Biktarvy may be the best option for people with both HIV and hepatitis B
Two antiretroviral regimens have done a good job of controlling HIV in people living with both HIV and hepatitis B virus (HBV)but the Biktarvy combination pill resulted in greater HBV suppression, according to a study presented at the 24th International AIDS Conference (AIDS 2022) this week in Montreal.
HIV and HBV are transmitted by similar routes, and many people carry both viruses, which is called co-infection. Worldwide, around 8% of people living with HIV also have hepatitis B, but this can be as high as 25% in areas where both viruses are endemic.
“Emerging HIV epidemics in regions with high HBV rates such as Asia are increasing the number of people co-infected with HIV/HBV,” said Anchalee Avihingsanon, MD, PhD, of HIV-NAT and the Center for Thai Red Cross Aids Research.
Over years or decades, chronic hepatitis B can lead to serious liver disease, including cirrhosis, liver cancer and the need for a liver transplant. People co-infected with HIV/HBV tend to experience more rapid progression of liver disease and are at increased risk of serious complications compared to people with hepatitis B alone. On the other hand, a recent study found that people living with both HIV and HBV received better care than those who only had hepatitis B.
Some antiretrovirals used to treat HIV – lamivudine, emtricitabine, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) – are also active against HBV. They are components of several widely used antiretroviral pills. Treatment guidelines recommend that people co-infected with HIV/HBV include these dual-action drugs in their regimen.
Antiviral treatment suppresses HBV replication, which can reduce liver inflammation and return liver enzyme levels to normal. Treatment can sometimes cause the loss of hepatitis B antigens and the production of antibodies (seroconversion), but this is less common. Loss of hepatitis B surface antigen (HBsAg) is considered a functional cure.
Avihingsanon and colleagues conducted a study comparing Biktarvy (bictegravir/TAF/emtricitabine) to dolutegravir plus TDF/emtricitabine (Truvada and generic equivalents) for people co-infected with HIV/HBV. Bictegravir and dolutegravir are two very effective integrase inhibitors against HIV. TAF and TDF are the new and old versions of tenofovir; TAF is gentler on the kidneys and bones, but has been associated with greater weight gain.
The Phase III ALLIANCE trial recruited 243 participants, primarily from Thailand, China or Malaysia, who had never been treated before for HIV or hepatitis B. Most were male, approximately 90% were Asian and the median age was about 32 years old. About 80% were positive for hepatitis B “e” antigen.
At the start of the study, they had an HIV RNA viral load of 500 or more and an HBV DNA viral load of at least 2000. The median CD4 count was quite low, at around 240. Their HIV was not resistant to tenofovir or emtricitabine, and they had adequate kidney function (a criterion for people taking TDF).
Participants were randomly assigned to receive Biktarvy, taken as one pill once a day, or dolutegravir plus TDF/emtricitabine, taken as two pills once a day. The primary endpoint was HIV and HBV viral suppression at 48 weeks, with treatment continuing for 96 weeks.
Both diets were very effective in suppressing HIV, as seen in previous studies of people living only with HIV. At 48 weeks, 95% of people taking Biktarvy and 91% of those taking dolutegravir plus TDF/emtricitabine had an HIV viral load below 50. CD4 cell gains were 200 and 175, respectively.
But HBV suppression was harder to achieve: 63% of people taking Biktarvy and 43% of those taking dolutegravir plus TDF/emtricitabine had HBV viral loads below 29 copies. This was a statistically significant difference in favor of Biktarvy.
Biktarvy was also more likely to improve markers associated with functional cure, although hepatitis B antigen loss and seroconversion were rare in both treatment groups.
Among participants who were HBeAg positive at baseline, 26% in the Biktarvy group experienced HBeAg loss at 48 weeks, compared to 14% in the dolutegravir plus TDF/emtricitabine group. HBeAg seroconversion was also higher in the Biktarvy group, 23% versus 11%, respectively. This latter difference was statistically significant at 48 weeks.
Hepatitis B surface antigen declines were even less frequent: 13% in the Biktarvy group and 6% in the dolutegravir plus TDF/emtricitabine group achieved loss of HBsAg at 48 weeks, and 8% against 3%, respectively, underwent HBsAg seroconversion. Although the rates of HBsAg loss and seroconversion were numerically higher in the Biktarvy group, these differences did not reach statistical significance at 48 weeks.
People taking Biktarvy were more likely than those in the dolutegravir plus TDF/emtricitabine group to experience normalization of ALT liver enzymes (73% versus 55%, respectively), but again the difference was not significant at 48 weeks. Seven and four participants, respectively, experienced ALT flares, flare-ups of liver inflammation that may be a precursor to loss of HBsAg
Treatment was generally safe and well tolerated. The frequency of drug-related adverse events was similar in the Biktarvy and dolutegravir plus TDF/emtricitabine groups (24% versus 27%, respectively), as were serious laboratory abnormalities (34% versus 31%). Serious drug-related adverse events were rare in both groups (5% and 1%).
The most common drug-related adverse event in both groups was weight gain, reported by 6% and 7%, respectively. This is remarkable because in previous studies, TAF has been linked to weight gain and TDF to weight loss. Increases in total and LDL cholesterol were uncommon but observed more often in the Biktarvy group.
Taken together, the results show that Biktarvy is a safe and effective initial treatment for people co-infected with HIV/HBV, Avihingsanon said. Biktarvy was non-inferior to dolutegravir plus TDF/emtricitabine for HIV suppression. Biktarvy was associated with greater HBV suppression and a higher rate of HBeAg seroconversion, with numerically greater but nonsignificant differences in HBeAg loss, HBsAg loss, HBsAg seroconversion, and ALT normalization.
“[HIV/HBV coinfection] is still a very important problem, especially in Asia, and the clinical course of hepatitis B in people living with HIV is marked by an accelerated progression of liver disease,” said the president-elect of the International AIDS Society, Sharon Lewin, MD, of the Peter Doherty Institute for Infection. and Immunity in Melbourne said at an AIDS 2022 press conference. “These are important findings not just for people living with HIV, but for the management of hepatitis B in general.”
Click here to read the study summary.
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