Boosted saquinavir monotherapy explored as treatment option for patients with advanced HIV in South Africa

Monotherapy with the protease inhibitor saquinavir boosted by ritonavir provides safe antiretroviral induction therapy for individuals with advanced HIV disease, according to a small South African pilot study reported in the January 28^th edition of AIDS. The investigators noted that treatment with saquinavir/ritonavir achieved a significant increase in CD4 cell count, a significant fall in viral load, and an improvement in anaemia, neutropenia, and liver function and note that the safety and efficacy of this treatment strategy is being explored in randomised controlled studies.

Many South African HIV patients first attend for medical care when they are already ill because of HIV and have severe immune suppression. Treatment with a HAART regimen including two NRTIs and an NNRTI may not be initially tolerated by these individuals due to underlying anaemia, neutropenia, and abnormal liver function.

Investigators wished to evaluate the use of a short-course of saquinavir/ritonavir induction therapy before the use of an NNRTI-containing HAART regimen in these patients.

In a retrospective study, data for 28 HIV-positive treatment-naïve patients who had a CD4 cell count of below 150 cells/mm³ were assessed. These patients were judged to have HIV disease that was too advanced to tolerate conventional HAART.

Treatment consisting of saquinavir/ritonavir 600/100mg twice daily was provided for between four and eight weeks. This dosage was chosen due to low baseline body weight. The duration of treatment was determined by the individual patient’s ability to pay for therapy. At baseline, four weeks, and eight weeks CD4 cell count and viral load was measured. HIV disease progression, side-effects, and clinical chemistry were also assessed at weeks four and eight.

Of the 28 patients included in the study, 15 (54%) were men, and the median age was 33 years. All were of African race. The median body weight at entry to the study was 60kg, median CD4 cell count was 26 cells/mm³, and median viral load was 320,000 copies/ml. Baseline haemoglobin, neutrophils, and liver function were abnormal in a “proportion of patients.”

All 28 individuals completed between four and eight weeks of saquinavir/ritonavir monotherapy. The median increase in CD4 cell count was 115 cells/mm³, and viral load fell to a median of 1000 copies/ml. In addition, ten patients (36%) achieved a viral load of below 400 copies/ml.

The most commonly reported side-effects were gastro-intestinal, but these tended to be mild and occurred most frequently during the first two weeks of therapy. Small increases in haemoglobin, neutrophilis and in liver function were noted during the treatment with saquinavir/ritonavir.

Patients were switched to an NNRTI-containing HAART regimen. After an additional two years of follow-up 26 individuals remained economically active, the other two patients having developed MAI.

“This strategy of boosted PI induction may allow time for initial recovery of CD4 cell counts with a lower risk of haematological toxicity or liver enzyme elevations, which could otherwise limit the safety of initial treatment with NRTI/NNRTI-based HAART”, write the investigators.

However the investigators note that there are concerns about the safety of using boosted protease inhibitors in monotherapy, and conclude “despite the potential safety advantages of sparing NRTI, there is also the potential risk of virological failure or the development of primary PI resistance. New randomised clinical trials are evaluating the efficacy and safety of boosted PI monotherapy relative to conventional NRTI/NNRTI-based HAART for treatment-naïve patients.”