HAART alone is not enough for treatment of moderate-severe KS

Individuals with moderate or advanced Kaposi’s sarcoma (KS) have much higher rates of partial or complete remission of lesions when highly active antiretroviral therapy (HAART) is combined with the liposomal chemotherapeutic agent, pegylated liposomal doxorubicin (PLD; Caelyx) than with HAART alone, according to a letter by Spanish researchers in the most recent issue of the journal AIDS. This is the first randomised study to assess the direct effect of HAART on HIV-related KS regression, and suggests that, unlike previous studies, HAART alone is not sufficient when KS is moderate or severe.

Twenty-eight individuals, the majority of whom were gay men with a median age of 40, a median CD4 count of 97 cells/mm³ and median viral load of 39,800 copies/ml were randomised into two groups. All participants had at least ten cutaneous KS lesions or mucosal or visceral involvement, and patients with life-threatening KS were excluded. The only statistical difference between the two randomised groups was the prevalence of previous opportunistic infections, which was higher in the group treated with both HAART and PLD.

After 48 weeks, when two patients in each group were lost to follow-up, complete or partial remission was observed in ten of the 13 (76%) on HAART and PLD and three (20%) on HAART alone. The use of PLD was the only factor found to be related to response to treatment in multivariate analysis (odds ratio = 27, 95% confidence interval [CI]: 2.3 - 307; p = 0.008).

Additionally, ten of the patients in the HAART alone group had to be rescued with PLD during the study, due to the clinical progression of their KS. In seven, tumour progression occurred during the first three months on HAART, prior to an increase in CD4 counts. However, in two, a delayed progression was seen, after HAART reduced viral load and increased CD4 counts, and the researchers concede that this may have been due to immune recovery syndrome (IRIS).

In total, 23 patients received at least one 20mg/m² three-weekly cycle of PLD, 13 in the HAART/PLD arm and ten in the HAART only group. One third of the patients experienced at least one treatment-related adverse event, the most common being anaemia and neutropenia. All events were mild, however, and treatment was not interrupted, although three individuals needed dose reductions of PLD. Two patients died whilst receiving PLD, but their doctors found neither KS nor PLD to be contributing factors.

Although previous studies have found that HAART alone was sufficient for an improvement in KS symptoms, the authors point out that “most of these studies included few patients, with less advanced KS, were not randomised, and mixed patients treated with KS alone with patients treated with specific KS therapy plus HAART.”

In conclusion, the authors say “although HAART alone may be enough for patients with less advanced KS, in cases of moderate-severe disease better response rates are observed when PLD is given with HAART.”