A new fusion inhibitor that prevents HIV
entry into cells showed potent antiviral activity in early clinical studies and
has a long half-life, suggesting it may be suitable for once-weekly dosing,
Chinese researchers reported yesterday at the 52nd Interscience
Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in San Francisco.
Multidrug-resistant HIV remains a concern, especially for highly
treatment-experienced people who have used most types of antiretroviral drugs.
Fusion inhibitors – which prevent HIV from fusing with T-cell membranes to allow
cell entry – may remain active against virus that has developed resistance to
commonly used drug classes.
The sole approved fusion inhibitor, enfuvirtide (Fuzeon, formerly known as T-20), must be
administered by subcutaneous injection twice daily, leaving much to be desired
in terms of convenience and ease of use.
Albuvirtide (FB006M), a synthetic peptide being
developed by Chongqing
Frontier Biotechnologies, is chemically related to enfuvirtide, and also
works by binding to the HIV gp41
envelope protein. The new drug binds strongly to the human blood protein
albumin, however, which enables it to last longer in the body but makes it
unable to penetrate into the brain or testicles.
In preclinical in
vitro and in vivo studies,
albuvirtide demonstrated potent activity against a broad spectrum of HIV
isolates and had a favourable safety profile.
Researchers at ICAAC presented results from two clinical
trials of albuvirtide monotherapy in previously untreated people with HIV in
The first was a phase I proof-of-concept single-dose
escalation trial. A total of 55 participants were randomly assigned to receive single
doses of albuvirtide ranging from 20mg to 640mg, or placebo. The drug was
administered by intravenous infusion and participants were hospitalised for
observation. All but one were treated and analysed, and two discontinued
About 70% of participants were men and the median age
was 38 years. The median HIV viral load was approximately 20,000 copies/mL, the
median CD4 cell count at study entry was about 400 cells/mm3 and
all had at least 250 cells/mm3.
Albuvirtide was generally safe and well tolerated at
all doses tested. No serious adverse events or injection site reactions were
The drug had a good pharmacokinetic profile. The
plasma half-life was eleven days, with a linear elimination pattern. Antiviral
activity continued for six to ten days after a single dose.
The second study was a phase IIa open-label trial of single
and multiple doses of albuvirtide. This study included twelve treatment-naive
participants assigned to receive either 160mg or 320mg albuvirtide. They
received the drug once daily for the first three days, followed by two
once-weekly administrations at days 8 and 15.
All participants in this study were gay men. There
were some baseline differences between the dose arms. In the 160mg arm the
average age was 36 years, the median HIV RNA level was about 30,000 copies/mL
and the median CD4 count was 484 cells/mm3. In the 320mg arm, the
average age was 27 years, the median viral load was about 8,000 copies/mL and
the median CD4 count was 406 cells/mm3.
was found to be safe and well tolerated with no serious adverse events,
drug-related side-effects or injection-site reactions. Participants did not
develop detectable antibodies against the drug after multiple
In the 160mg arm viral load declined by 0.68 log10
copies/mL on average and HIV RNA fell to 0.5 log10 or less in 83% of
participants. In the 320mg arm, the mean viral load decrease was 1.05 log10
copies/mL and 100% reached 0.5 log10 or less.
There was a significant dose-response relationship
between albuvirtide plasma concentration and viral load suppression. While
sustained viral suppression was seen after the first three days of dosing, HIV
RNA rebounded more rapidly after the later once-weekly doses, a possible
indicator of drug resistance.
The researchers concluded that albuvirtide produced
good viral suppression with a clear relationship between dose and antiviral
efficacy. The eleven-day half-life supports once-weekly dosing, they added. Further
studies are planned using albuvirtide in combination antiretroviral regimens.