Treatment of non-Hodgkin's lymphoma in the age of highly active antiretroviral therapy

The best way to manage HIV-infected people with NHL in the age of HAART has not yet been established. Concurrent HAART and chemotherapy or suspension of HAART are the two main options. Both strategies have risks and benefits.

In a review article, Dr Richard Little and colleagues recommended delaying or interrupting HAART during the period of high intensity chemotherapy. Dr Little gave several reasons for this recommendation:

• Drug-drug interactions.

• Additive toxicities.

• Inability to optimally administer medications.

According to Dr Little, the immediate survival of a person with NHL is dependent on the remission of the cancer. Consequently, optimal administration of chemotherapy is the priority. Interruption of HAART may be warranted given that anti-HIV drugs such as indinavir (Crixivan), ddI (didanosine, Videx / VidexEC), efavirenz (Sustiva) and nevirapine (Viramune) may reduce drug levels of some anti-cancer drugs. In addition, the protease inhibitors may slow drug processing and worsen side-effects. Dr Little argued that worsening side effects may lead to poor adherence and drug resistance to HAART, thus undermining the longer term outcomes for the patient.

Interrupting HAART in people with advanced HIV disease who are taking chemotherapy is not without risks. For instance, CD4 cell counts may drop suddenly due to overall suppression of T-cells by the anti-lymphoma drugs as well as increased HIV replication due to the withdrawal of HAART. Nevertheless, Dr Little argued that the benefits outweigh the risks. "Relatively brief uncontrolled HIV viraemia is unlikely to have unfavourable long-term immunologic or clinical consequences if appropriate opportunistic infection prophylaxis is used," he wrote.

In support of this approach to management, Dr Little cited a study of 23 people who suspended antiretroviral therapy for the duration of chemotherapy. Three-quarters were alive 23 months later, 70% had full remission of NHL, and CD4 T-cell recovery occurred within six to 12 months.¹

There are alternatives to interrupting HAART in HIV-infected people with NHL. These are:

• Continuation of HAART with close monitoring for drug tolerance and adherence.

• Modification of HAART to reduce likelihood of interactions and overlapping toxicities.

In support of concurrent HAART and chemotherapy, one small study reported no additional adverse side-effects during co-administration of HAART and chemotherapy. However, CD4 cell counts may decline during chemotherapy despite HAART, so there may be no apparent benefit in continuing HAART while taking chemotherapy. As mentioned in the treatment sections, chemotherapy plus HAART is producing high rates of complete remission and two-year survival in recent studies.