Data for this Review were identified by searches of Medline using the search terms “antiretroviral agents”, “cancer”, “HAART”, and individual drug names. Only papers published in English between January, 1990, and January, 2011, were included. Additional references were selected from relevant articles. Abstracts and reports from meetings were included only when they related directly to previously published work.
ReviewUse of antineoplastic agents in patients with cancer who have HIV/AIDS
Introduction
Treatment of patients who have HIV with highly active antiretroviral therapy (HAART) substantially restores immune function and reduces opportunistic infections, plasma viral RNA load, and morbidity and mortality from AIDS-related complications;1, 2 however, cancer is still a substantial problem in patients with HIV/AIDS. Kaposi's sarcoma, non-Hodgkin lymphoma, and invasive cervical cancer are not typical in adults who are immunocompetent, but are prevalent in those with HIV/AIDS; therefore these diseases are regarded as AIDS-defining cancers. Hodgkin's lymphoma, and anal, lung, and testicular germ-cell cancers do not have the same definitive association with HIV/AIDS and, as such, are deemed as non-AIDS-defining cancers when the patient is co-diagnosed with HIV/AIDS.
Non-AIDS-defining cancers have increased significantly with rises in life expectancy in patients with HIV/AIDS. In the Antiretroviral Therapy Cohort Collaboration,3 which examined 39 272 patients with HIV-1 who started antiretroviral therapy between 1996 and 2006, 1597 patients had a documented cause of death. Of these 1597 patients, 236 (15%) died from AIDS-defining cancers from 1996 to 2006, but the proportion of deaths caused by AIDS-defining cancers decreased from 21% (70/341) in 1996–99, to 13% in 2003–06. Although 189 patients (12%) died from non-AIDS-defining cancers during the same period, the proportion increased from 7% in (25/341) in 1996–99, to 15% in (96/624) in 2003–06. Similar patterns were noted when the 5-year cumulative incidence of cancer was assessed in 472 378 individuals with AIDS who were cancer-free at the time of diagnosis from 1980 to 2006.4 83 789 patients were assessed from 1980 to 1989 (before antiretroviral use), 213 029 from 1990 to 1995 (monotherapy or dual therapy with antiretroviral drugs), and 175 560 from 1996 to 2006 (HAART). The cumulative incidence of AIDS-defining cancers decreased from 18% (15 728/83 789) to 11% (23 603/213 029) to 4% (7570/175 560) over the three timeframes, and non-AIDS-defining cancers increased from 1% (1056/83 789) to 2% (4348/213 029) with no change noted from 1996 to 2006 (2911/175 560). Although no change was noted from 1990–95, to 1996–2006, the incidence of non-AIDS-defining cancers such as anal cancer, Hodgkin's lymphoma, and liver cancer did continue to increase in all timeframes.
Although the type of cancer that patients with HIV are diagnosed with might be changing, the need for treatment with concurrent antineoplastic agents and HAART is increasingly common. The potential of HAART to cause drug interactions is well documented;5, 6 however, little is known about the interaction potential of cytotoxic agents or targeted antineoplastic agents with HAART. In addition to interactions of pharmacokinetic drugs, overlapping toxic effects are also possible. Here we review potential pharmacological interactions and combinations of antiretroviral and antineoplastic agents in patients with HIV who are receiving HAART therapy.
Section snippets
Classes of antiretroviral drugs
Classes of antiretroviral drugs include nucleoside reverse-transcriptase inhibitors (NRTIs) or nucleotide reverse-transcriptase inhibitors (NtRTIs), non-nucleoside reverse-transcriptase inhibitors (NNRTIs), HIV-1 protease inhibitors, integrase strand-transfer inhibitors (INSTI), fusion inhibitors, and entry inhibitors including chemokine-receptor antagonists.7 All recommended HAART regimens include a minimum of three active drugs to prevent resistance, with initial regimens including
Antiretroviral therapy and anticancer treatment
Because patients with HIV continue to live longer and develop AIDS-related malignancies or non-AIDS-defining cancers, more information about how to treat patients with anticancer treatment will be needed. Drug interactions are one aspect, but overlapping toxic effects are also a concern. Several antiretrovirals, including didanosine, stavudine, and zidovudine, have substantial toxic effects and are therefore not used in first-line HAART regimens in developed countries.
Future of antiretroviral therapy and targeted anticancer treatment
The trend in development of anticancer drugs is to move from the use of cytotoxic chemotherapy, which is indiscriminate, to molecularly targeted agents, which are more selective at killing cancer cells.118 Because molecularly targeted agents tend to be associated with less myelosuppression and peripheral neuropathy than does cytotoxic chemotherapy, there might be fewer concerns about overlapping toxic effects with HAART; however, new anticancer agents are not without toxic effects.
The AIDS
Conclusion
Detailed guidelines for dose adjustment based on data from clinical trials are not generally available for anticancer and antiretroviral drugs that are used concurrently. We look forward to a time when data from prospective clinical trials will be available to guide clinical decision making. For now, clinicians and clinical investigators should be cognisant of the potential for any interactions that are inferred from knowledge of drug metabolism, and should make judicious treatment decisions.
Search strategy and selection criteria
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2021, Translational OncologyCitation Excerpt :For example, fosemprenavir and ritonavir, both CYP450 inhibitors, could result in sorafenib accumulation, and possible toxicity. Among antiretroviral drugs, atazanavir and indinavir have been associated with unconjugated hyperbilirubinemia secondary to glucuronidation by uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) inhibition, similarly to Gilbert's syndrome [143,85,142,156], and bilirubin is one of the parameter used for dose adjustment for sorafenib [108]. To address some of these issues, the AIDS Malignancy Consortium, a National Cancer Institute-supported clinical trials group, conducted a phase 1/pharmacokinetic study of the tyrosine kinase inhibitor sunitinib in combination with HAART in HIV-positive patients with cancer (AIDS Malignancy Consortium trial AMC 061) [144].