Two studies of immune-boosting therapies offer new prospects of delaying AIDS for resource poor countries, and new treatment options for people in the developed world who want to avoid taking HAART.
A lengthy follow up of participants in a Thai trial of Remune, a therapeutic vaccine made from HIV which has been killed and stripped of its ability to enter cells, shows that even in the absence of antiretroviral therapy, three-monthly injections of the vaccine are associated with stable viral load and rising CD4 counts.
Twenty-seven individuals who participated in the original placebo controlled trial of Remune have continued to receive Remune as an open label treatment for 136 weeks, without antiretroviral therapy, and still have viral load below 10,000 copies. In the same period the mean CD4 count of the group has increased by an average of 100 cells to over 500 cells/mm3.
Amongst a larger group from the original study who have been followed for 88 weeks, only 9 out of 68 have experienced a viral load increase greater than 0.5 log. Twenty of 68 have experienced a viral load decrease of greater than 0.5 log during the same period, whilst the remaining 39 have not experienced significant viral load changes during the study. The average CD4 increases according to viral load change were +10 cells/mm3, +30 cells and +60 cells respectively.
Meanwhile, Dr Mike Youle of the Royal Free Hospital has reported that people treated for an average of one year with bimonthly five day cycles of interleukin-2 have maintained stable viral load without the need for any antiretroviral therapy.
The study, which recruited 36 patients with CD4 counts above 350, was designed to test whether interleukin-2 could be safely used to boost CD4 cell numbers without causing large increases in viral load. Previous studies of interleukin-2 have reported spikes in viral load during the treatment cycle even when viremia is partially controlled by antiretroviral drugs.
Participants were randomised to receive either 4.5 million or 7.5 million i.u. of interleukin-2 as a subcutaneous injection every day for five days, bimonthly, or to join a control group. They were allowed to discontinue the dosing cycles if CD4 increases were satisfactory or side-effects unacceptable,
After 64 weeks there was no significant difference in viral load between the two groups, although the size of the study was such that the viral load difference between the two groups would need to be greater than 0.7 log for researchers to be certain that the two groups genuinely differed in their response to treatment.
The CD4 cell increase in IL-2 group averaged 148 cells, versus 25 cells, and this difference was statistically significant. Some individuals had CD4 increases of greater than 900 cells, but in general the CD4 increase was lower than that seen when the immune booster is used with HAART. However, Dr Youle asked, “Is there a functional difference between having a CD4 count of 600 and 900?”.
Only one individual experienced a viral load increase greater than 1log whilst on treatment, and Dr Youle said that this patient experienced a return to pre-treatment viral load levels when treatment stopped.
Side effects such as fever, nausea, headaches and muscle pain were more severe with the 7.5 million i.u. dose, and there was no difference, said Dr Youle, between CD4 cell responses to the two doses.
“We need to investigate ways of reducing side effects if this is to be a realistic treatment for people currently in work” said Dr Youle, “but it’s certainly going to be attractive for patients who do not want to take antiretrovirals at high CD4 counts, and most don’t”.
The study was part of the preparations for the international Vanguard study. Further steps in exploring the use of IL-2 as an immune booster without HAART are still unclear, but Dr Youle regards the UK study as proof of concept.
He also told aidsmap that the cost of producing interleukin-2 could be brought down dramatically.
“Recombinant IL-2 is dirt cheap to synthesise and could be a serious option for developing countries. I’m keen to see larger studies in developing countries.”
Churdboonchart V et al. Results of the follow-up study on 297 asymptomatic HIV-infected subjects previously enrolled in the Phase II double-blind, adjuvant-controlled trial of HIV-1 immunogen (Remune) in Thailand. Thirteenth International Conference on AIDS, Durban, abstract LbOr26, 2000.
Youle M et al. Randomised study of intermittent subcutaneous interleukin-2 (IL-2) therapy without antiretrovirals versus no treatment. Thirteenth International Conference on AIDS, Durban, abstract LbOr27, 2000.