November 18, 2002
This session was an enlightening illustration of some of the difficulties and controversies involved in HIV therapy. The use of complicated "real life" cases is extremely useful. Often the right answer to treatment decisions lies in physician experience rather than a direct interpretation of trial data.
Many issues were raised and discussed at this meeting. The use of 3TC (lamivudine, Epivir) in HIV therapy when the patient also has hepatitis B (HBV) risks the development of HBV resistance to 3TC. So many doctors would now use both tenofovir (TDF, Viread) with 3TC in this situation as some early data shows that tenofovir works against 3TC-resistant HBV.
Using d4T (stavudine, Zerit) and ddI (didanosine, Videx) together may carry a high risk of causing lactic acidosis and can be toxic to the liver. Nevirapine (NVP, Viramune) also potentially causes liver damage and so it's best not to use all three drugs together, which may increase the risks.
Efavirenz (EFV, Sustiva) has been shown in animal studies to cause damage to fetuses. Many HIV drugs have not been tested in this way. Since efavirenz has been tested, current advice states that women should avoid pregnancy while using efavirenz. Anecdotally, however, women who have accidentally become pregnant while on efavirenz have decided to stay on it without any problems. The panel concurred that if this occurred in practice, the patient should make an informed decision based on the risk to controlling her HIV infection and the unknown risk of efavirenz to the fetus.
Structured treatment interruptions (STIs) were discussed and again the use of STI was considered only justifiable in the context of a carefully controlled clinical trial. The use of STI in very advanced HIV disease does risk the onset of illness while off therapy.
Adherence to therapy is crucial but in some circumstances impossible. Treatment simplification and the use of therapies with fewer side effects and toxicities are improving the situation. The use of specialist nurses and pharmacists, involvement of drug and alcohol dependency units, if there is a history of substance use, and the involvement of patients in clinical trials may help with success. This multi-disciplinary approach to adherence is now advocated by most HIV treatment centers, but this difficult field requires much more research.
Kaposi's sarcoma (KS) is the most common cancer in HIV infection but can often be prevented and treated with HIV therapy alone. Recent work in mice has shown that protease inhibitors (PIs) may stop blood vessels growing in KS tumors. Unfortunately, the same work has not been carried out with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Since NNRTIs are used most often in initial therapy (with two nucleoside analogues) some doctors have worried that NNRTI-based therapy may not be as effective at clearing the KS. However, studies of patients with KS have shown that any HIV treatment will clear the KS and no one treatment is superior. Many doctors treating KS would choose therapy based on what would be best tolerated and adhered to and would not choose a PI preferentially.