HAART has led to a dramatic reduction in KS incidence in Europe

The incidence of the AIDS-defining cancer Kaposi’s sarcoma (KS) has fallen significantly in Europe since the introduction of HAART, according to a prospective cohort study published in the June 15^th edition of Cancer, which is now available on-line. The investigators from the EuroSIDA study found that only 1% of patients who commenced treatment with HAART developed KS, and that the main risk factor for the development of KS was a poor immunological response to HAART. However, KS has not gone away, they report; around 6% of people diagnosed with AIDS still have KS.

In the pre-HAART era, KS accounted for 20% of all initial AIDS diagnoses in Europe. Diagnoses were mainly made in gay men. A reduced incidence of the malignancy was, however, being reported even before the introduction of HAART. Since HAART became widely available, individuals, clinics and national cohorts have reported a dramatically reduced incidence of KS, but these reports have often been limited by the small number of patients involved.

Accordingly, investigators from the EuroSIDA cohort study conducted a prospective cohort study looking at the incidence and risk factors for the development of KS in a study population of over 7,000 individuals drawn from 72 HIV treatment centres across Europe (and from Argentina and Israel) between 1994 and 2002.

Results were stratified according to time period, with 1994-95 classified as pre-HAART, 1996-97 as early-HAART and 1998 onwards as late-HAART. Changes in the incidence of KS were also compared to trends for other AIDS-defining cancers and infections.

Individuals were followed from the date of their recruitment to the cohort to the development of KS or until the last follow-up visit. The incidence of KS was calculated per 1000 patient years of follow-up (PYFU). The investigators included in their analysis factors such as CD4 cell count, viral load, other AIDS-defining illness, anti-herpes therapy, and demographic variables.

A total of 567 individuals had KS at the time of their recruitment into the cohort. These individuals were more likely to be male, gay men, and from northern Europe (p<0.0001).

However, the investigators found that the prevalence of KS in newly recruited patients declined over time from 7.9% of individuals who joined EuroSIDA pre-HAART to 2.2% of patients in the late-HAART era (p<0.001).

Individuals with KS at recruitment had significantly lower CD4 cell counts (103 cells/mm³ versus 245 cells/mm³), were significantly older (39 years versus 36 years) and were recruited to EuroSIDA earlier (P<0.0001 for all comparisons). Viral load, however, was similar between those who had KS at baseline and those who did not.

The incidence of KS declined from 24.7 cases per 1000 PYFU in 1994 to 4.7 per 1000 PYFU in 1997 and 1.7 per 1000 PYFU in 2002. This provided an estimated annual reduction in the incidence of KS of 39%. In any given year, KS was responsible for between 4.1%-7.5% of AIDS diagnoses and this did not change significantly over time.

The rate of the decline in the incidence of KS was significantly higher than that seen for the AIDS-defining cancer non-Hodgkin’s lymphoma.

A total of 4,014 individuals started HAART during the study period. A total of 41 (1%) of these individuals developed KS. Patients who developed KS after starting HAART had lower CD4 cell counts (median 77 cells/mm³ versus 210 cells/mm³, p<0.0001), higher viral loads (median 150,000 copies/ml versus 15,000 copies/ml, p<0.0001), and had lower nadir CD4 cell counts (p=0.003) and higher pre-HAART viral loads (p=0.042).

Investigators also found that when an individual did develop KS, they were more likely to do so within six months of starting HAART and to have experienced a poor CD4 cell response to HIV treatment (p<0.0001). Individuals who developed KS whilst taking HAART were also more likely to have a viral load above 400 copies/ml after six months of treatment (p=0.029).

In multivariate analysis, patients taking HAART with higher current CD4 cell counts (p<0.0001) were found to be less likely to develop KS. It was also established that the risk of developing KS decreased with duration of HAART (p=0.037). Gay men were significantly more likely to develop KS than individuals from other risk groups (p=0.050).

Similarities between the risk factors for the development of KS in the pre- and post-HAART eras were noted by the investigators. These included low CD4 cell counts, male sex, and residence in northern Europe versus southern Europe residence. The investigators speculate that the differing geographical distribution could be due to local prevalence of HHV-8.

”We observed an overall decrease of 39% in the incidence of KS since 1994… among patients receiving HAART there remains an increased risk of KS for homosexual men and for patients with low CD4 counts,” comment the investigators.

They conclude, “we have demonstrated a sizeable decrease in the incidence of KS among European patients with HIV, despite the finding that KS continues to represent the AIDS-defining condition in approximately 6% of all AIDS diagnoses. Most patients who developed KS whilst receiving HAART had low CD4 counts at the start of treatment and developed KS within six months of the initiation of HAART. A greater incidence of KS among homosexual men continues to be observed, as does a significantly reduced incidence of KS among patients with relatively high current CD4 counts.”