AIDS-associated Kaposi's sarcoma is linked to advanced disease and high mortality in a primary care HIV programme in South Africa

Journal of the International AIDS Society AIDS-associated Kaposi's sarcoma is linked to advanced disease and high mortality in a primary care HIV programme in South Africa Kathryn M Chu 0 3 Gcina Mahlangeni 2 Sarah Swannet 2 Nathan P Ford 0 1 3 Andrew Boulle 1 Gilles Van Cutsem 1 2 0 Medecins Sans Frontieres , Braamfontein, Johannesburg , South Africa 1 Infectious Disease Epidemiology Unit, School of Public Health and Family Medicine University of Cape Town , Observatory, Cape Town , South Africa 2 Medecins Sans Frontieres , Khayelitsha, Cape Town , South Africa 3 Medecins Sans Frontieres , Braamfontein, Johannesburg , South Africa Background: AIDS-associated Kaposi's sarcoma is an important, life-threatening opportunistic infection among people living with HIV/AIDS in resource-limited settings. In western countries, the introduction of combination antiretroviral therapy (cART) and new chemotherapeutic agents has resulted in decreased incidence and improved prognosis of AIDS-associated Kaposi's sarcoma. In African cohorts, however, mortality remains high. In this study, we describe disease characteristics and risk factors for mortality in a public sector HIV programme in South Africa. Methods: We analysed data from an observational cohort study of HIV-infected adults with AIDS-associated Kaposi's sarcoma, enrolled between May 2001 and January 2007 in three primary care clinics. Paper records from primary care and tertiary hospital oncology clinics were reviewed to determine the site of Kaposi's sarcoma lesions, immune reconstitution inflammatory syndrome stage, and treatment. Baseline characteristics, cART use and survival outcomes were extracted from an electronic database maintained for routine monitoring and evaluation. Cox regression was used to model associations with mortality. Results: Of 6292 patients, 215 (3.4%) had AIDS-associated Kaposi's sarcoma. Lesions were most commonly oral (65%) and on the lower extremities (56%). One quarter of patients did not receive cART. The mortality and lost-tofollow-up rates were, respectively, 25 (95% CI 19-32) and eight (95% CI 5-13) per 100 person years for patients who received cART, and 70 (95% CI 42-117) and 119 (80-176) per 100 person years for patients who did not receive cART. Advanced T stage (adjusted HR, AHR = 5.3, p < 0.001), advanced S stage (AHR = 5.1, p = 0.008), and absence of chemotherapy (AHR = 2.4, p = 0.012) were associated with mortality. Patients with AIDS-associated Kaposi's sarcoma presented with advanced disease and high rates of mortality and loss to follow up. Risk factors for mortality included advanced Kaposi's sarcoma disease and lack of chemotherapy use. Contributing factors to the high mortality for patients with AIDS-associated Kaposi's sarcoma likely included late diagnosis of HIV disease, late accessibility to cART, and sub-optimal treatment of advanced Kaposi's sarcoma. Conclusions: These findings confirm the importance of early access to both cART and chemotherapy for patients with AIDS-associated Kaposi's sarcoma. Early diagnosis and improved treatment protocols in resource-poor settings are essential. - Background AIDS-associated Kaposis sarcoma (AIDS-KS) is an important, life-threatening opportunistic infection among people living with HIV/AIDS in resource-limited settings. Treatment with combination antiretroviral treatment (cART) has led to a sharp decline in AIDS-KS incidence and mortality in European and North American cohorts [1-6]. Combination ART has also resulted in regression of Kaposis sarcoma (KS) disease and even complete remission of KS lesions [7-9]. Adjuvant systemic chemotherapy appears to improve outcomes in advanced cases [10,11], particularly with newer chemotherapeutic agents, such as liposomal anthracyclines and taxanes, which have improved efficacy and tolerability compared with older drugs, such as bleomycin, doxorubicin, vincristine, vinblastine or adriamycin [12], However, in sub-Saharan Africa, where cART is still not widely available and chemotherapy is very limited, KS mortality remains high [12]. In this study, we describe disease characteristics and risk factors for mortality in patients with AIDS-KS in a routine HIV programme in South Africa. Study site We focused on three primary care HIV clinics in Khayelitsha, a poor township (population c.500,000) located in Cape Town, South Africa, with an adult antenatal prevalence of HIV of 33% [13]. Combination ART is provided by the provincial Department of Health with support from Mdecins Sans Frontires (MSF). All patients were started on either nevirapine- or efavirenz-based triple therapy according to provincial treatment protocols. At their initial visit, patients were examined for evidence of opportunistic infections, including AIDS-KS. Diagnoses were made clinically, and protocols recommended that those with AID-KS be started on cART irrespective of CD4 count, and those with advanced or extensive disease be referred to hospital oncology services for consideration of chemotherapy or radiotherapy. Methods Our study included HIV-infected individuals enrolled between May 2001 and January 2007. Children (<18 years) were excluded. A chart review of patients with AIDS-KS was conducted to describe stage, anatomic distribution and treatment. Initial KS stage was determined using the AIDS Clinical Trials Group staging system that classifies tumour (T), immune (I) and systemic illness (S) status into good and poor risk [14]. KS immune reconstitution inflammatory syndrome (IRIS) was defined as worsening of KS disease soon after cART initation [15]. Disseminated cutaneous lesions were defined as 25 or more external lesions or the appearance of 10 or more new lesions over one month. Chemotherapeutic agents used included bleomycin, vinblastine, vincristine, etoposide, cyclophosamide, adriamyacin and prednisone. There were no standard chemotherapeutic regimens; some patients received monotherapy, while others were treated with multiple drugs. An average of 6.5 cycles (range 1-20) was given to patients who received chemotherapy. Biopsies to confirm histology were performed only if the clinical diagnosis of KS was questionable (3%, seven patients). Baseline characteristics, cART use and survival outcomes were extracted from an electronic database maintained for routine monitoring and evaluation. Survival outcomes were defined as death, loss to follow up (LTFU), transferred, or alive and on treatment, and were censored on 31 December 2007. Patient time to LTFU and death were calculated from date of AIDS-KS diagnosis. Patients were defined as LTFU if their last clinic visit occurred more than three months prior to 31 December 2007 and were censored at their last contact date. Transfers were censored at the transfer date. The national death registry and local hospital records were used to confirm vital status. Cox proportional hazard models were built to model determinants of mortality and the Kaplan-Meier method was (...truncated)