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

ABSTRACT: To determine whether incident AIDS-defining Kaposi sarcoma or Pneumocystis jiroveci pneumonia (PJP) is associated with combination antiretroviral therapy (cART) initiation.Compare risk for Kaposi sarcoma and PJP by time on cART and CD4 reconstitution.: In the FHDH-ANRS CO4 cohort (N?=?66?369), Kaposi sarcoma (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 (CIs) following cART initiation were calculated by Poisson regression with untreated patients during 1996-2009 as reference. CD4 cell counts were compared by Wilcoxon rank sum tests.The risk of Kaposi sarcoma was very high during months 1-3 on cART (N?=?160, RRCrude 3.94, 95% CI 3.26-4.76), which was incompletely attenuated by adjustment for demographics and contemporaneous CD4 cell count (RRAdj 1.25, 95% CI 1.02-1.53). Corresponding PJP risk was minimally elevated (N?=?84, RRCrude 1.80, 95% 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 Kaposi sarcoma (82?cells/?l) or PJP (61?cells/?l) within 3 months than in those who did not develop these conditions (>250?cells/?l). Notably, median CD4 cell count change was +44?cells/?l per month with incident Kaposi sarcoma within 3 months of cART initiation versus 0?cells/?l per month with incident PJP (P?=?0.0003).Failure of CD4 cell count reconstitution during months 1-3 on cART fully accounted for incident PJP. In contrast, there were 1.6 additional Kaposi sarcoma cases per 1000 person-years during months 1-3 on cART, suggesting that immune reconstitution may contribute to the risk for AIDS-defining Kaposi sarcoma.

SUBMITTER: Lacombe JM

PROVIDER: S-EPMC3623279 | biostudies-other | 2013 Feb

REPOSITORIES: biostudies-other

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

Lacombe Jean-Marc JM Boue François F Grabar Sophie S Viget Nathalie N Gazaignes Sandrine S Lascaux-Cametz Anne-Sophie AS Pacanowski Jérome J Partisani Marialuisa M Launay Odile O Matheron Sophie S Rosenthal Eric E Rouveix Elisabeth E Tattevin Pierre P de Truchis Pierre P Costagliola Dominique D Goedert James J JJ

AIDS (London, England) 20130201 4

<h4>Objective</h4>To determine whether incident AIDS-defining Kaposi sarcoma or Pneumocystis jiroveci pneumonia (PJP) is associated with combination antiretroviral therapy (cART) initiation.<h4>Design</h4>Compare risk for Kaposi sarcoma and PJP by time on cART and CD4 reconstitution.<h4>Methods</h4>: In the FHDH-ANRS CO4 cohort (N = 66 369), Kaposi sarcoma (N = 1811) and PJP (N = 1718) incidence rates were computed by demographic and HIV strata. Crude and adjusted relative risk (RR) with 95% con ...[more]

