Compiled & edited by Robert Fieldhouse
New international guidelines on how to best use the fusion inhibitor T-20, drawn up by some of the world’s leading HIV clinicians, were unveiled in Paris last month.
T-20 (Fuzeon) is the first of a new class of drugs which block HIV from entering and infecting CD4 cells. It is taken twice daily by injection into body fat.
T-20 has been studied in people with lots of treatment experience and resistance to other antiretroviral drugs. In clinical trials people receiving T-20 were twice as likely to achieve undetectable levels of HIV and experienced double the CD4 count gains over 48 weeks compared to those receiving standard combination therapy alone.
The guidelines recommend that clinicians offer T-20 therapy when the CD4 count is still above 100 cells, rather than wait for it to decline further.
Though T-20 has demonstrated reductions in viral load and improvements in CD4 across a range of pre-treated individuals, (some with extensive treatment experience), the drug works best when a patient is still responsive to “at least two other antiretrovirals, ideally from different classes.”
Resistance testing should guide the choice of these additional antiretrovirals the guidelines said.
Where insufficient options for an effective background exist, T-20 should still be considered, despite the unlikelihood of keeping HIV fully suppressed.
Speaking at the presentation of the guidelines, Dr Mike Youle, of the Royal Free Hospital, London, said: “By providing clear advice on the timing of Fuzeon initiation and patient support during therapy, these guidelines clarify the place of this breakthrough drug in current HIV treatment regimens, and will enable more pre-treated patients to benefit.”
Current British HIV Association guidelines recommend using T-20 following the failure of two treatment regimens.
Three major drug companies are in talks about developing a once daily, three-in-one fixed-dose combination tablet of tenofovir, FTC and efavirenz.
The collaboration was announced in a press release last month jointly issued by Bristol-Myers Squibb Company, Gilead Sciences and Merck & Co.
The talks represent a significant step forward in the battle to simplify therapy and is the first time three major pharmaceutical companies have worked together to develop co-formulated drugs in the field of HIV.
While the new combination pill is in development, the companies are looking at the feasibility of co-packaging the three existing pills.
The collaboration was unveiled just days before the US government said it would expedite approval of co-formulated and co-packaged antiretroviral drugs destined for resource-limited settings.
Gilead Sciences filed for both European and US approval of a single tablet, fixed-dose combination tablet of its NRTIs tenofovir and FTC in March. In the US the co-formulation has been granted ‘priority review’ status. This only happens when a drug addresses an unmet medical need, offering a significant improvement in the safety or effectiveness of treatment, diagnosis or prevention of a serious or life-threatening illness.
It means the drug is likely be licensed in the US in early Autumn. European licensing should follow soon after.
Once formulated, the three-in-one therapy will be evaluated to see if the blood levels of the products when co-formulated are comparable to that achieved when the drugs are dosed separately. This will be swiftly followed by filing for license with the regulatory authorities.
The rate of new cases of the HIV-related cancer Kaposi’s Sarcoma (KS) has declined dramatically since the introduction of HAART in the mid 1990s in Western Europe.
Prior to the widespread use of HAART, KS accounted for about 20 per cent of initial Aids diagnoses in Europe.
Data from more than 7,000 individuals living in Europe as well as Israel and Argentina show that overall KS has declined by 39 per cent since 1994. KS has declined much more significantly than the Aids defining cancer non-Hodgkin’s lymphoma.
Even when using HAART, gay men and people with low CD4 counts appear at increased risk of developing KS.
People on HAART who developed KS most likely did so in the first six months of therapy after experiencing only a marginal increase in CD4 count and not getting an undetectable viral load.
A small study at the US National Institutes of Health (NIH) suggest it may be feasible for people with HIV to take a simple once daily combination in cycles of seven days on, followed by seven days off.
Eight people living with HIV on stable antiretroviral therapy for more than six months switched to weekly cycles of efavirenz, ddI, 3TC. One patient withdrew for personal reasons but the other seven maintained undetectable viral loads for periods ranging between 60 and 84 weeks.
Unlike a previous week-on week-off NIH study which evaluated twice daily antiretroviral therapy, researchers did not observe blips in participant’s viral load during the week off period; nor did they find any evidence of viral resistance.
Randomised, controlled trials of week-on, week-off therapy are underway in the US and other countries. If the strategy is proved safe and effective in a clinical setting, week-on, week-off therapy with well-chosen drugs may prove an important strategy to expand access to antiretroviral therapy in resource-limited settings.
Researchers underlined the need for strict adherence to therapy during the ‘on’ period. It is possible that the once daily combination allows for greater adherence compared to twice daily therapy; improvement to treatment adherence following a switch to once daily therapy has previously been demonstrated among people taking medication for diabetes and hypertension.
London HIV clinics are now able to prescribe the new nucleoside analogue FTC for first-line HIV treatment following price negotiations between the drug’s manufacturer Gilead Sciences and the London HIV Consortium, the body that evaluates which HIV drugs can be prescribed in London.
Licensed late last year, FTC was originally more expensive than its main competitor 3TC which is offered to London clinics at a heavily discounted price. Gilead Sciences has now agreed to match the price of FTC to that of 3TC to every London HIV clinic.
The once daily combination of FTC, tenofovir and efavirenz is currently being studied against the twice daily Combivir and once daily efavirenz, the current gold standard first-line combination, in patients who have never used antiretroviral therapy.
Eagerly anticipated 24-week results of this trial are expected to be presented in the Autumn. Licensing of the co-formulation will follow.
FTC is taken as one pill once-a-day. It is well-tolerated and is also active against hepatitis B.
A new study suggests HAART may slow progression to liver fibrosis in people co-infected with hepatitis and HIV.
Prior to the introduction of new and effective antiretroviral HIV therapies in the mid 1990s, studies of hepatitis C disease progression suggested people co-infected progressed more quickly to liver damage than those who were hepatitis C positive only.
This study from the US and Puerto Rico included 685 patients (297 of whom were HIV-hepatitis C co-infected) who had their liver damage measured by liver biopsy.
A known date for hepatitis C infection was available for 675 individuals. Researchers found no difference in liver fibrosis between the HIV positive and HIV negative participants.
However, people with HIV with a HIV viral load above 400 copies progressed more quickly to fibrosis than both HIV positive people with an undetectable viral load and HIV negative individuals.
It would appear that undetectable viral load provides protection against liver fibrosis in people co-infected with both HIV and hepatitis C.
