Just over half of highly treatment-experienced patients enrolled in a study of mega-HAART still had viral load below 50 copies/ml after more than two years on the regimen, according to a report from the Royal Free Hospital in London, published this week in the Journal of Acquired Immune Deficiency Syndromes.
Sixty patients with rising viral load were enrolled in the open label study, and had taken a median of two protease inhibitors before joining the study. However, 87% of participants were NNRTI-naïve. The median duration of treatment experience prior to joining the study was 2.9 years (with one quarter having received at least five years of antiretroviral treatment by the beginning of 1998). Sixty per cent of patients had a previous AIDS diagnosis.
Regimens were constructed around efavirenz (taken by all patients), ddI (taken by 73%), hydroxyurea (taken by 73%) and a protease inhibitor (mainly indinavir boosted with ritonavir). Drugs were not chosen on the basis of resistance testing because the study began in early 1998. The median number of drugs included in the regimen was five.
After two years, 31 patients (52%) had viral load below 50 copies, and ten patients stopped therapy altogether. Five individuals died during the study, and a further nine developed an AIDS-defining illness (three cases of lymphoma, two cases of Kaposi’s sarcoma, once case each of PML, PCP, wasting syndrome and oesophageal candida).
Of those on treatment, 72% had viral load below 50 copies after two years, and 72% had experienced CD4 cell increases (in two thirds of cases increases of more than 100 cells/mm3 were observed). The median number of drugs taken remained five after two years.
Multivariate analysis showed that the only factors associated with a reduced chance of viral load below 50 copies and a CD4 cell increase were a higher baseline viral load, and previous NNRTI use.
In this clinic population, patients were given intensive adherence support and preemptive anti-nausea treatment with ondansetron during the first weeks of therapy, together with other aggressive symptom control measures, to ensure that therapy was tolerated.
Youle M et al. Two year outcome of a multidrug regimen in patients who did not respond to a protease inhibitor regimen. Journal of Acquired Immune Deficiency Syndromes 29: 58-61, 2002.