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A Randomized Comparison of Protease Inhibitor-based Versus Non-nucleoside Reverse Transcriptase Inhibitor-based Antiretroviral Therapy for Initial Treatment of Individuals With AIDS-related Kaposi's Sarcoma in Sub-Saharan Africa

Phase 4
18 Years
Open (Enrolling)
Kaposi's Sarcoma, HIV Infections

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Trial Information

A Randomized Comparison of Protease Inhibitor-based Versus Non-nucleoside Reverse Transcriptase Inhibitor-based Antiretroviral Therapy for Initial Treatment of Individuals With AIDS-related Kaposi's Sarcoma in Sub-Saharan Africa

With the advent of the HIV epidemic, Kaposi's sarcoma (KS) is now the most common adult
cancer in many parts of sub-Saharan Africa. In HIV-infected patients with KS in developed
settings, the initiation of highly active anti-retroviral therapy (HAART) has been
associated with regression of the tumor, in many but not all cases, even in the absence of
conventional chemotherapy. However, it is not known which specific antiretroviral drugs or
regimens are critical to convey HAART's anti-KS effect. In particular, it is not known
whether the anti-KS effects of protease inhibitors (PI) in vitro and in animal models
translate into improved clinical outcomes as compared to non-PI-based HAART regimens. To
address this, we will determine whether a PI-based HAART regimen (lopinavir/ritonavir plus
emtricitabine/tenofovir) is superior to a non-nucleoside reverse transcriptase inhibitor
(NNRTI)-based HAART regimen (efavirenz plus emtricitabine/tenofovir) in promoting the
regression of KS tumor burden in persons with AIDS-related KS in sub-Saharan Africa. We will
enroll 224 patients with AIDS-related KS in Kampala, Uganda, randomly assign them to either
a PI-based HAART or an NNRTI-based HAART regimen, and observe them for one year to determine
the response in their KS to therapy.

Inclusion Criteria:

- Age 18 years or older

- HIV-1 infection

- No prior antiretroviral therapy of any duration, including prior use to prevent
perinatal transmission within prior six months.

- No prior chemotherapy or radiotherapy for KS

- Presence of Kaposi's sarcoma, documented by biopsy by the Pathology Department at
Mulago Hospital, with at least one mucocutaneous lesion (including oral or genital
mucosal lesions), each at least 0.6 x 0.6 cm in perpendicular diameters.

- Laboratory values obtained within 21 days prior to randomization: absolute neutrophil
count equal to or more than 1000/mm3; hemoglobin > 9.0 g/dL; platelet count >
50,000/mm3; creatinine < 2 times upper limit of normal (ULN); aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) < 5 times ULN; and alkaline
phosphatase and total bilirubin < 2 times ULN.

- In women, negative urine pregnancy test within 28 days of randomization and just
before randomization.

- If a woman of child-bearing potential (i.e., not yet reached menopause or undergone
hysterectomy, bilateral oophorectomy, or tubal ligation), must be willing to use at
least two of the following methods of contraception, to be provided by the study:
condoms (male or female), IUD, or hormone-based therapy, e.g., contraceptive pills,
Norplant or Depo-Provera.

- Candidate currently resides within Uganda and does not intend to relocate away from
current geographical area of residence for the duration of study participation.

- Karnofsky performance score of 70 or more

Exclusion Criteria:

- Extensive degree of mucocutaneous KS, which would typically require chemotherapy or
radiotherapy. This is defined by any of the following:

- One or more bulky cutaneous lesions, defined as at least 5.0 cm in greatest
diameter across the surface of the skin and at least 3 cm in height

- One or more mucocutaneous lesions exhibiting ulceration

- One or more oral lesions that interfere with swallowing

- Suggestion of pulmonary or gastrointestinal visceral KS, as evidenced by any of the

- Abnormal chest x-ray within 21 days prior to randomization which is otherwise
unexplained, unless the x-ray is unchanged compared with at least 60 days

- Positive occult blood stool testing within 21 days prior to randomization or
history of overt bleeding from the mouth or rectum in the 21 days prior to

- Facial lymphedema or lymphedema in any other body region which causes symptoms (e.g.,
pain) or functional disability (e.g., any less than 85% active range of motion in a
large joint)

- Evidence of currently active, untreated opportunistic infection or malignancy (not
including Kaposi's sarcoma); or unexplained temperature which is > 38.5 degrees C

- Use of drugs, within the prior 28 days, contraindicated while taking
lopinavir/ritonavir or efavirenz because of effects on the cytochrome P450 system.
These include propafenone, astemizole, terfenadine, rifampin, rifapentine, ergot
derivatives, cisapride, lovastatin, simvastatin, pimozide, midazolam, and triazolam.

- Active drug or alcohol use that, in the investigators' opinion, would interfere with
study participation

- Breastfeeding

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Blinded assessment of the change in the burden of KS lesions

Outcome Description:


Principal Investigator

Dr. Jeffrey N Martin, MD, MPH

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, San Francisco


United States: Institutional Review Board

Study ID:

NIH/NCI Grant #: R01 CA119903



Start Date:

April 2007

Completion Date:

July 2012

Related Keywords:

  • Kaposi's Sarcoma
  • HIV Infections
  • Kaposi's sarcoma
  • KSHV
  • AIDS
  • HHV-8
  • treatment naive
  • HIV Infections
  • Acquired Immunodeficiency Syndrome
  • Sarcoma, Kaposi
  • Sarcoma