Bulevirtide works well against chronic hepatitis D, HIV/HBV/HDV coinfection

Patients with hepatitis delta virus (HDV) show increased virologic and biochemical responses with longer bulevirtide (BLV) treatment for over 96 weeks, with no new safety concerns, as shown in a study presented at CROI 2024.

Additionally, two HDV patients with HIV and hepatitis B virus (HBV) coinfection have achieved a combined response, with good BLV tolerability. However, more research is warranted with BLV therapy in those with HIV/HBV/HDV, according to the investigators, led by Dr Heiner Wedemeyer from Medizinische Hochschule Hannover in Hannover, Germany.

Combined response was defined as undetectable HDV RNA or ≥2 log₁₀ IU/mL decline from baseline to alanine aminotransferase (ALT) normalization.

“BLV is a first-in-class, entry inhibitor, approved in the EU for the treatment of chronic hepatitis D (CHD),” the investigators said. “Limited data exists on the safety and efficacy of BLV in HIV/HBV/HDV coinfection.”

Wedemeyer and his team performed a week 96 analysis from the phase III MYR301 study to assess the safety and efficacy of BLV for over 96 weeks including in patients with HIV/HBV/HDV.

The study randomly assigned 150 patients with CHD into three groups: arm A (no active anti-HDV treatment for 48 weeks, followed by BLV 10 mg/d for 96 weeks; n=51) and arms B or C (immediate treatment with BLV at 2 mg/d [n=49] or 10 mg/d [n=50], respectively, each for 144 weeks, with follow-up of 96 weeks after end of treatment).

Investigators measured efficacy by combined, virologic, and biochemical response rates.

Baseline characteristics were similar across the three treatment arms (mean age 41.8 years, 57 percent males, 83 percent White, 47 percent compensated cirrhosis, mean HDV RNA 5.05 log10 IU/mL, ALT 110.9 U/L, and 61 percent on concomitant nucleos[t]ide analogue). [CROI 2024, abstract 735]

The study also enrolled two patients with HIV/HBV/HDV. At baseline, patient 1 (assigned to arm B) was 39 years of age, HCV ab neg, had undetectable HIV viral load (VL), CD4 786/mm³, and was being treated with tenofovir/lamivudine/etravirine. Patient 2 (arm C) was 40 years of age, HCV ab pos (HCV RNA neg), had undetectable HIV VL, CD4 559/mm³, and was on emtricitabine/tenofovir alafenamide/raltegravir.

Overall, patients in arms B and C showed comparable combined (55 percent and 56 percent, respectively), virologic (76 percent and 82 percent), and biochemical (63 percent and 64 percent) responses at week 96.

For patient 1, the key parameters from baseline to week 96 were as follows: HDV RNA 3,345,358 IU/mL to <50, HBV DNA 22 IU/mL to neg, HBsAg 18,000 to 6,400 IU/mL, and ALT 289 to 18 U/L. For patient 2, the key parameters were HDV RNA 425,354 IU/mL to <50, HBV DNA 17 IU/mL to <10, HBsAg 8,100 to 5,200 IU/mL, and ALT 97 to 26 U/L.

“At week 96, both HIV/HBV/HDV coinfected patients achieved combined virologic and biochemical response, and neither required changes to their antiretroviral therapy,” the investigators said.

In addition, BLV demonstrated safety and good tolerability. Both HIV/HBV/HDV patients did not discontinue treatment and had no serious adverse events or deaths attributed to BLV.