Combination of indinavir/AZT/3TC still effective for majority of patients at 6 years, says US study

A HAART regimen comprising indinavir, 3TC and AZT is still being taken by a majority of patients enrolled in a study into the combination`s safety and efficacy six years later, according to US research published in the November 7^th edition of AIDS. Investigators also established that the combination was continuing to suppress HIV viral load to below 500 copies/mL in a clear majority of patients, and to below 50 copies/mL in a little under 50% of individuals.

This is the second study to be published in recent weeks showing the long-term effectiveness of HAART. In early October a study was published in The Lancet showing a sustained and dramatic fall in morbidity and mortality in HIV-positive individuals since the introduction of effective anti-HIV therapies in 1996/97 (see link below).

Investigators from several US HIV treatment centres analysed six year follow-up data on 33 individuals. They wished to establish the proportion of patients with viral load below 500 copies/mL and 50 copies/mL, as well as the number of patients who had experienced treatment failure. Data were also gathered on treatment switches, changes to CD4 cell count, and the incidence of side-effects, including lipodystrophy.

To be included in the study patients had to have had previous experience of AZT therapy for at least six months, have an HIV viral load above 20,000 copies/mL and a CD4 cell count between 50 and 400 cells/mm³. On entry to the study, AZT resistance mutations were present in 25 of the 32 individuals (32%).

Patients were assessed at regular clinic visits throughout the study period. Individuals who left the study were assessed using a questionnaire, which included items on the last antiretroviral regimen taken, approximate viral load and CD4 cell count at year five/six, and if applicable the date and cause of death.

Of the 33 study members, 16 (48%) discontinued treatment with the trial combination before six years of follow-up. Data were obtained for twelve patients who stopped taking the study combination before six years. Of these, seven changed therapy because of an increase in their viral load, two because of the use of contraindicated medications to treat AIDS-defining illness, one because of side-effects, and two individuals switched medication after requesting it.

No patient died whilst taking the study medication. Three patients did, however, die after leaving the study, one individual from disseminated Kaposi’s sarcoma, one from a heart-attack, and one from unknown causes.

At year six, 53% of study members for whom data were available had a viral load below 500 copies/mL, and 47% had a viral load below 50 copies/mL. A total of ten patients experienced virological failure, six in year one, three in year three and one in year six. By year six the median CD4 increase from baseline was 268 cells/mm³.

Kidney stones were the most frequently reported side-effect with 14 of the 33 study members experiencing this adverse event at least once during the study period.

Body fat changes of abnormal blood lipids were present in the majority of patients who remained on study medication to the end of six-years of follow-up. Of these 17 patients, ten (59%) were classified as having lipodystrophy.

The investigators conclude, “we showed that the majority of HIV-infected subjects originally randomised to indinavir, [AZT and 3TC] had sustained suppression of HIV-1 viremia and CD4 cell increases over 6 years.?If study discontinuations were excluded from this analysis, then the proportion of patients with viral suppression at six years increased to 80%. Nevertheless, the investigators believe that studies into the long-term effectiveness of HAART should be conducted according to strict criteria and include all patients originally enrolled in the study, regardless of their later treatment history.

Further information on this website

HAART continues to improve survival, but not all HIV risk groups benefit equally - news story