Download Pre-Exposure Prophylaxis (PrEP) Initiative

The safety of HIV pre-exposure prophylaxis
in the presence of hepatitis B infection
Marc M. Solomon, Mauro Schechter, Albert Y. Liu,
Vanessa McMahan, Juan V. Guanira, Robert J. Hance,
Suwat Chariyalertsak, Kenneth Mayer, Robert M Grant,
for the iPrEx study team.
Sponsored by
NIH/NIAID/DAIDS
and drug donated by
Gilead Sciences
Marc Solomon, MD
IAS/ANRS Lange-Van Tongeren Prize 2015
Background
• Oral FTC/TDF, or TDF, prevent HIV acquisition,1-4 and are active against HBV.
• Withdrawal of anti-HBV medications, or the emergence of drug resistance,
may allow HBV rebound, which may cause acute on chronic hepatic injury (or
flare).5-6
▫ The risk of hepatitis flare is lower with lower pre-treatment clinical stage.7
▫ HBV resistance to TDF has not been documented.8
▫ There were no HBV flares after withdrawing TDF PrEP among 23 women
with HBsAg and normal AST and ALT at enrollment.9
▫ HBsAg+ persons were excluded from other PrEP trials.
• The iPrEx study1 included people with HBsAg+ at enrollment.
1. Grant NEJM 2010; 2. Baeten NEJM 2012; 3. Thigpen NEJM 2012; 4. Choopanya Lancet 2013;
5. Bessesen Clin Infect Dis 1999 28(5):1032-5; 6. Mondou Clin Infect Dis 2005 41(5):e45-7; 7. Thio Clin Infect Dis
2005 41(7):1035-40. 8. Matthews Clin Infect Dis 2013;56(9):e87–948. 9. Peterson PLoS Clin Trials 2007;2(5):e27.
Solomon IAS Vancouver 2015
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iPrEx RCT Study Sites
Sites
Total Screened
Total Enrolled
11
4459
2499
San Francisco
Boston
Chiang Mai
Iquitos
Guayaquil
Lima
Solomon IAS Vancouver 2015
Rio de
Janeiro
Sao Paulo
Cape Town
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Methods
• Inclusion / Exclusion for iPrEx.
▫ MSM and TGW reporting HIV risk factors.
▫ AST and ALT <2 x ULN.
▫ Total Bilirubin normal or near normal.
▫ Anti-HBc IgM negative.
• HBV serologies at screening: anti-HBs, anti-HBc, HBsAg.
• If HBsAg+ or isolated anti-HBc+.
▫ HBV DNA (after visits were completed).
▫ HBeAg and anti-HBe were tested.
• HBV susceptible people were offered HBV vaccine.
• HBsAg+ participants had extended followup.
▫ At 4, 8 and 12 weeks after stopping PrEP.
Solomon IAS Vancouver 2015
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Screening HBV serostatus
(anti-HBc IgM+)
(isolated anti-HBc+; all were DNA-)
13 with chronic hepatitis B infection were enrolled:
6 were randomized to FTC/TDF,
7 were randomized to placebo.
Solomon IAS Vancouver 2015
7
No hepatitis flare with PrEP gaps
Solomon IAS Vancouver 2015
HBeAg-; anti-HBe+
8
No hepatitis flare with PrEP gaps
Solomon IAS Vancouver 2015
HBeAg-; anti-HBe+
9
No hepatitis flare with PrEP gaps
Solomon IAS Vancouver 2015
HBeAg-; anti-HBe+
10
No hepatitis flare with PrEP gaps
Solomon IAS Vancouver 2015
HBeAg-; anti-HBe+
11
No hepatitis flare after stopping PrEP
Solomon IAS Vancouver 2015
HBeAg-; anti-HBe+
12
No hepatitis flare after stopping PrEP
Solomon IAS Vancouver 2015
HBeAg+; anti-HBe-
13
Acute HBV Infection on FTC/TDF PrEP
• 25 year old
▫ Starting FTC/TDF PrEP
 Normal LFTs
 Negative serologies
 HBV DNA 30,684
▫ 4 weeks of PrEP
 AST 205, ALT 669
 HBsAg-, anti-HBs-,
 anti-HBc IgM+
▫ 6 weeks of PrEP
 LFTs normal
▫ 28 weeks of PrEP
 Anti-HBs+, anti-HBc+
 HBV immunity
Solomon IAS Vancouver 2015
• 35 year old
▫ Screening
 Normal LFTs,
 sAg+, eAg+, anti-HBc IgM▫ Started PrEP (14d later)
 AST 214, ALT 304
▫ 8 days on FTC/TDF
 AST 1473, ALT 1061,
 sAg+, eAg+, anti-HBc IgM+
 Stopped FTC/TDF
▫ 12 weeks on study
 Normal AST/ALT
 Restarted FTC/TDF
▫ 28 and 72 weeks on FTC/TDF
 Normal AST/ALT
 sAg-, eAg-, eAb+, DNA14
Vaccine Acceptance and Response
• Vaccine Uptake
▫ 1633 were eligible for Hep. B immunization
▫ 1587 (97.2%) received at least one dose
▫ 1383 (84.7%) received all three doses
• Vaccine Response
Hep B
Vaccine
Doses
Received
Solomon IAS Vancouver 2015
% Immune
(anti-HBs+)
N immune /
N evaluated
3
86.9%
1021/1175
2
74.5%
38/51
1
44.4%
12/27
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Conclusions Regarding HBV and PrEP
• HBV vaccination rates are low, despite WHO recommendations.
▫ HBV vaccination uptake was high when offered free of charge.
• With isolated anti-HBc+ (anti-HBs-, HBsAg-).
▫ Was relatively common (5.5%).
▫ None had detectable HBV DNA.
▫ No hepatitis flare during and after FTC/TDF PrEP use.
• With HBsAg+ …
▫ Viral rebound but no clinical relapses during and after PrEP use.
▫ No TDF or FTC drug resistance during or after PrEP use.
• Acute HBV infection resolved to immunity in 2 starting FTC/TDF PrEP.
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Implications
• PrEP provides an opportunity to offer Hepatitis B vaccination.
• The HBsAg+ persons with normal or near normal AST and ALT
have a very low risk of hepatitis B flare when stopping HBV
active medications.
• HBsAg screening delays PrEP initiation and provides unclear
safety benefits.
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This work was made
by the
possible
participants
and their communities
who believed that research
could improve their lives