CD4-guided treatment interruptions safe and cost-effective, Thai study shows

The final results of a small Thai study have shown that using CD4 cell counts to guide treatment interruptions is a safe way to reduce the time on therapy - and its cost - while maintaining good virological and immunological responses. These findings were presented today at the Fifteenth International AIDS Conference in Bangkok.

The HIV-NAT 001.4 study was designed to assess the safety, efficacy and outcome of structured treatment interruptions in Thai patients, comparing patients taking therapy continuously with those on a fixed week on-week off (WOWO) regime and a third group using CD4 cell counts to guide treatment breaks.

The investigators recruited 74 treatment-experienced HIV-positive patients, who were given hard-gel saquinavir boosted with ritonavir (1600/100mg once daily) and two nucleoside analogues until they had had viral loads below 50 copies/ml and CD4 cell counts above 250 cells/mm³ for at least six months. The patients were then randomised to the three study arms and monitored regularly for 96 weeks, although the WOWO arm was terminated at 72 weeks since half of the patients in this arm were experiencing virological failure.

Patients in the CD4-guided arm stopped therapy at the start of the trial and remained off treatment until their CD4 count fell below 350 cells/mm³, or 30% below baseline. Treatment was stopped again whenever the three-monthly CD4 cell count had risen above 350 cells/mm³ or 30% above baseline. After 96 weeks of interrupted therapy, the patients in this arm were given twelve weeks of continuous therapy with the same saquinavir-based regimen, so that the final endpoint of the trial at 108 weeks did not fall within any patients’ interruptions.

At the end of the 108 weeks of follow-up, 24 (96%) of the patients in the continuous therapy arm had CD4 cell counts above 350 cells/mm³, as did all 23 patients in the CD4-guided arm. However, while the median CD4 cell count remained constant across the trial in the continuous arm, in the CD4-guided there was a significant fall from 766 cells/mm³ at baseline to 439 at 96 weeks and 488 at 108 weeks (p

Although the proportion of patients with viral loads below 400 copies/ml was similar in the two arms (100% vs. 96%), more patients in the continuous arm had viral loads below 50 copies/ml (96% vs. 59%). Dr. Jintanat Ananworanich, presenting, pointed out that the lower value in the CD4-guided arm was due to five patients having high viral loads at week 96, that would have taken more than 12 weeks of continuous therapy to reduce to below 50 copies/ml.

Omitting these five patients’ viral loads, she claimed that 17 of the remaining patients (94%) had viral loads below 50 copies/ml, a value that was not significantly different to the continuous arm. In both arms, the one patient failing to achieve an undetectable viral load did so following poor adherence to the drug regimen.

Importantly, Dr. Ananworanich showed that there were no differences in HIV-related illnesses, adverse events, blood lipid levels or quality of life scores between the two arms of the study, suggesting that the CD4-guided regimen is safe and well tolerated. However, the time spent on HAART was reduced in the CD4-guided group by 54%, potentially slashing the cost of antiretroviral treatment while maintaining good control of HIV replication and CD4 cell counts that are only slightly inferior to those from continuously-treated patients.

In response to a question from audience member Dr. Irene Adams, the presenter stated that CD4-guided treatment strategies are likely to be cheaper than continuous therapy, despite the cost of more frequent CD4 cell counts. Although the efficacy of the regimen was not studied beyond two years in this study, she concluded by saying that CD4-guided interruption strategies are likely to be a safe and cost-effective option for HIV treatment in resource-limited settings such as Thailand.