Kaposi sarcoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy.
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ABSTRACT:
SUBMITTER: Franceschi S
PROVIDER: S-EPMC2528138 | biostudies-other | 2008 Sep
REPOSITORIES: biostudies-other
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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.
| S-EPMC3360837 | biostudies-literature
Project description:Although ultraviolet radiation (UVR) is established as both an inducer of herpes simplex virus reactivation and as the primary risk factor for many common skin cancers, its relationship with human herpes virus 8 (HHV8) infection or risk of Kaposi sarcoma (KS) is unknown. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between ambient UVR, history of nonmelanoma skin cancer (NMSC; as a biomarker of personal cumulative UVR dose), and incidence of first primary KS in a nationwide US cohort of white and African American male veterans infected with HIV between 1986 and 1996 (prior to the widespread availability of treatment) using Cox regression. All statistical tests were two-sided. Based on discharge records, there were 422 newly diagnosed KS cases among 17 597 HIV-infected veterans. Cohort members with prior NMSC had a statistically significantly increased risk of KS (HR = 8.64, 95% CI = 6.23 to 11.96) in the total population. Risk of KS was higher for quartile 4 vs 1 among the total population (HR = 1.49, 95% CI = 1.02 to 2.16, Ptrend UVR quartile [coded 1 to 4] = .02) and among whites (HR = 1.75, 95% CI = 1.11 to 2.78, Ptrend = .009), but not among African Americans (HR = 1.23, 95% CI = 0.71 to 2.15, Ptrend = .23). KS risk was elevated among HIV-infected men with NMSC diagnosis and in those living in locations with high ambient UVR at time of HIV diagnosis. Our novel findings suggesting that UVR exposure may increase KS risk warrant further investigation.
| S-EPMC6059100 | biostudies-literature
Project description:BACKGROUND:The risk of Kaposi sarcoma (KS) among HIV-infected persons on antiretroviral therapy (ART) is not well defined in resource-limited settings. We studied KS incidence rates and associated risk factors in children and adults on ART in Southern Africa. METHODS:We included patient data of 6 ART programs in Botswana, South Africa, Zambia, and Zimbabwe. We estimated KS incidence rates in patients on ART measuring time from 30 days after ART initiation to KS diagnosis, last follow-up visit, or death. We assessed risk factors (age, sex, calendar year, WHO stage, tuberculosis, and CD4 counts) using Cox models. FINDINGS:We analyzed data from 173,245 patients (61% female, 8% children aged <16 years) who started ART between 2004 and 2010. Five hundred and sixty-four incident cases were diagnosed during 343,927 person-years (pys). The overall KS incidence rate was 164/100,000 pys [95% confidence interval (CI): 151 to 178]. The incidence rate was highest 30-90 days after ART initiation (413/100,000 pys; 95% CI: 342 to 497) and declined thereafter [86/100,000 pys (95% CI: 71 to 105), >2 years after ART initiation]. Male sex [adjusted hazard ratio (HR): 1.34; 95% CI: 1.12 to 1.61], low current CD4 counts (?500 versus <50 cells/?L, adjusted HR: 0.36; 95% CI: 0.23 to 0.55), and age (5-9 years versus 30-39 years, adjusted HR: 0.20; 95% CI: 0.05 to 0.79) were relevant risk factors for developing KS. INTERPRETATION:Despite ART, KS risk in HIV-infected persons in Southern Africa remains high. Early HIV testing and maintaining high CD4 counts is needed to further reduce KS-related morbidity and mortality.
| S-EPMC4231535 | biostudies-literature
Project description:Background Kaposi sarcoma (KS) remains a frequent cancer in human immunodeficiency virus (HIV)-positive patients starting combination antiretroviral therapy (cART). We examined incidence rates and risk factors for developing KS in different periods after starting cART in patients from European observational HIV cohorts.Methods We included HIV-positive adults starting cART after 1 January 1996. We analyzed incidence rates and risk factors for developing KS up to 90 and 180 days and 1, 2, 5, and 8 years after cART start and fitted univariable and multivariable Cox regression models.Results We included 109 461 patients from 21 prospective clinical cohorts in Europe with 916 incident KS cases. The incidence rate per 100 000 person-years was highest 6 months after starting cART, at 953 (95% confidence interval, 866-1048), declining to 82 (68-100) after 5-8 years. In multivariable analyses adjusted for exposure group, origin, age, type of first-line regimen, and calendar year, low current CD4 cell counts increased the risk of developing KS throughout all observation periods after cART initiation. Lack of viral control was not associated with the hazard of developing KS in the first year after cART initiation, but was over time since starting cART increasingly positively associated (P < .001 for interaction).Conclusion In patients initiating cART, both incidence and risk factors for KS change with time since starting cART. Whereas soon after starting cART low CD4 cell count is the dominant risk factor, detectable HIV-1 RNA viral load becomes an increasingly important risk factor in patients who started cART several years earlier, independently of immunodeficiency.
