A Randomized Controlled Trial of Highly Active Antiretroviral Therapy Versus Highly Active Antiretroviral Therapy and Chemotherapy in Therapy-Naive Patients With HIV-Associated Kaposi Sarcoma in South Africa

Abstract

Background The optimal approach to HIV-associated KS (HIV-KS) in sub-Saharan Africa is unknown. With large-scale rollout of highly active antiretroviral therapy (HAART) in South Africa, we hypothesized 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-naïve 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 (ABV) every 3 weeks. When ABV was not available, oral etoposide (50-100 mg days 1-21 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 59 subjects were randomized to HAART, 53 to CXT. 12-month overall KS response was 39% in the HAART arm and 66% in the CXT arm (difference 27%; 95% CI 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/mL without difference between arms, (p=0.47); CD4 counts and QOL measures improved in all patients. Conclusions HAART with chemotherapy produced higher overall KS response over 12 months, while HAART alone provided similar improvement in survival and select measures of morbidity. In Africa, with high prevalence of HIV and HHV-8 and limited resources, HAART alone provides important benefit in patients with HIV-KS.

Laryngeal Kaposi's Sarcoma Complicated by the Immune Reconstitution Inflammatory Syndrome in an HIV-infected Patient

“…It was reported that 6.6% of KS patients developed IRIS (4). Furthermore, previous studies demonstrated that KS-IRIS can be serious or even fatal (5). We herein report a case of laryngeal KS that was complicated by IRIS and treated successfully with pegylated liposomal doxorubicin (PLD).…”

Kaposi’s Sarcoma Epidemiology, Risk Factors, Staging and Treatment: AN OVERVIEW.

“…There are two small randomized trials that have looked at the role of chemotherapy plus ART and ART alone. The overall response rate of the KS was significantly better for patient in chemotherapy plus the ART group, but there was no overall survival difference between the groups [74,75]. Also we know that HHV-8 is an etiologic agent of virally associated tumors such as Kaposi sarcoma.…”

Suspected metastatic Adrenocortical Carcinoma revealing as Pulmonary Kaposi Sarcoma in Adrenal Cushing's syndrome

“…The therapy varies according to the type of KS. In the case of epidemic (HIV-related) or iatrogenic KS, treatment primarily aims at immune reconstitution by means of highly active antiretroviral therapy (HAART) or reduction of immunosuppressive therapy, respectively [11,12].…”