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

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

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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.

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Screening HBV serostatus

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(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-

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Vaccine Acceptance and Response

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• 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.

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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

This work was made possibleby the participants

and their communitieswho believed that research

could improve their lives