Risk of Kaposi sarcoma during the first months on combination antiretroviral therapy

Abstract

Objective Determine if incident AIDS-defining Kaposi sarcoma (KS) or Pneumocystis jiroveci pneumonia (PJP) is associated with combination antiretroviral therapy (cART) initiation. Design Compare risk for KS and PJP by time on cART and CD4 reconstitution. Methods In the FHDH-ANRS CO4 cohort (N=66,369), KS (N=1811) and PJP (N=1718) incidence rates were computed by demographic and HIV strata. Crude and adjusted relative risk (RR) with 95% confidence intervals (CI) following cART initiation were calculated by Poisson regression with untreated patients during 1996–2009 as reference. CD4 counts were compared by Wilcoxon rank sum tests. Results KS risk was very high during months 1–3 on cART (N=160, RRCrude 3.94, CI 3.26–4.76), which was incompletely attenuated by adjustment for demographics and contemporaneous CD4 count (RRAdj 1.25, CI 1.02–1.53). Corresponding PJP risk was minimally elevated (N=84, RRCrude 1.80, CI 1.42–2.30) and markedly reduced with adjustment on the same variables and PJP prophylaxis (RRAdj 0.52, CI 0.41–0.67). HIV load had no added effect. Median CD4 cell count at cART initiation was much lower in patients with incident KS (82/mm3) or PJP (61/mm3) within 3 months compared with those without (>250/mm3). Notably, median CD4 change was +44 cells/month with incident KS within 3 months of cART initiation versus 0 cells/month with incident PJP (P=0.0003). Conclusions Failure of CD4 reconstitution during months 1–3 on cART fully accounted for incident PJP. In contrast, there were 1.6 additional KS cases per 1000 person-years during months 1–3 on cART, suggesting that immune reconstitution may contribute to the risk for AIDS-defining KS.

Variation in Cancer Incidence among Patients with ESRD during Kidney Function and Nonfunction Intervals

“…11,12 As we demonstrate for the first time, the human papillomavirusrelated cancers (oropharyngeal, anal, cervical, and other genital cancers) had incidence patterns less distinctly associated with transplant intervals. After a human papillomavirus infection, immunosuppression is thought to increase the likelihood that the infection becomes persistent instead of being cleared.…”

AIDS-Related Kaposi’s sarcoma and Associated Immune Reconstitution Inflammatory Syndrome

“…It seems to exist an increased risk of SRI-SK in KS patients with lower median baseline CD4 [11,12], rapid increase in CD4 counts during the initiation of HAART [13], high HIV viral load [8], associated edema [13], clinical pretreatment of KS, detectable plasma HHV8 DNA and hematocrit <30% [8]. The risk of IRIS-SK is similar among different antiretroviral drug regimens [11] although Bower et al [13] reported a higher risk in those patients performing both major HAART classes together, protease inhibitors and non-nucleoside reverse transcriptase inhibitors, in a single regimen.…”

“…Therefore, they speculated that KS-IRIS is somewhat different from other forms of KS and therefore unique management strategies may be considered. Also, further studies on the mechanism of IRIS-SK are necessary as the response of HAART against HHV8 and AIDS-KS requires at least six months and, despite of this, the period of greatest risk of developing IRIS-SK is during the first 3 months of HAART [11].…”

“…The risk of IRIS-SK is similar among different antiretroviral drug regimens [11] although Bower et al [13] reported a higher risk in those patients performing both major HAART classes together, protease inhibitors and non-nucleoside reverse transcriptase inhibitors, in a single regimen.…”

Kaposi Sarcoma in HIV Infected Patients

“…A recent study has reported a high incidence of Kaposi sarcoma during the first 3 months of ART, describing KS as one of the manifestations of immune reconstitution inflammatory syndrome (IRIS) [ [12]. In our study, the median time from ART initiation to KS diagnosis was 5 months (IQR 0-39); roughly half of our patients who were on ART (10/19) were in virological failure at the time of KS diagnosis and in the other 9/19 patients KS could have been an IRIS manifestation.…”