CROI: Remission of Kaposi's sarcoma seen in rural Uganda when HIV treatment given

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A non-nucleoside reverse transcriptase inhibitor-based antiretroviral regimen appears to have a similar impact on Kaposi’s sarcoma (KS) in Ugandans to regimens based on protease inhibitors in North America and Europe, according to findings released last month. Nevertheless nearly a third of people diagnosed with KS subsequently died, despite receiving antiretroviral therapy (ART).

Researchers from Uganda and the US Centers for Disease Control presented data on the clinical outcomes for patients with AIDS-related Kaposi’s sarcoma (KS) on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART in a resource-limited setting at the Fourteenth Conference on Retroviruses and Opportunistic Infections in Los Angeles, USA.

KS is the most common AIDS-related malignancy which is associated with mortality. After the introduction of protease inhibitor-based antiretroviral therapy in North America and Europe in the mid-1990s, doctors noted that Kaposi’s sarcoma lesions often spontaneously shrank and disappeared in HIV-positive patients, and mortality associated with the condition declined substantially. There was speculation that protease inhibitors had a direct effect on Kaposi’s sarcoma independent of their effect on the immune system, although a French study published in 2006 found no difference in the rate of KS remission between patients treated with PIs or NNRTIs.

Glossary

Kaposi's sarcoma (KS)

Lesions on the skin and/or internal organs caused by abnormal growth of blood vessels.  In people living with HIV, Kaposi’s sarcoma is an AIDS-defining cancer.

chemotherapy

The use of drugs to treat an illness, especially cancer.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

However, there is a paucity of information about the clinical outcomes for AIDS-related KS in resource-poor settings where NNRTI-based ART is predominantly used. This was the background for the present study in rural Uganda.

The study evaluated HIV-infected patients aged 18 years and over who initiated ART in the Home-Based AIDS Care Project in Tororo, Uganda from May 2003 to December 2005 and were diagnosed with KS at baseline or in follow-up. The primary ART regimen was 3TC (lamivudine, Epivir), d4T (stavudine, Zerit), and nevirapine (Viramune). KS was diagnosed based on clinical grounds supported, whenever possible, by biopsies, chest X-rays, and ultrasonography.

Individuals who had KS at baseline (prevalent KS) were compared with those who developed KS during follow up (incident KS). Logistic regression was used to examine the effect of independent risk factors on prevalent or incident KS. Cox proportional hazards modeling was used to examine associations between baseline variables and risk factors for death among KS patients.

Out of the 1,125 individuals, 16 were diagnosed with prevalent KS and 17 with incident KS at baseline and during 1983 person years of follow up, respectively. A total of twelve patients received chemotherapy for their KS (three baseline and nine follow-up cases).

The median time from initiation of ART to KS diagnosis was 115 days (IQR 60-300) for incident KS, resulting in an incidence of 0.86/100 person years. Prevalent KS was distinct from incident KS by the sex distribution (31.3 % female versus 64.7 %, p = 0.02) and baseline log viral load (5.3 vs 5.9, p = 0.02). Both forms of KS were comparable for baseline CD4 cell count, body mass index, or crude mortality.

KS was associated with being male (adjusted odds ratio, AOR, 2.47, 95 % CI 1.23-5.01) and baseline CD4 cell count

Mortality was associated with visceral KS (adjusted hazard ratio, AHR, 21.5, 95 % CI 2.71-171.0) but not with baseline CD4 count or viral load and use of chemotherapy.

In conclusion, KS diagnosis at baseline or follow-up during NNRTI-based ART was associated with a high mortality rate of 30 % in a rural population in Eastern Uganda. The authors point out that KS regression rates were similar to those reported for protease-inhibitor -based ART.

References

Asiimwe F et al. Clinical outcomes of HIV-infected patients with Kaposi’s sarcoma receiving antiretroviral therapy in rural Uganda. Fourteenth Conference on Retroviruses and Opportunistic Infections, Los Angeles, abstract 880, 2007.