PMID: 23196937

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Project description:ImportanceStudies performed in the 1980s and early 1990s have shown that people who develop Kaposi sarcoma (KS) are at higher risk of developing other cancers. The demographics of those affected with human immunodeficiency virus (HIV)/AIDS and KS have changed, and individuals with HIV/AIDS and KS now live longer.ObjectivesTo test the hypothesis that the secondary cancers developing in patients with KS have changed in recent years and to assess the risk of secondary cancers after KS in different periods.Design, setting, and participantsLongitudinal data from 9 cancer registries in the Surveillance, Epidemiology, and End Results (SEER) database were used to identify cases of KS diagnosed from January 1973 to December 2013. The dates of the analysis were November 2016 to February 2017.Main outcomes and measuresThe primary outcome was the development of secondary cancers in individuals with KS. Secondary cancers were considered only if diagnosed 2 months after a diagnosis of KS. Standardized incidence ratios (SIRs) were calculated for the development of new secondary cancers in the pre-AIDS era (1973-1979), pre-highly active antiretroviral therapy (HAART) era (1980-1995), and HAART era (1996-2013). Stratified analysis was then performed on a subset of the cases diagnosed from 1996 to 2013 based on age at diagnosis (<65 and ≥65 years), latency period between KS and the development of secondary cancers (1 year, 2-5 years, >5 to 10 years, and >10 years), and registries with higher vs lower reported rates of HIV/AIDS.ResultsAmong 14 905 individuals with diagnosed KS, 13 721 (92.1%) were younger than 65 years at the time of diagnosis, and 14 356 (96.3%) were male. From 1980 to 1995, SIRs were 2.01 (95% CI, 1.00-3.60) for cancer of the rectum, 49.70 (95% CI, 33.53-70.94) for cancer of the anus, 4.98 (95% CI, 2.79-8.22) for cancer of the liver, 13.70 (95% CI, 2.82-40.03) for cancer of the cervix, 6.40 (95% CI, 2.76-12.60) for Hodgkin lymphoma, and 48.97 (95% CI, 44.85-53.36) for non-Hodgkin lymphoma. From 1996 to 2013, cancer of the anus, Hodgkin lymphoma, non-Hodgkin lymphoma, and cancer of the liver remained associated with KS, with the addition of the following significant SIRs: 6.99 (95% CI, 3.20-13.27) for cancer of the tongue, 10.28 (95% CI, 1.24-37.13) for cancer of the penis, and 17.62 (95% CI, 3.63-51.49) for acute lymphocytic leukemia. The SIR of developing any tumor after KS decreased significantly from 3.36 to 1.94 from the pre-HAART era to the HAART era.Conclusions and relevanceThere has been a significant decline in the overall risk of secondary cancers after KS. Certain cancers, including acute lymphocytic leukemia, cancer of the tongue, and cancer of the penis, are increasingly becoming more common in the HAART era compared with the pre-HAART era. Close monitoring and screening for these secondary cancers is desirable in patients with KS.

Project description:BackgroundAIDS-related Kaposi sarcoma (AIDS-KS), a common malignancy in Kenya is associated with high morbidity and mortality. AIDS-KS is treated using bleomycin and vincristine (BV) plus or minus doxorubicin in most low resource settings, with response rates ranging from 24.8 to 87%. Survival in low resource settings has not been well documented. We report the three-year survival in a cohort of seventy patients referred to Moi Teaching and Referral Hospital (MTRH).MethodsStudy participants are part of a randomized phase IIA trial on the use of gemcitabine compared to bleomycin plus vincristine for the treatment of Kaposi sarcoma after combination antiretroviral therapy (cART) in Western Kenya. All patients were followed for three years in MTRH. Survival was determined by three monthly physical examination and analysed using Kaplan-Meier method, while possible determinants of survival such as baseline characteristics, type of chemotherapy, initial CD4 counts, age at enrolment, gender and early response to chemotherapy were analysed using univariate and multivariate Cox regression.ResultsParticipants were aged between 19 and 70?years with 56% being male. The median CD4 count was 224 cells/?l, median duration of HIV diagnosis was 12.0?months and median duration of KS lesions after histology diagnosis before initiating chemotherapy was 4.8?weeks. At three years, 60 (85.7%) patients were alive. Six of those who died were under treatment with BV while four with gemcitabine. There was no difference in the probability of survival between the patients on either treatment arm (HR?=?0.573 [95% C. I 0.143, 2.292; p?=?0.4311]). Additionally, the hazard ratio (HR) for response after six weeks, age at enrolment and gender indicated that they were not significant determinants of survival. Patients with normal CD4 cell counts (>?=?500/?l), had a HR of 0.401(0.05,3.23; p?=?0.391), suggesting better survival.ConclusionsPatients with AIDS-KS treated with combined antiretroviral drugs had excellent three-year survival regardless of whether they were treated with BV or gemcitabine as first line therapy. An initial CD4 cell count of >?=?500/?l appeared to improve survival while gender, age and early response to chemotherapy were not predictors of survival after three years.Trial registrationNumber PACTR201510001.

