Zimbabwean women with HIV/AIDS who present with AIDS-related Kaposi sarcoma (AIDS-KS) are younger than male counterparts of similar AIDS-KS status and have a more severe course of KS, according to the findings of a cross-sectional study published in the March 1st edition of the Journal of Acquired Immune Deficiency Syndromes.
Kaposi sarcoma was first described in 1872 by Moritz Kaposi as a disease of elderly Mediterranean or Jewish men. KS typically manifests itself as multiple purple-coloured skin lesions. When HIV/AIDS emerged in the early 1980s, KS was one of the first recognised clinical manifestations of HIV infection. Recent findings of a herpetic-like viral DNA in Kaposi's sarcoma tissue have suggested an infectious co-factor for AIDS-KS and human herpesvirus 8 is found in Kaposi's sarcoma tumors of all types.
The epidemiology of AIDS-KS appears to be complex with gender differences playing some unknown role. In North America and Europe, the risk of AIDS-KS is greater in men; this gender difference can be explained by the epidemiology of HIV-1 and KS herpesvirus (KSHV). However, in sub-Saharan Africa where the seroprevalence of HIV-1 and KSHV are similar, men still have a greater risk for AIDS-KS.
AIDS-KS is rare in women outside sub-Saharan Africa and the current published data indicate a more extensive disease and worse outcome in women. Given the paucity of data on AIDS-KS in sub-Saharan women and the lack of explanation for gender-related differences in the manifestations of AIDS-KS, a team of Zimbabwean and US researchers investigated clinical, immunologic, and virologic markers in Zimbabwean men and women with AIDS-KS.
The study took place in Parirenyatwa Hospital KS Clinic in Harare. All men and women diagnosed with AIDS-KS between 1998 and 2001 were eligible to participate. In all 438 men and 166 women with AIDS-KS participated; all were antiretroviral-naive. Participants were interviewed regarding weight loss, fever, or night seats and underwent a complete physical examination.
Laboratory investigations included liver function tests, a complete blood cell count, chest radiography, and HIV serology; CD4 counts were available for most patients. KS was confirmed by biopsy of a suspected lesion for all patients. The clinical stage of KS was established by an established staging classification. KSHV DNA in blood cells or plasma was determined by real-time polymerase-chain reaction (PCR).
In general, female patients were younger than male patients (median and range of 33 (19-73) versus 38 (17-73); p
Systemic symptoms included fever, diaphoresis, or weight loss. A multivariate model which adjusted for age and CD4 counts revealed no significant gender-related differences in all the measured parameters except that women were more likely than men to have systemic symptoms (OR =1.8, 95 % CI 1.2-2.7; p = 0.008).
A multivariate model which adjusted for the effect of prior treatment also provided a similar conclusion (OR =1.7, 95 % CI 1.1-2.7; p = 0.009). Univariate analysis confirmed that the frequency of systemic symptoms were significantly higher in females by comparison with males (52 % versus 38 %; p = 0.001). Overall, there were no statistically significant gender-related differences in AIDS-KS stages, prior or current chemotherapy or radiation, CD4 counts, plasma or cellular KSHV DNA load, nor the frequency of KSHV DNA detectable by PCR.
The study by Amie Meditz and Thomas Campbell of the University of Colorado is the first systematic description of AIDS-KS in African women and the first comparison of viral and immunologic markers between men and women, and the first to demonstrate that there might be gender-related differences in the biology and pathogenesis of AIDS-KS since women are at a significantly higher risk of systemic symptoms than men.
The authors speculate that other co-infections in women, which were not considered in the study, might have contributed to the gender-related differences in disease severity. For example, the increased proinflammatory cytokines associated with such infections might have contributed to the AIDS-KS pathogenesis. However, the authors did not specify the gender-specific co-infections that might have been responsible.
The policy implication of the study is that health care workers should pay more attention to women with AIDS-KS since they bear the brunt of the morbidity. The authors call for additional studies designed to unravel the mechanisms which result in the differential susceptibility of women to the ravages of AIDS-KS. The authors specifically cite parity, menstrual status, and female sex hormones as gender-specific factors which could be investigated further.
A landmark discovery by Kaleeba and Berger recently identified the receptor by which KSHV infects human cells and which might play a crucial role in the development of KS. It would be informative to establish whether there are gender-related differences in the expression of this receptor.
These and other studies might provide the vital information which will inform on the development of novel interventions for women with AIDS-KS.
Meditz AL et al. Gender differences in AIDS-associated Kaposi sarcoma in Harare, Zimbabwe. J Acquir Immune Defic Syndr 44: 306-308, 2007.
Kaleeba JAR and Berger EA. Kaposi’s sarcoma-associated herpesvirus fusion-entry receptor: cystine transporter xCT. Science 311: 1921-1924, 2006.