KS in Africa: people with low CD4 counts still at risk despite ART

The incidence of Kaposi’s Sarcoma (KS) among HIV-infected adults on ART in Uganda and Kenya remains high (346 per 100,000 person-years) until the CD4 cell count rises above 350 cells/mm³, highlighting the importance of starting ART early, researchers from the East Africa IeDEA epidemiological collaborative group reported at the 19^th Conference on Retroviruses and Opportunistic Infections in Seattle last week.

This ongoing high incidence of Kaposi’s sarcoma, the most commonly reported AIDS-defining cancer in sub-Saharan Africa, compares with an incidence of 150 cases per 100,000 person-years for prostate cancer, the most common cancer in the United States. Kaposi's sarcoma, a cancer which develops from blood vessels in the skin and some internal organs, very predominantly affects men who have sex with men in the developed world, but is a widespread AIDS-defining condition in sub-Saharan Africa due to the high prevelance of the causative virus (HHV-8) in the population, especially in eastern Africa.

In this three-year prospective cohort evaluation of over 98,000 adults in 26 different routine HIV care sites Jeffrey Martin noted that antiretroviral treatment was associated with a 55% - 90% reduction in the incidence of KS incidence, with the most pronounced reduction in individuals with CD4 cell counts above 350 cells/mm³.

In resource-rich settings an established epidemiological infrastructure was able to quickly document a significant decrease in KS incidence (approximately 60 to 90%) after the introduction of HAART in the mid-1990s.

The same cannot be said of resource-poor settings where such an infrastructure is largely absent, so limiting the understanding of the effect of ART on KS.

East Africa IeDEA has addressed this gap and follows approximately 120,000 HIV-infected adults and 15,000 children in routine care at 40 HIV care clinics in Uganda, Kenya and Tanzania.

The researchers chose to look at the change in the overall burden of KS incidence; the impact of ART on KS incidence; and what future KS incidence might be with the ‘successful’ use of ART, that is when CD4 cell counts are 350 cells/mm³ or above.

HIV-infected adults without KS in clinics in Mbarara, Uganda, and in western Kenya were followed from October 2008 and included existing patients or those who joined the clinic after October 2008. Patients were followed until they developed KS, died, were lost to follow-up or reached the end of the study in August 2011. Once a patient started ART they were considered to be on ART regardless of adherence and/or interruptions.

KS was diagnosed through use of a punch biopsy to enhance the sensitivity/specificity of KS diagnosis in addition to standard clinical-only diagnosis. (Around 20 - 25% of clinical diagnoses were subsequently determined to be conditions other than KS).

Incident KS was defined as a new case of KS 30 days after clinic enrolment. A clinical diagnosis was accepted in the absence of a biopsy.

Just over 98,000 adults were enrolled in the study at baseline, having a median age of 35 years. The majority were female (approximately 70%), and most (87,430) were from Kenya. At the time of entry into the cohort 37% were on ART and the median CD4 cell count was 277 cells/mm³. Patients were followed for a total of 144,812 person years with a median of 1.8 years (IQR: 0.5 to 2.6 years) with 72% having received ART (almost exclusively NNRTI-based) during this time.

Rates of KS incidence were similar in both countries. A total of 499 cases were diagnosed, of which 53% and 45% were confirmed by biopsy in Uganda and Kenya respectively, with an overall incidence of 346 per 100,000 person-years.

Nevertheless overall incidence for the past three years has remained more or less the same in all routine care clinics, even though the number enrolled on ART has grown.

However KS incidence has declined significantly in patients receiving ART; after adjusting for age and sex, incidence showed an overall decline of 55% (HR: 0.45 95% CI: 0.37-0.53). A further adjustment by CD4 cell count, even though this is time-dependent, showed that the risk of KS doubled in those with CD4 cell counts between 200 and 350 when compared with those with CD4 counts above 350. The risk was threefold higher in those with CD4 counts between 100-200, six times higher in the 50-100 range and 15-fold higher in those with CD4 counts below 50.

Dr. Martin noted such a large sample size from a real-life setting is essentially observational and does not allow for more precise findings as a research protocol would. It is probable that cases diagnosed as incident KS on ART may have started before going on ART. This will lead to an overestimation of KS incidence on ART.

Dr. Martin concluded even with the increased availability of ART in resource-poor settings KS is still evident at the population level with a high burden of incident KS at HIV care clinics.

In spite of the relative benefits of ART compared to no ART in reducing incident KS, it is only when CD4 cell counts are at 350 cells/mm³ or above that ART has a significant impact on the incidence of this AIDS-defining malignancy, highlighting the need for the earlier start of ART.