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 ( 2010)

  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 patiens centers ~ 400 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=450,000approxi) till April 2011

• Govt. programs (200 ART centres): `
• Govt. programs (200 ART centres): `

404,882 404,882 Private hospitals and NGOs: Private hospitals and NGOs: ~ 30,000 ~ 30,000-

• 50,000

50,000

Treatment policy

NACO ART Guidelines NACO ART Guidelines

1st line HAART

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

Switching to Second-Line Treatment

WHO Guidelines 2006

YRGCARE

>16,000 patients registered for care >16,000 patients registered for care

• >7000 patients on HAART

>7000 patients on HAART VCT VCT

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

AIDS Clinical Trials Group (ACTG)/NIH AIDS Clinical Trials Group (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 Univ

California, Rush Univ-

• Chicago, Harvard

Chicago, Harvard Univ Univ-

• MA, Emory Univ

MA, Emory Univ-

• Atlanta, Stanford Univ

Atlanta, Stanford Univ-

• California,Treat Asia

California,Treat Asia-

• NCHECR, Karolinska Inst

NCHECR, Karolinska 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.

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

CD4 Count

Viral Load

Virologic failure

Immunologic failure

Clinical failure

Drug Resistance

Severe mutations following WHO immunologic failure- Chennai HIV cohort study

Total no.of patients registered for care: 10127 Total no.of patients registered for care: 10127 No.pts initiated on 1 No.pts 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 pts switched to 2 No.of 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 et al CID 2009; CROI 2008 Kumarasamy 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.

Sequencing Therapy in 2011 and Beyond: How Many Tries Do You Get?

2 NRTIs + 2 NRTIs + 1 NNRTI 1 NNRTI 3 NRTIs + 3 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 inhibitor(s) + ?
• ther entry inhibitor(s) + ?

Sequencing Therapy in 2011 and Beyond: How Many Tries Do You Get?

2 NRTIs + 2 NRTIs + 1 NNRTI 1 NNRTI 3 NRTIs 3 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 inhibitor(s) + ?
• ther entry inhibitor(s) + ?

Sequencing Therapy in 2011 and Beyond: How Many Tries Do You Get?

2 NRTIs + 2 NRTIs + 1 NNRTI 1 NNRTI 3 NRTIs/ 3 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 inhibitor(s) + ?
• ther entry inhibitor(s) + ?

2nd line Trials

Secondline International Trial Secondline International Trial-

• NCHER

NCHER Multicenter Study of Options for Multicenter Study of Options for SE SEcond cond-

• L

Line ine E Effective ffective C Combination

• mbination T

Therapy (SELECT) herapy (SELECT)-

• ACTG 5273

ACTG 5273

Phase IIIb/IV, international, randomised, open label study compa Phase IIIb/IV, international, randomised, open label study comparing ring two regimens .The study will run for 96 two regimens .The study will run for 96-

• weeks

weeks ritonavir boosted lopinavir (LPV/r) + 2N(t)RTIs ritonavir boosted lopinavir (LPV/r) + 2N(t)RTIs vs vs

• II. ritonavir boosted lopinavir (LPV/r) +
• II. ritonavir boosted lopinavir (LPV/r) + raltegravir

raltegravir

Saravanan et al., CROI 2010

Summary of PI and RT Drug Resistance

Saravanan et al., CROI 2010

Saravanan et al., CROI 2010

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).

TREAT Asia (TASER-S&M) TREAT Asia (TASER-S&M)

1 2 3 8 7 6 9 11 10 5 4 12 13 Current participating sites: 1 Beijing Ditan Hospital, Beijing 2 Queen Elizabeth Hospital, Hong Kong, 3 Taipei Veterans General Hospital and AIDS Prevention and Research Centre, Taipei 4 HIV Project, Ruby Hall Clinic, Pune 5 YRG Centre for AIDS Research and Education, Chennai 6 HIV-NAT/The Thai Red Cross AIDS Research Centre, Bangkok 7 Ramathibodi Hospital, Bangkok 8 Research Institute for Tropical Medicine, Manila 9 Hospital Kuala Lumpur, Kuala Lumpur 10 University of Malaya, Kuala Lumpur, 11 Tan Tock Seng Hospital, Singapore 12 Udayana Medical School, Bali Potential participating sites: 13 Hospital for Tropical Medicine, Ho Chi Minh City

Barriers and facilitators to antiretroviral medication adherence among patients with HIV in Chennai, India: A qualitative study (Kumarasamy N et al., AIDS Patient care& STDs. 2005) Cost Cost Disclosure Disclosure-

• Stigma

Stigma Family members Family members-

• DOT

DOT Karolinska Karolinska Institute, Sweden/ European Union Institute, Sweden/ European Union

Text messages (SMS) and Telephone reminders Text messages (SMS) and Telephone reminders

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