| S-EPMC5091347 | biostudies-literature
Project description:BackgroundProtease inhibitors (PIs) may inhibit Kaposi sarcoma (KS) carcinogenesis. However, PI-based antiretroviral therapy (ART) is rarely a first-line choice in people living with HIV (PLWH) because of cost and toxicities. This is the first systematic review to assess KS incidence stratified by ART type.MethodsWe searched PubMed to identify original, full research reports of KS incidence in ART-treated adult PLWH, stratified by ART class, published between 1996 and 2017. For overlapping cohorts, we included only the most recent study and supplemented data with earlier relevant analyses. We described study design, sociodemographic characteristics, statistical adjustment factors, and KS incidence.ResultsWe identified 3 unique retrospective cohort studies, and supplemented one of the studies with results from 6 previous subgroup reports, which included 242,309 PLWH and 3570 incident KS cases. Overall, KS crude incidence decreased by a factor of 10 between untreated and ART-treated PLWH; CD4-adjusted KS incidence decreased by ∼50%, with either non-nucleoside reverse transcriptase inhibitor- or PI-based ART. A single study measured a cumulative dose-/time-dependent effect of ART, which reported a relative risk reduction in only the cohort receiving boosted PI-based ART. Other studies defined ART categories by first-line therapy only.ConclusionsThe risk of incident KS was significantly reduced, regardless of ART class even after adjusting for CD4 count. The quality of evidence (ie, most studies categorizing users by first-line ART) does not permit KS risk reduction comparisons across ART types. Given the limited number and retrospective nature of these studies, prospective data are indicated.
| S-EPMC9415696 | biostudies-literature
Project description:BackgroundThe introduction of combination antiretroviral therapy (cART) has led to a significant reduction in Kaposi sarcoma (KS) incidence among people with HIV (PWH). However, it is unclear if incidence has declined similarly across key demographic and HIV transmission groups and the annual number of incident and prevalent KS cases remains unquantified.MethodsUsing population-based registry linkage data, we evaluated temporal trends in KS incidence using adjusted Poisson regression. Incidence and prevalence estimates were applied to CDC HIV surveillance data, to obtain the number of incident (2008-2015) and prevalent (2015) cases in the United States.ResultsAmong PWH, KS rates were elevated 521-fold [95% confidence intervals (CI), 498-536] compared with the general population and declined from 109 per 100,000 person-years in 2000 to 47 per 100,000 person-years in 2015, at an annual percentage change of -6%. Rates declined substantially (P trend < 0.005) across all demographic and HIV transmission groups. Of the 5,306 new cases estimated between 2008 and 2015, 89% occurred among men who have sex with men. At the end of 2015, 1,904 PWH (0.20%) had been diagnosed with KS in the previous 5 years.ConclusionsA consistent gradual decline in KS incidence has occurred among PWH in the United States during the current cART era. This decrease is uniform across key demographic and HIV transmission groups, though rates remain elevated relative to the general population.ImpactContinued efforts to control HIV through early cART initiation and retention in care need to be maintained and possibly expanded to sustain declines.
| S-EPMC8419027 | biostudies-literature
Project description:Human immunodeficiency virus (HIV) infection with advanced immunosuppression predisposes to cryptococcal meningitis (CM). We describe the incidence, clinical presentation, and outcome of CM in HIV-infected individuals during the highly active antiretroviral therapy (HAART) era.A nationwide, population-based cohort of HIV-infected individuals was used to estimate incidence and mortality of CM including risk factors. A description of neurological symptoms of CM at presentation and follow-up in the study period 1995-2014 was included in this study.Among 6,351 HIV-infected individuals, 40 were diagnosed with CM. The incidence rates were 3.7, 1.8, and 0.3 per 1000 person-years at risk in 1995-1996, 1997-1999, and 2000-2014, respectively. Initiation of HAART was associated with decreased risk of acquiring CM [incidence rate ratio (IRR), 0.1 (95% CI, 0.05-0.22)]. African origin was associated with increased risk of CM [IRR, 2.05 (95% CI, 1.00-4.20)]. The main signs and symptoms at presentation were headache, cognitive deficits, fever, neck stiffness, nausea, and vomiting. All individuals diagnosed with CM had a CD4+ cell count <200 cells/µl [median 26; interquartile range (IQR), 10-50)]. Overall, mortality following CM was high and mortality in the first 4 months has not changed substantially over time. However, individuals who survived generally had a favorable prognosis, with 86% (18/21) returning to the pre-CM level of activity.The incidence of HIV-associated CM has decreased substantially after the introduction of HAART. To further decrease CM incidence and associated mortality, early HIV diagnosis and HAART initiation seems crucial.
