The integrase inhibitor raltegravir (Isentress) may be an optimal choice for many HIV-positive people receiving 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) 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 – which may be the largest series analysing the effectiveness of antiretroviral therapy (ART) in people with HIV 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 centre between January 2001 and December 2012.
Most of the study participants (80%) were men and about half were white. Only people who made regular visits (at least twice in a six-month period) were included. The most common type of cancer was haematological malignancies such as lymphoma and leukaemia, accounting for 58% of all cases; 42% had non-Hodgkin's lymphoma, an AIDS-defining cancer. Amongst people with solid tumours, the most common was gastrointestinal cancer, in 31%.
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 optimised nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) 'backbones'.
Oncologists, pharmacists and infectious disease specialists reviewed regimens to minimise drug-drug interactions. ART efficacy was defined as absence of virological failure (HIV RNA >200 copies/ml for six months or more) or virological rebound (>200 copies/ml after viral suppression).
Raltegravir was the most commonly used antiretroviral drug amongst people with haematological malignancies. More people taking raltegravir (46%) were antiretroviral-naive at the time of cancer diagnosis.
Raltegravir was also favoured 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 alkaloids, anti-tumour 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 six times more likely, and those taking NNRTIs were nine times more likely, to achieve sustained HIV suppression compared with those taking protease inhibitor-based regimens, according to a multivariate analysis.
Side-effects were more than twice as common with protease inhibitors (35%) compared with NNRTIs (14%), which in turn caused more side-effects than raltegravir (3%). Mortality was also significantly higher amongst protease inhibitor or NNRTI recipients (46 and 36%, respectively) compared with raltegravir recipients (13%).
ART interruption was less common amongst raltegravir recipients (7%) compared with those taking protease inhibitors or NNRTIs (28 and 26%, respectively). Clinically relevant drug-drug interactions were seen only in people using protease inhibitors.
ART regimens that included protease inhibitors were the "least favourable" 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-positive patients with haematological 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.
Torres HA et al. Efficacy and safety of antiretrovirals in HIV-infected patients with cancer. 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Denver, abstract H-1255, 2013. View the abstract on the ICAAC website.
ICAAC/American Society for Microbiology Antiretroviral Drugs in HIV-infected Patients with Cancer. Press release. September 12, 2013.