Impact of Antiretroviral Therapy on TB disease in Resource Limited Settings

Dr. N. KumarasamyDr. N. Kumarasamy

Chief Medical OfficerChief Medical Officer

YRGCARE Medical CentreYRGCARE Medical Centre

Chief-Chennai Antiviral Research and Treatment (CART) Clinical Research Site/NIHChief-Chennai Antiviral Research and Treatment (CART) Clinical Research Site/NIH

Voluntary Health ServicesVoluntary Health Services

Chennai, India Chennai, India

40

35

1110

84 3 2 1 1

0

5

10

15

20

25

30

35

40P

erc

enta

ges

Opportunistic Infections

Oral Candidiasis Pulmonary tuberculosis

Herpes Simplex Extra Pulmonary Tuberculosis

Herpes Zoster PCP

Toxoplasmosis Cryptococcal Meningitis

Cryptosporidial Diarrhoea CMV Retinitis

Spectrum of OI (n= 6815) –YRGCARE cohort: Jun1996- Aug 2004

Kumarasamy et al. IJMR 2005.

Co-factors relating to progression of patients with HIV disease

Kumarasamy et al., CID Jan 2003

Co-factors OR 95% CI P-value HIV associated illness

Pulmonary TB

PCP

Cryptococcal

Toxoplasmosis

Co-infection

HCV

3.52

4.47

6.98

2.57

7.84

1.96-6.32

2.67-7.51

4.1-11.97

1.27-5.2

1.61-38.22

<0.001

<0.001

<0.001

0.01

0.01

HPTN 052• 1,750 heterosexual serodiscordant couples in 1,750 heterosexual serodiscordant couples in

resource-constrained countries randomized to receive resource-constrained countries randomized to receive ART early (CD4 350-550 cells/µL) or defer until CD4 < ART early (CD4 350-550 cells/µL) or defer until CD4 < 250 cells/µL250 cells/µL

Event Rates Early ART Deferred ART HR P-value

Transmission Rate per 100 pt-years

(95% CI)

0.3 (0.1-0.6)

2.2 (1.6-3.1)

0.11(0.04-0.32)

< 0.001

Clinical Event Rate per 100 pt-years

(95% CI)

2.4(1.7-3.3)

4.0(3.5-5.0)

0.59(0.40-0.88)

<0.001

Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC,Kumarasamy N et al, NEJM, 2011Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC,Kumarasamy N et al, NEJM, 2011

• In South Africa, early ART was cost-saving over a 5-year period.In South Africa, early ART was cost-saving over a 5-year period.• In both South Africa and India, early ART was projected to be In both South Africa and India, early ART was projected to be

very cost-effective over a lifetime. very cost-effective over a lifetime. • With individual, public health, and economic benefits, there is a With individual, public health, and economic benefits, there is a

compelling case for early ART for serodiscordant couples in compelling case for early ART for serodiscordant couples in resource-limited settings. resource-limited settings.

Summary of Changes in Recommendations in WHO 2013 ART Guidelines-When to Start in Adults

AIDS-related deaths to be averted due to the new treatment guidelines

11

Low-income Lower middle-income

High-incomeUpper middle-income

Year of starting ART

Mea

n C

D c

ount

(ce

lls/µ

L)

Estimates from random-effects model adjusted for age, sex and year of starting ART, 2002-2009

Mean CD4 count at ART initiation is below 200 in LMIC

Source: Egger M. CROI 2012

2002 2009 2002 2009 2002 2009 2002 2009

IeDEA JAIDS 2014

Source: UNAIDS.

• Simulation model of HIV testing and treatmentSimulation model of HIV testing and treatment- Prevalence and Incidence in different groupsPrevalence and Incidence in different groups- Cost of testingCost of testing

Conclusion:Conclusion: Voluntary HIV screening among National Voluntary HIV screening among National population population every 5 yrs every 5 yrs offers substantial clinical benefit and offers substantial clinical benefit and cost effective. cost effective. Annual screening Annual screening is cost effective among is cost effective among high risk population and in high prevalent districtshigh risk population and in high prevalent districts

Sequencing Therapy in in Resource Limited Setting

2 NRTIs(TDF+3TC/FTC) + 2 NRTIs(TDF+3TC/FTC) + 1 NNRTI (EFV)1 NNRTI (EFV)

2 NRTIs(AZT+3TC) + 2 NRTIs(AZT+3TC) + 1 PI/RTV(ATVr or LPVr)1 PI/RTV(ATVr or LPVr)

1 PI/RTV(DRVr) + 1 PI/RTV(DRVr) + Integrase Integrase ± ± // CCR5 CCR5 inhibitor/ inhibitor/ 22ndnd Gen NNRTI (ETV) Gen NNRTI (ETV)

Conclusions

• Global progress on scale-up of ART has been extraordinary- Global progress on scale-up of ART has been extraordinary- 15 millions on ART. 15 millions on ART.

• Decrease in morbidity and mortalityDecrease in morbidity and mortality

• Declining incidence of HIVDeclining incidence of HIV

• Sustainability of ARVs-Sustainability of ARVs-This will require forward-looking This will require forward-looking policies, more effective and innovative approaches, together policies, more effective and innovative approaches, together with further investments with further investments

• Prevention of transmission of resistance strainsPrevention of transmission of resistance strains

• Prevention and management of NCDsPrevention and management of NCDs

• ARVs for treatment and prevention are a powerful tool ARVs for treatment and prevention are a powerful tool towards ending the HIV epidemictowards ending the HIV epidemic