Anti-HIV treatment may be key to treating KS

While chemotherapy may help in improving cases of Kaposi’s sarcoma, effective anti-HIV therapy seems to be needed to fully resolve cases of the disease, say US researchers in the May 11^th edition of AIDS. Yet, these treatments provide less than optimal results, they say, with their study showing only half of cases being effectively resolved.

Kaposi’s sarcoma (KS) characterised by small pink or purple lesions on the skin, was once the most commonly diagnosed cancer among people with HIV. KS strikes when the immune system is severely suppressed and, if it affected the internal organs, was often fatal in the era before effective anti-HIV therapy. The introduction of potent anti-HIV combination therapy in the mid-1990s led to a dramatic decrease in the number of cases of KS and another non-Hodgkin’s lymphoma, another AIDS-related cancer. In fact, a recent US study reported that non-AIDS-related cancers now outweigh AIDS-related cancers in people with HIV.

While it is clear that anti-HIV treatment has reduced the incidence and prevalence of KS, likely through improved immune function, its role in treatment is not clear. This question is of particular relevance to people with HIV living in the developing world, where KS remains a relatively common condition. There are an estimated 57,000 cases in sub-Saharan Africa alone.

To assess the role of anti-HIV drugs in treating KS, investigators at the University of Washington performed a retrospective analysis of patients with KS seen at university clinics between January 1996 and December 2005. The cohort comprised 64 patient records: all were men, and the median age was 38 years. Indicative of advanced HIV disease at diagnosis, median CD4 cell count was 40 cells/mm³ and median viral load was 100,000 copies/ml.

Investigators categorised cases as no change/progression, improvement or resolution. Improvement was scored as KS lesions improved and no new lesions developed. Resolution was scored as no sign of KS lesions upon physical exam. Records were also examined to note if and when HAART and chemotherapy were initiated.

Of patients showing improvement, 75% received HAART and 42% received chemotherapy, almost exclusively with liposomal doxorubicin, an anti-cancer drug used in the treatment of ovarian and breast cancers and AIDS-related KS. Of patients showing resolution, 83% received anti-HIV treatment and 50% received chemotherapy.

Over the ten years of the study, anti-HIV drug choice followed historical prescribing trends: during the late 1990s, regimens contained a protease inhibitor such as nelfinavir; in the early 2000s, non-nucleoside reverse transcriptase inhibitors, especially efavirenz, were favoured; and from 2004 to 2006, boosted protease inhibitors such as atazanavir/ritonavir were frequently used.

During a 36-month follow-up period, 77% of records showed an improvement in KS disease and 51% showed resolution of the disease. Average time to improvement was nine months, longer than that seen in other clinical trials. The investigators suggest that in a clinical setting, such as in this study, toxic treatments such as chemotherapy may be delayed in less severe cases and that this delay may lead to the observed delay in response.

More striking, the investigators write, is the low overall resolution rate. “Our findings suggest that even in the era of extremely effective therapy for HIV infection and wide availability to chemotherapy, Kaposi's sarcoma remains a persistent disease.”

The investigators went on to analyse the data for predictors of treatment success. In univariate analysis the only baseline characteristic associated with improvement and resolution was lower viral load. The clinical characteristics of stage of KS disease, CD4 cell count and prior use of anti-HIV treatment were not linked to improved outcomes. Lack of a link between disease stage and response is uncommon in cases of cancer but is consistent with findings from other studies of KS.

When assessing the impact of treatment, investigators found that treatment with anti-HIV treatment or chemotherapy was associated with improvement of the disease, with improvement being 4.1 times more likely among patients receiving anti-HIV drugs and 5.5 times more likely among those receiving chemotherapy using multivariate analysis. However, only anti-HIV treatment remained significantly associated with resolution of the disease, with patients on anti-HIV therapy being 6.2 times more likely to resolve the disease.

In comparing different anti-HIV treatment regimens, the investigators found improvement or resolution was not significantly different between non-nucleoside reverse transcriptase inhibitor-based, protease inhibitor-based and boosted protease inhibitor-based regimens. Improvement was 2.7 times more likely among patients receiving boosted regimens than among those receiving unboosted protease inhibitor regimens, but the finding did not reach statistical significance (p = 0.08)

In interpreting these results, the investigators state, “Recent HAART [highly active antiretroviral therapy] use was the only factor associated with resolution and both HAART and chemotherapy were independently associated with improvement, suggesting that introduction of either HAART or chemotherapy can induce initial response to Kaposi sarcoma disease, whereas only HAART was associated with complete resolution of the disease.”

The investigators acknowledge that during the follow-up period, 23% of patients died. Since death was likely not independent of response, this may have inflated the response rates, they write. The study lacked statistical power to address this question and the investigators finish by calling for further study and improved statistical analyses to eliminate some of the confounding factors present in their study.