| S-EPMC5531720 | biostudies-other
Project description:: The search for the etiologic agent for Kaposi sarcoma led to the discovery of Kaposi sarcoma-associated herpesvirus (KSHV) in 1994. KSHV, also called human herpesvirus-8, has since been shown to be the etiologic agent for several other tumors and diseases, including primary effusion lymphoma (PEL), an extracavitary variant of PEL, KSHV-associated diffuse large B-cell lymphoma, a form of multicentric Castleman disease, and KSHV inflammatory cytokine syndrome. KSHV encodes several genes that interfere with innate and specific immunity, thwart apoptosis, enhance cell proliferation and cytokine production, and promote angiogenesis, and these play important roles in disease pathogenesis. HIV is an important cofactor in Kaposi sarcoma pathogenesis, and widespread use of antiretroviral therapy has reduced Kaposi sarcoma incidence. However, Kaposi sarcoma remains the second most frequent tumor arising in HIV-infected patients in the United States and is particularly common in sub-Saharan Africa. KSHV prevalence varies substantially in different populations. KSHV is secreted in saliva, and public health measures to reduce its spread may help reduce the incidence of KSHV-associated diseases. Although there have been advances in the treatment of Kaposi sarcoma, KSHV-multicentric Castleman disease, and PEL, improved therapies are needed, especially those that are appropriate for Kaposi sarcoma in resource-poor regions.
| S-EPMC6310482 | biostudies-literature
Project description:IntroductionThe expansion of antiretroviral therapy (ART) eligibility could lead to earlier initiation of Human Immunodeficiency Virus (HIV) treatment and consequently reduce the risk of HIV-associated Kaposi Sarcoma (KS). We investigated the impact of changes in the Nigerian HIV treatment guidelines on KS incidence among adults enrolled in HIV care in Nigeria.MethodsWe analyzed data of adults who enrolled for HIV care from January 2006 to December 2016 at one of Nigeria's largest HIV treatment centers. Based on changes in HIV treatment guidelines, we classified 2006-2009 as the pre-expansion period and 2010-2016 as the post-expansion period. We used Kaplan Meier curves to compare the incidence of KS in the pre-expansion to the post-expansion period. We used Cox regression models to assess the hazard for incident KS between the two periods after adjusting for potential confounders.ResultsAmong 14,479 patients with HIV, the overall KS incidence was 2.35; 95% CI 2.01-2.74/1,000 person-years. The incidence of KS decreased from 2.53 to 1.58 per 1,000 person-years from 2006 to 2009 to 2010-2016. In models adjusting for age, sex, CD4-T cell count, and ART use, the risk for KS remained lower in 2010-2016 compared to 2006-2009. In analyses restricted to time on ART, there was no significant difference in KS incidence between HIV patients who enrolled in 2006-2009 and 2010-2016 after adjusting for age, sex, and CD4 T-cell count.ConclusionThe expansion of ART eligibility was associated with a reduced incidence of HIV-associated KS among adults initiating HIV care in Jos, Nigeria. The reduction was likely driven by earlier enrollment for HIV care and ART initiation.
| S-EPMC10512500 | biostudies-literature
Project description:Although the independent effects of smoking status and HAART are reported as lower risks against KS, their combined effects have not been explored. We examined whether there is an interaction between smoking status and HAART use on the risk of KS development in an on-going US cohort of HIV-infected men.Cox proportional hazards regression was used to analyse a total sample of 2736 participants of the Multicenter AIDS Cohort Study (MACS).We identified 530 incident KS cases with a total follow-up time of 26?594 person-years (incidence rate: 2.00 out of 100 person-years). Current smoking status and HAART use were independently associated with a lower risk of KS development (hazard ratio - HR=0.56, 95% CI: 0.35-0.90, P=0.02 and HR=0.27, 95% CI: 0.16-0.48, P<0.0001, respectively). There was no evidence of multiplicative interaction between current smoking status and HAART use on KS risk (HR=2.14, 95% CI: 0.97-4.73, Pinteraction=0.06). Lower effect of smoking was only present among those not on HAART (HR=0.57, 95% CI: 0.35-0.92, P=0.02).The inverse association of cigarette smoking on KS risk may be limited to those not on HAART. The biological mechanism of smoking in KS carcinogenesis should be elucidated.
| S-EPMC3619085 | biostudies-other