Módulo 2 – Curso pós-graduado – VIH e Envelhecimento

Non-AIDS Defining Cancers Among HIV Infected People

Clinical Management of non-AIDS defining cancers

Autor: Prof. Doutor Vicente Estrada, MD PhD (Hospital Clínico San Carlos, Madrid, Spain)

Management of NADC

The management of non-AIDS defining cancer is challenging. Tumour staging may be affected by the presence of reactive lymphadenopathy or other imaging abnormalities. Response to treatment may also be affected by the presence of comorbidities, which may result in a poor performance status (eg, poor Karnofsky performance score index). In addition, many patients present with late-stage cancers, regardless of the type of NADC.

Treating both HIV and malignancy can be problematic, as chemotherapy combined with ART may increase cytotoxicity or cause other drug–drug interactions that may further enhance immunosuppression. This might be a cause of treat- ment disparities. HIV-infected individuals are less likely to receive treatment for some cancers than uninfected people, which may affect survival rates. For example, a US study showed that, from 2006 to 2010 (after HAART implementation), the odds ratio of HIV-infected patients not receiving an adequate treatment was 2.2 more times than with HIV- negative patients. Factors independently associated with lack of adequate cancer treatment included low CD4+ cell count, male sex with injection drug use exposure, age 45 to 64 years, black race, and distant or unknown cancer stage.

Drug-drug interactions can be related to problems in metabolism (by inhibition or induction of cytochromes, for instance), problems in the absorption (due to chelation or changes of gastric pH) or problems in the excretion (with the inhibition of renal drug transporters).

There are some ARV drugs that have a highest potential for interactions. For example, ritonavir or cobicistat-boosted protease inhibitors (PI) might inhibit cytochrome-P 3A4 (CYP3A4), and non-nucleoside reverse transcriptase inhibitors (NNRTI) are inducers or substrates of several CYP enzymes. Other drugs have moderate potential, such as rilpivirine that may be the victim of enzyme inhibition or induction, and that has impaired absorption when used with omeprazole and without food. This interactions may reduce the efficacy of chemotherapy or increase toxicity of ART, thus being advisable to select drugs without clinically relevant interactions, such as the integrase inhibitor RAL.

A stepwise approach to drug-drug interactions should be based in the following questions:

  • Is co-medication necessary? If it’s not, then you should stop it.
  • If it’s necessary, can you manage this interaction? In that case, a monitoring plan should be established and, if required, adjust dose ongoing or on completion of treatment.
  • If this medication is necessary and the interaction can’t be managed, are there other alternatives? If there are al- ternatives, it is advisable to change to another medicine with no interactions. When there are no alternatives, toxicities and adverse effects should be monitored, to minimize safety risks.

The website (www.hiv-druginteractions.org) of the University of Liverpool provides updated information about ARV drug interactions. The integrase inhibitors (dolutegravir and raltegravir) have the best profile of interactions with cytotoxic drugs. The risk of drug-drug interaction with dolutegravir is between moderate and low while raltegravir has a low potential for drug interactions. The reason for that is that raltegravir and dolutegravir have a metabolism related to the uridine 5’-diphospho-glucuronosyltransferase 1AA (UGT1A1) but dolutegravir also has a minor metabolism via CYP3A. Hence, integrase inhibitors and, especially raltegravir, may become the standard of care in patients receiving chemo- therapy and presenting multiple comorbidities, due to their reduced interaction potential as compared to NNRTI and PI.

In conclusion, the incidence of non-AIDS defining cancers is higher among HIV-infected individuals, which account for the majority of malignancies of these patients. Management of NADC requires a multidisciplinary approach, involving both oncologists and HIV physicians. Finally, drug interactions between anti-cancer and anti-HIV drugs are critical in the management of this condition.

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