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Professor of Medicine and Epidemiology
University of North Carolina School of Medicine
Director, AIDS Clinical Trials Unit
University of North Carolina
Chapel Hill, North Carolina
Joseph J. Eron, Jr., MD: consultant/advisor/speaker: Gilead Sciences, GlaxoSmithKline, Merck, ViiV Healthcare; researcher: Gilead Sciences, Janssen, ViiV Healthcare.
The high efficacy of recommended 3-drug tenofovir-containing antiretroviral therapy (ART) regimens against both HIV and hepatitis B virus (HBV) has lessened concern regarding the HBV immune status of people receiving HIV treatment. This tendency is understandable when considering that 3-drug ART inclusive of tenofovir disoproxil fumarate or tenofovir alafenamide (most often in combination with emtricitabine or lamivudine) essentially serves as an effective HBV pre-exposure prophylaxis regimen.
However, as the use of 2-drug ART regimens for HIV treatment continues to increase, including the long-acting injectable switch regimen of cabotegravir plus rilpivirine, so does the importance of ensuring that our patients have adequate HBV immunity.
Underscoring this concern is a recent case report of someone who indeed acquired acute HBV infection after switching to a 2-drug ART regimen. In this case report, the individual had been vaccinated against HBV infection, but retrospective serum testing demonstrated no detectable antibodies to hepatitis B surface antigen (HBsAg) 5 months after the second vaccination. This report also highlights the fact that people with HIV often have lower rates of protective immunity following standard HBV vaccination schedules compared with people without HIV.
In this context, I found an IDWeek 2022 presentation to be particularly compelling. It reported preliminary results of the phase III ACTG A5379 trial comparing the single-antigen adjuvanted HBV vaccine HepB-CpG (HEPLISAV-B) with a single-antigen nonadjuvanted (but aluminum adsorbed) HepB vaccine (Engerix-B) specifically in people with HIV.
The HepB-CpG vaccine was approved by the FDA in 2017 as a 2-dose HBV vaccine series for adults based on clinical trial results demonstrating, in a general adult population, a 95.2% seroprotection rate (SPR) (defined as antibody to HBsAg [HBsAb] ≥10 mIU/mL) after 2 doses of HepB-CpG administered over 4 weeks vs an 80.7% SPR after 3 doses of a comparator HBV vaccine administered over 24 weeks. The key distinctive feature of HepB-CpG is that it contains a novel adjuvant that binds to TLR9, stimulating the immune response to HBsAg. Data on HepB-CpG vaccination in people with HIV are limited, prompting the ACTG A5379 trial.
The ACTG A5379 trial is a prospective, open-label phase III study evaluating 2 groups of people with HIV: nonresponders to previous HBV vaccination who are randomized to receive a 2- or 3-dose series of HepB-CpG or a 3-dose series of HepB (group A) and participants without previous HBV vaccination who receive a 3-dose series (Weeks 0, 4, and 24) of HepB-CpG (group B). Participants are required to have been receiving ART for >56 days before study entry and have a CD4+ cell count >100 cells/mm3 and HIV-1 RNA <1000 copies/mL. The study defined SPR as HBsAb ≥10 mIU/mL at Week 28 or 4 weeks after the third dose if the third dose was received later than Week 24.
At IDWeek 2022, Sherman and colleagues reported results from participants enrolled in group B. The SPR was 100% (95% CI: 94.7%-100%) among 68 participants included in the primary analysis approach (which excluded 6 individuals who did not have results within the visit window). In a sensitivity analysis that included all 74 participants in group B (missing SPR data imputed using results before and after the missed visit), the SPR also was 100% (95% CI: 95.1%-100%), pending quality control assessment of the missing data. Responses included 88.2% who achieved HBsAb >1000 mIU/mL.
Although this was a single-arm analysis among participants with relatively high CD4+ cell counts (median: 625 cells/mm3; interquartile range: 473-829), these preliminary findings are encouraging regarding the ability of this vaccine to elicit strong seroprotective responses in people with HIV. It will be interesting to see forthcoming results from the randomized evaluation among individuals with previous nonresponse to HBV vaccination.
In my own practice, I plan to pay closer attention to the hepatitis B antibody status of everyone with HIV in my care, because even if they are not currently contemplating a switch to 2-drug ART, they may decide to consider that option in the future, particularly with the potential for even longer-acting regimens on the horizon. For me, this will include determining if patients are HBsAb positive, not just HBsAg negative, and clearly documenting this in the medical record.
What are your thoughts on how these data affect clinical practice? Would you consider routinely testing people with HIV in your care for immunity to HBV rather than only HBsAg negativity before initiating or switching to a 2-drug ART regimen? Join the discussion by posting a comment.