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ICAAC 2013: Raltegravir Safest for HIV+ Patients on Cancer Chemotherapy

The integrase inhibitor raltegravir (Isentress) may be an optimal choice for many HIV positive people undergoing cancer chemotherapy, as it is highly effective and well-tolerated in this population, according to a poster presentation at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2013) this week in Denver.

A growing body of evidence indicates that people with HIV have a higher risk for several AIDS-defining and non-AIDS malignancies, but approaches for treating cancer in this population have not been extensively studied.

Harry Torres and colleagues from the University of Texas MD Anderson Cancer Center in Houston conducted a retrospective analysis of different antiretroviral regimens used by HIV positive adults receiving cancer treatment at their hospital.

The study -- whichmay be the largest series analyzing the effectiveness of antiretroviral therapy (ART) in HIV-infected patients undergoing cancer chemotherapy, according to an ICAAC press release -- looked at medical records of 154 eligible patients with any type of cancer seen at the center between January 2001 and December 2012. Most patients (80%) were men and about half were white. Only people who made regular visits (at least twice in a 6-month period) were included.

Participants received ART regimens that included a protease inhibitor (37%), a non-nucleoside reverse transcriptase inhibitor (NNRTI, 32%), an integrase inhibitor (only raltegravir was approved, 19%), or a combination of these (11%), along with optimized nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) "backbones."

Oncologists, pharmacists, and infectious disease specialists reviewed regimens to minimize drug-drug interactions. ART efficacy was defined as absence of virological failure (HIV RNA >200 copies/mL for 6 months or more) or virological rebound (>200 copies/mL after viral suppression).

Results

• The most common type of cancer was hematological malignancies such as lymphoma and leukemia, accounting for 58% of all cases; 42% had non-Hodgkin lymphoma, an AIDS-defining cancer.
• Among patients with solid tumors, the most common was gastrointestinal cancer, in 31%.
• More people taking raltegravir (46%) were antiretroviral-naive at the time of cancer diagnosis.
• Raltegravir was the most commonly used antiretroviral drug among people with hematological malignancies.
• Raltegravirwas also favored by people using high-dose steroids and specific anti-cancer medications including topoisomerase inhibitors, alkylating agents, and anti-metabolite drugs.
• No significant differences among antiretroviral classes were seen for people using other types of cancer therapy including cytotoxic agents, vinca alkyloids, anti-tumor antibodies, corticosteroids, or radiation therapy.
• Antiretroviral efficacy was similar for integrase inhibitors and NNRTIs (96% and 97%, respectively), both of which worked significantly better than protease inhibitors (65%).
• People treated with raltegravir were 6 times more likely, and those taking NNRTIs were 9 times more likely, to achieve sustainedHIV suppression compared with those taking protease inhibitor-based regimens.
• Side effects were more than twice as common with protease inhibitors (35%) than with NNRTIs (14%), which in turn caused fewer side effects than raltegravir (3%).
• Mortality was also significantly higher among protease inhibitor or NNRTI recipients (46% and 36%, respectively) compared with raltegravir recipients (13%).
• ART interruption was less common among raltegravir recipients (7%) compared with those taking protease inhibitors or NNRTIs (28% and 26%, respectively).

ART regimens that included protease inhibitors were the "least favorable" for HIV positive cancer patients, the researchers concluded. NNRTIs and integrase inhibitors had "comparable efficacy," but based on safety, integrase inhibitors -- that is, raltegravir -- "appeared to be the antiretroviral of choice" for HIV patients with hematological malignancies or those receiving various chemotherapeutic agents.

They recommended that prospective studies be done to further define toxicity profiles in HIV-positive cancer patients receiving chemotherapy, and such studies should aid the development of guidelines for treatment of this population.

9/13/13

Reference

HA Torres, V Rallapalli, A Saxena, et al. Efficacy and safety of antiretrovirals in HIV-infected patients with cancer. 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2013). Denver, September 10-13, 2013. Abstract H-1255.

Other Source

ICAAC/American Society for Microbiology. Antiretroviral Drugs in HIV-infected Patients with Cancer. Press release. September 12, 2013.