Project description:BACKGROUND:The optimal approach to HIV-associated Kaposi sarcoma (HIV-KS) in sub-Saharan Africa is unknown. With large-scale rollout of highly active antiretroviral therapy (HAART) in South Africa, we hypothesized that survival in HIV-KS would improve and administration of chemotherapy in addition to HAART would be feasible and improve KS-specific outcomes. METHODS:We conducted a randomized, controlled, open-label trial with intention-to-treat analysis. Treatment-naive patients from King Edward VIII Hospital, Durban, South Africa, a public-sector tertiary referral center, with HIV-KS, but no symptomatic visceral disease or fungating lesions requiring urgent chemotherapy, were randomized to HAART alone or HAART and chemotherapy (CXT). HAART arm received stavudine, lamivudine, and nevirapine (Triomune; CXT arm received Triomune plus bleomycin, doxorubicin, and vincristine every 3 weeks. When bleomycin, doxorubicin, and vincristine were not available, oral etoposide (50-100 mg for 1-21 days of a 28-day cycle) was substituted. Primary outcome was overall KS response using AIDS Clinical Trial Group criteria 12 months after HAART initiation. Secondary comparisons included time to response, progression-free survival, overall survival, adverse events, HIV control, CD4 reconstitution, adherence, and quality of life. RESULTS:Fifty-nine subjects were randomized to HAART and 53 to CXT; 12-month overall KS response was 39% in the HAART arm and 66% in the CXT arm (difference, 27%; 95% confidence interval, 9%-43%; P = 0.005). At 12 months, 77% were alive (no survival difference between arms; P = 0.49), 82% had HIV viral load <50 copies per milliliter without difference between the arms (P = 0.47); CD4 counts and quality-of-life measures improved in all patients. CONCLUSIONS:HAART with chemotherapy produced higher overall KS response over 12 months, whereas HAART alone provided similar improvement in survival and select measures of morbidity. In Africa, with high prevalence of HIV and human herpes virus-8 and limited resources, HAART alone provides important benefit in patients with HIV-KS.

Project description:PurposeIn sub-Saharan Africa, Kaposi sarcoma (KS) is the most common HIV-associated cancer. KS causes substantial morbidity, and treatment goals should emphasize quality of life (QOL). Antiretroviral therapy (ART) is indicated, and early chemotherapy significantly improves tumor regression. The effect of ART alone or with chemotherapy on QOL in treatment-naïve South Africans with HIV-associated KS was assessed.MethodsKAART (Kaposi Sarcoma AIDS Anti-Retroviral Therapy) is a randomized, controlled, open-label trial of ART versus ART plus chemotherapy. Crossover between arms was allowed for patients with progressive disease. Eighty-nine percent of patients had advanced tumor burden. Within KAART, QOL measured by European Organization for Research and Treatment of Cancer-QLQ-C30 questionnaire evaluated functional and symptom domains and global QOL. Intragroup changes between baseline and month 12 (Wilcoxon rank sign test), changes between the arms (Mann-Whitney test), and the relationship between responses, determined by AIDS Clinical Trial Group criteria and QOL measures (Kruskal-Wallis test), were evaluated. P values < .01 were considered significant.ResultsQOL information was available for 111 of 112 patients. Significant improvements over 12 months were seen in global health status and functional scales (emotional, cognitive, and social scales; not physical and role function). Most symptom scales (fatigue, pain, dyspnea, insomnia, appetite, diarrhea, and constipation) also showed significant improvement. There were no statistically significant changes between arms in intention-to-treat analysis. Patients showing a response to the tumor (complete or partial) reported significantly increased global QOL ( P < .001), pain relief, and improved role functioning. Adherence, adverse events, HIV viral load, and CD4 count did not correlate with global QOL.ConclusionAfrican patients with HIV-associated KS derive a significant benefit in QOL from ART and tumor regression.

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

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

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