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