INH Prophylaxis Therapy (IPT) should NOT be

implemented for all HIV patients in the Asia Pacific

Thuy Le, MD DPhilDuke University School of Medicine, USAOxford University Clinical Research Unit

Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

No conflicts of interest

➢ TB is the number one killer of HIV patients, accounting for more than 25% of HIV-associated deaths. The risk of reactivated and new TB infection is 20-37 times higher in HIV than in non-HIV-infected individuals

➢ The strategies to prevent TB in HIV include early ART and the three Is: Intensive Case Finding, IPT, and Infection Control. IPT has been recommended by the WHO for all HIV-infected individuals including pregnant women and children, regardless of CD4 count, ART status, and previous TB treatment since 2011. Strong Recommendation, High Quality of Evidence.

➢ Global IPT uptake and implementation remain very slow (1/30 millions PLHIV in 2016)

IPT does NOT have the same benefit/harm ratios for all HIV

patients in the Asia Pacific

Stable, high CD4 count, virologicallysuppressed, TST/IGRA (-)

Starting ART, high CD4 count, TST/IRGA (-)

Starting ART, low CD4 count,

Cases

➢ 45 year old man, ex IDU, on first-line ART for 8 years who

has been well and stable, viral load undetectable for 5 years

under my care. He has no prior history of TB. CD4 count

of 600.

➢ 38 year old woman with a history of TB meningitis,

history treatment failure on 2nd line ART with LPV/r for

over 3 years, stable, viral load undetectable, CD4 count 400.

➢ 23 year old man who completed a 6 month course of

pulmonary TB 6 months ago, viral load undetectable, CD4

is 200.

Distribution of HIV patients along the TB risk spectrum

Virologicallysuppressed on long-term ART TST/IRGA (-)

Asymptomatic starting ART, TST/IRGA (-)

Asymptomatic starting ART, TST/IRGA (+)

Symptomatic Starting ART

50%

Important barriers to implementation in the Asia

Pacific region

➢ Concerns of INH hepatotoxicity, given the high burden of

viral hepatitis coinfection and alcoholic hepatitis in the

region, pill burden, adherence, and INH resistance

development

➢ Uncertainty of efficacy in the setting of very high INH

resistance (up to 25%) compared to Africa (<5%)

➢ Lack of evidence of benefits in patients who are

virologically suppressed on long-term ART with high CD4

counts and those who are TST negative

64% of TB cases in 2015 occur in the Asia Pacific region

TB incidence

From: Treatment of latent tuberculosis infection in HIV infected persons Akolo C, Adetifa I, Shepperd S, Volmink J.. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD000171.

Cochrane of 12 placebo controlled RCT in IPT

TST (+)

TST unknown

TST (-)

All caused mortality

•Use of Isoniazid Preventive Therapy for Tuberculosis Prophylaxis Among People Living With

HIV/AIDS: A Review of the Literature

•Briggs, Melissa A. et al. JAIDS 2015

Systematic review of 41 studies on ITP

Reduction of TB incidence is observed in TST (+)

but not in TST (-) individuals

TST (+)

TST (-)

No evidence for a mortality benefit in TST (+) or (-)

individuals

TEMPRANO trial and post-trial follow up design

Temprano trial results

Morbidity benefit is driven primarily by Early ART

NEJM 2015

Temprano long-term follow up results

Lancet Global Health 2017

IPT: 16 deathsNo IPT: 23 deaths

Temprano: mortality by IGRA test

There was a clear mortality benefit during the first 30 month (duration of main trial) in IGRA (+) but not in IGRA (-) patients

IGRA (+)

IGRA (-)

JAIDS. April 2016

Meta-analysis of 13 studies• N=18,095 in INH group, N=17,985 in control

group• Only 158 isolates in the INH group and 328

isolates in the control group were available• RR for resistance was 1.45 (95% CI: 0.85–

2.47)• Studies from USA, Africa (Kenya, Uganda,

Zambia), and Europe (Spain)

Emerg Infec Dis. CDC. May 2006

• There are no clear benefits of IPT in TST negative HIV patients, particularly those who are virologically suppressed on long-term ART

• Intensive Case Finding (ICF) should include ICF of latent TB infections, just as recommended for non-HIV infected individuals

• RCTs should be done in countries with high TB/HIV prevalence in the Asia Pacific to inform policy in the region

• TST is feasible in rural and urban settings and should be implemented now in a diagnostic-driven approach to IPT to reduce TB incidence and to improve treatment acceptability, reducing unneccessary treatment, toxicity, and costs

IPT should NOT be implemented for all HIV

patients in the Asia Pacific

• Diagnostic driven approach to IPT, with yearly testing for

latent TB in HIV patients who are stable on ART

• Placebo controlled RCTs conducted in the Asia Pacific

region:

➢ comparing a diagnostic driven approach vs. the WHO

mass treatment approach evaluating long morbidity,

mortality, tolerability, drug resistance, and cost

effectiveness

➢Comparing different TB regimens, combination/short

course therapy vs. INH

I advocate for