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
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%.
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
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
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.
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