Abstract
BackgroundKaposi sarcoma (KS) is the most common AIDS-defining tumour in HIV-infected individuals in Africa. Kaposi sarcoma herpes virus (KSHV) infection precedes development of KS. KSHV co-infection may be associated with worse outcomes in HIV disease and elevated KSHV viral load may be an early marker for advanced HIV disease among untreated patients. We examined the prevalence of KSHV among adults initiating antiretroviral therapy (ART) and compared immunological, demographic and clinical factors between patients seropositive and seronegative for KSHV.ResultsWe analyzed cross-sectional data collected from 404 HIV-infected treatment-naïve adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa between November 2008 and March 2009. Subjects were screened at ART initiation for antibodies to KSHV lytic K8.1 and latent Orf73 antigens. Seropositivity to KSHV was defined as positive to either lytic KSHV K8.1 or latent KSHV Orf73 antibodies. KSHV viremia was determined by quantitative PCR and CD3, 4 and 8 lymphocyte counts were determined with flow cytometry. Of the 404 participants, 193 (48%) tested positive for KSHV at ART initiation; with 76 (39%) reactive to lytic K8.1, 35 (18%) to latent Orf73 and 82 (42%) to both. One individual presented with clinical KS at ART initiation. The KSHV infected group was similar to those without KSHV in terms of age, race, gender, ethnicity, smoking and alcohol use. KSHV infected individuals presented with slightly higher median CD3 (817 vs. 726 cells/mm3) and CD4 (90 vs. 80 cells/mm3) counts than KSHV negative subjects. We found no associations between KSHV seropositivity and body mass index, tuberculosis status, WHO stage, HIV RNA levels, full blood count or liver function tests at initiation. Those with detectable KSHV viremia (n = 19), however, appeared to present with signs of more advanced HIV disease including anemia and WHO stage 3 or 4 defining conditions compared to those in whom the virus was undetectable.ConclusionsWe demonstrate a high prevalence of KSHV among HIV-infected adults initiating ART in a large urban public-sector HIV clinic. KSHV viremia but not KSHV seropositivity may be associated with markers of advanced HIV disease.
Highlights
Kaposi sarcoma (KS) is the most common AIDS-defining tumour in HIV-infected individuals in Africa
While Kaposi sarcoma herpes virus (KSHV)-specific CD8+ T cell epitope responses have been shown to increase after initiation of HAART [27,28], it has yet to be determined if T-lymphocyte subpopulations are a marker of advanced disease stage in antiretroviral therapy (ART) naive patients infected with KSHV and if this has implications for treatment initiation guidelines
We demonstrated a high prevalence of KSHV in this population and found that few factors associated with advanced HIV disease stage and progression were associated with KSHV seropositivity
Summary
Kaposi sarcoma (KS) is the most common AIDS-defining tumour in HIV-infected individuals in Africa. Several clinical and laboratory markers have been associated with advanced disease stage among untreated HIV-infected individuals [13,14,15,16,17,18,19,20,21], including the T-lymphocyte subpopulations, CD4+ and CD8+ [14,18,22,23,24,25,26] which play an important role in the response to viral infections. We enrolled subjects in a cohort study to determine the impact of KSHV on response to HAART as well as the effects of HAART on KSHV control This cross-sectional analysis forms part of this larger study and aimed to measure the prevalence of KSHV infection among these HIV-infected adults initiating ART in a large treatment programme in Johannesburg, South Africa and to compare T-lymphocyte subpopulations and other demographic, clinical and laboratory factors between patients seropositive and seronegative for KSHV at enrolment
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