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![Page 1: 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.](https://reader031.fdocuments.net/reader031/viewer/2022032801/56649ddb5503460f94ad1f90/html5/thumbnails/1.jpg)
The safety of HIV pre-exposure prophylaxisin 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 byNIH/NIAID/DAIDS
and drug donated byGilead Sciences
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Marc Solomon, MDIAS/ANRS Lange-Van Tongeren Prize 2015
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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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Lima
IquitosGuayaquil
Sao Paulo
Rio de Janeiro
Boston
San Francisco
Cape Town
Chiang Mai
Solomon IAS Vancouver 2015
Sites 11Total Screened 4459
Total Enrolled 2499
iPrEx RCT Study Sites
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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
Solomon IAS Vancouver 2015
(isolated anti-HBc+; all were DNA-)
(anti-HBc IgM+)
13 with chronic hepatitis B infection were enrolled:6 were randomized to FTC/TDF, 7 were randomized to placebo.
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No hepatitis flare with PrEP gaps
Solomon IAS Vancouver 2015 HBeAg-; anti-HBe+
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No hepatitis flare with PrEP gaps
Solomon IAS Vancouver 2015 HBeAg-; anti-HBe+
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No hepatitis flare with PrEP gaps
Solomon IAS Vancouver 2015 HBeAg-; anti-HBe+
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No hepatitis flare with PrEP gaps
Solomon IAS Vancouver 2015 HBeAg-; anti-HBe+
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No hepatitis flare after stopping PrEP
Solomon IAS Vancouver 2015 HBeAg-; anti-HBe+
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No hepatitis flare after stopping PrEP
Solomon IAS Vancouver 2015 HBeAg+; anti-HBe-
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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
• 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+, DNA-
Solomon IAS Vancouver 2015
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Vaccine Acceptance and Response
Solomon IAS Vancouver 2015
• 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 BVaccineDoses Received
% 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.
Solomon IAS Vancouver 2015
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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.
Solomon IAS Vancouver 2015
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This work was made possibleby the participants
and their communitieswho believed that research
could improve their lives