VANCOUVER, B.C. _ Triple-drug antiviral therapy reduces viralload in the blood of HIV positive adults to undetectable levels. Thisis the major finding of several recent clinical trials, and one of thereasons why delegates left the XI International Conference On AIDSwith optimism that this devastating disease can be beaten.
Early data from clinical trials seem to suggest that triple therapyusing two nucleoside reverse transcriptase inhibitors together with aprotease inhibitor may erect an antiviral barrier capable of providinglong-lasting suppression of measurable viral replication. This, in turn,should boost the immune system in HIV positive individuals.
Speaking on the final day of the meeting, Roy Gullick, of New YorkUniversity Medical Center, presented preliminary data from anongoing study that is following 90 adult, HIV-positive patients, out ofan original 97 who were initially enrolled.
The patients were randomized to receive either the three-drugcocktail Epivir (3TC) plus Retrovir (AZT) and the protease inhibitorindinavir, or Epivir plus Retrovir, or indinavir alone.
Gullick reported that at the start of the study the median HIV RNAlevel of the patients was 41,130 copies/ml and the median CD4 cellcount was 142 cells/mm3. Results of therapy showed that between 80and 90 percent of patients on the triple-drug therapy had their viralRNA levels reduced to undetectable levels (<500 copies/ml) and asustained rise of CD4 cell counts in the range of 100-120 cells/mm3.These effects were maintained throughout the 48 weeks of treatmentso far reported.
In contrast, the study found that less that 20 percent of the patientsreceiving the AZT and 3TC combination ever achieved the PCRassay detection level of <500 copies/ml; and this number fell to lessthan 5 percent by the end of the reporting period. For the indinavirmonotherapy, 40 percent of patients had their viral load reduced toundetectable levels.
While Gullick was quick to point out that the results were stillpreliminary, and they continue to monitor the patients, he indicatedthat because of the dramatic changes in the viral loads and CD4counts observed in patients on the triple-drug regime, the studyprotocol has been amended to allow all patients to receive the three-drug combination therapy.
Besides the now familiar nucleoside reverse transcriptase inhibitors_ 3TC and AZT _ a new reverse transcriptase inhibitor may soon beavailable in the clinical arsenal for use against HIV. Dubbed1592U89, under development by Glaxo Wellcome plc, of Middlesex,U.K., it appears that the compound has a significant effect.
The company presented details of a study that evaluated the effects ofdifferent doses of 1592U89 given alone for four weeks followed byeight weeks in combination with either AZT, or a placebo.
Results from the small Phase I/II trial, involving 80 patients, showedthat at four weeks, treatment with 1592U89 decreased the amount ofviral DNA in the blood by almost 99 percent and improved CD4counts by between 79 and 127 cells/mm3. Following eight moreweeks of treatment, in which patients received either 1592U89 plusAZT or 1592U89 plus placebo, the reductions in viral load andincreases in CD4 cell counts were maintained.
The use of combination therapy is one of the "building blocks" offuture conferences, said Michael O'Shaughnessy, a conference co-chairman. "In medical circles, the optimism and excitement come notfrom any specific discovery but from the many exciting advances inhow the HIV virus functions and thus, how it may be controlled," hesaid.
The next International AIDS Conference will be held in Geneva inJune 1998. n
-- Peter Winter Special To BioWorld Today
(c) 1997 American Health Consultants. All rights reserved.