.5% ( (Hira Hira et al.,2 et al.,2004, 004, Deshpande Deshpande et al et al.,2005 ; .,2005 ; Balakrishnan Balakrishnan et al., et al., 2005 ; 2005 ; Arora Arora et al., 2008 ; et al., 2008 ; Lal Lal et al., 2008 et al., 2008 ). ). Few studies reported no major resistance Few studies reported no major resistance ( (Eshleman Eshleman et al., et al., 2005 ; 2005 ; Kandathil Kandathil et al., et al., 2008). 2008).

The antiretroviral roll out for HIV in India – strengthening capacity to promote adherence and patient follow-up-HIVIND

Support: European Union, FP 7 Support: European Union, FP 7 – – 2009 2009

Partners:

• 1. Divn of International Health, Karolinska Institutet, Stockholm,

Sweden

• 2. St. John’s National Academy of Health Sciences, Bangalore,

India

• 3. YRGCARE, VHS, Chennai, India
• 4. Dept of International Health, Tampere Univ Medical School,

Finland

• 5. Hanoi Medical University
• 6. Cavidi AB, Uppsala, Sweden