Browsing by Author "Uldrick, Thomas S."

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A randomized controlled trial of HAART versus HAART and chemotherapy in therapy-naïve patients with HIV-associated Kaposi sarcoma in South Africa.
(Lippincott Williams & Wilkins., 2011) Mosam, Anisa.; Shaik, Fahmida.; Uldrick, Thomas S.; Esterhuizen, Tonya.; Friedland, Gerald H.; Scadden, David T.; Aboobaker, Jamila B.; Coovadia, Hoosen Mahomed.
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.
Seroprevalence and viral quantification of Kaposi Sarcoma-associated Herpes Virus (KSHV) in a Human Immunodeficiency Virus (HIV) infected adult South African cohort.
(2017) Singh, Shoohana.; Mosam, Anisa.; Shaik, Fahmida.; Uldrick, Thomas S.; Naidoo, Kogieleum.
Background Kaposi sarcoma-associated herpes virus (KSHV), also known as human herpes virus 8 (HHV8), is aetiologically implicated in Kaposi’s sarcoma (KS). Although HIV associated KS has increased in incidence and is a public health problem in South Africa, serological studies of KSHV have not been extensively documented in this population. This cross-sectional study investigates the seroprevalence and viral load of KSHV in an adult South African cohort. Method Cross-sectional data of 140 participants attending an urban research HIV counseling and testing (HCT) clinic site in Durban, KwaZulu-Natal, between July and October 2013 was analyzed. Detection of antibodies against latent (Orf73) and lytic (K8.1) KSHV antigens was performed on 70 HIV-seropositive and 70 HIV-seronegative participants. Subjects reactive to either antigen were considered KSHV seropositive and analyzed for salivary KSHV DNA, which was quantified using primers for the K6 gene region. Results The demographic characteristics of the two groups were similar, with 36% males (median age, 35yrs.) and 64% females (med. age, 34yrs.) in the HIV-positive group, and 31% males (med. age, 36.5yrs.) and 69% females (med. age, 36.5yrs.) in the HIV-negative group. Of 70 HIV-positive participants, 100% were black Africans, as was 97% of the HIV-negative group, with the remaining 3% being Indian/Asian and Mixed race. Only 24% of HIV-positive patients were on Anti-retro viral treatment. Fifty-four percent of all participants tested positive for KSHV, with 33% reactive to lytic K8.1, 37% to latent Orf73 and 21% to both. Of those HIV-positive, 50% were seropositive for K8.1 and 46% for Orf73. In those HIV-negative, 16% were seropositive for K8.1 and 29% for Orf73. The HIV-positive group demonstrated a significantly higher percentage KSHV seropositivity (70% vs. 37%, p=0.0001). Amongst the KSHV seropositive participants, KSHV DNA was detected in 41 % HIV-positive and 23% HIV-negative participants. Conclusion KSHV seroprevalence was high in South African adults attending an urban HCT clinic. HIV positive status was associated with a higher KSHV seropositivity and a greater KSHV salivary shedding. HIV positive individuals should be tested for KSHV infection and those found infected, be monitored aggressively for development of KS.