Raltegravir-Based ART Shows Lower Rates of Hepatoxicity

Replacing efavirenz (EFV) with raltegravir (RAL) in antiretroviral therapy (ART) may decrease hepatotoxicity in patients coinfected with HIV and hepatitis C virus (HCV), according to study results presented at the virtual 2020 Conference on Retroviruses and Opportunistic Infections, held March 8 to 11, 2020.

Drug-induced liver injury can result following the initiation of ART but is more common in patients who have HIV/HCV coinfection. However, previous clinical trials that have compared data on hepatotoxicity and the antiviral agents used have largely excluded this population. Therefore, this randomized controlled open-label trial tested their hypothesis to determine whether the rate of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) toxicity was higher in patients starting first-line combination ART with EFV-based vs RAL-based regimens.

In total, 80 patients aged ³18 years who were ART-naïve, HCV RNA-positive, HBSAg-negative, not receiving rifampin, had CD4 <500 at any disease stage (by World Health Organization criteria), an AST/ALT £80 U/L, a CrCl ³60 mL/min, and no decompensated cirrhosis were included from the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam from 2014 to 2017. Patients were randomly assigned (1:1) to receive either EFV-based ART (n=41) or RAL-based ART (n=38) for 72 weeks.

Particpants’ levels of AST, ALT, and bilirubin were obtained monthly and levels of CD4, HIV RNA, and lipids along with a fibroscan were obtained on weeks 0, 24, 48, and 72. The primary outcome was the rate of AST and ALT toxicity that were grade >2. The secondary outcome was HIV RNA <150 copies/mL and time to AIDS or death.

The results demonstrated that EFV-based ART had a higher association with hepatotoxicity compared with RAL-based ART. Compared with the RAL group, a high risk for hepatotoxicity was observed in the EFV group that occurred mostly during the first 12 weeks: ALT 62.2% vs 73.0% (P =.14) and AST: 42.5% vs 61.8% (P =.10), respectively. Virologic suppression was similar between the participants in both groups at week 72 with 85.7% and 87.9% achieving viral suppression in the EFV and RAL groups, respectively. Although it was not statistically significant, compared with the RAL group, EFV was associated with lower CD4 gain (224 vs 170 cells/µL) and lower reduction of fibroscan value (−0.70 vs −0.40 kPa).

Compared with the EFV group, the RAL group had significantly fewer participants who experienced any adverse event (56% vs 34%, respectively) and fewer overall adverse events (64% vs 34%, respectively; P =.047). In addition, the EFV group had a significantly higher incidence of adverse events of the central nervous system (41.5% vs 5.3%; P <.001). There was no significant difference between the EFV and RAL groups in the number of participants who experienced serious adverse events (10% vs 13%, respectively) and each group had a total of 8 serious adverse events (P =.731). Further, death from tuberculosis occurred in 3 participants in the EFV group and 2 in the RAL group and a total of 18 participants developed AIDS (9 in each groups); there was no statistically significant difference in time to AIDS/death (P =.94) in either group.

Overall, the study authors concluded that, “Our study supports the 2019 WHO guidelines which recommends moving away from efavirenz-based 1st-line ART.”

Reference

Le T, Chau NV, Thao VP, Ly VT, Thanh NT, Thu NT, Paul R, Ndhlovu L, Chow D, Shikuma C. (2020, March). A randomized controlled trial of raltegravir vs. efavirenz-based ART in HIV-HCV coinfection. Poster presented at: CROI 2020; March 8-11, 2020; Boston, MA. http://www.croiconference.org/sites/default/files/uploads/croi2020-program-and-information-guide.pdf. Accessed March 27, 2020.