First-line Treatment in Chronic HIV Infection

NULLFirst-Line Treatment in Chronic HIV infectionWhen should treatment be initiated ?Probably, one of the most challenging questions in antiviral therapy is and will remain the question of the ideal time point for treatment initiation. Despite the lack of clinical studies addressing the issue, there is wide agreement between experts that any symptomatic patient should be started on antiretroviral treatment. The most compelling argument for this recommendation is the patient’s motivation. There is perhaps no other medical intervention in internal medicine, where adherence is such a key issue for the long-term effect of the intervention. A patient who suffers from a medial condition associated with advanced HIV infection is more likely to adhere to treatment than a patient who does not experience any clinical signs of HIV. As Joe Eron pointed out In his comments, the only thing we know is, when it is too late for treatment, which is when symptoms arise that need additional treatment and make ART difficult to manage. In general, in a patient with a CD4 count below 350 should prompt clinicians to discuss the option of antiviral treatment with the patient. Of course, several factors will influence the final decision (see table). When CD4 approaches the magic CD4 level of 200, delay of treatmtent clearly results in increased risk of mortality (Hogg et al, JAMA, 2001;286:2568).If treatment is initiated, what is the best regimen Between the experts participating at this TEAM round there was least agreement on this point. Milos Opravil from Zurich pointed out the arguments to start with a PI-based treatment. The important points are: longest knowledge of effects and side effects and the high number of mutations required for resistance development. On the other side, convenience and excellent performance in clinical studies support the use of a NNRTI. Joe Eron pointed out, that the first head-to-head comparison of efavirenz vs. nevirapine is currently underway and we will see preliminary results in Barcelona. It appears that ritonavir-boosted PI regimens as well as efavirenz (and perhaps nevirapine) based treatment are among the most potent cornerstones of HAART. Little discussion was spent on the choice of the nucleosides. Joe Eron suggested combivir (AZT+3TC) based on convenience as well as tolerance. Only limited information is available on triple NRTI-regimens. Of course, tricivir has the great advantage of convenience (two tablets a day). Special choices for special circumstancesTreatment needs to be adapted to the daily life. For patients in a methadone maintenance program, a once daily regimen might be preferable. A patient with a psychiatric disorder would generally not be treated with efavirenz by some experts (due to central nervous side effects), but again, Joe Eron suggested that he would still treat a patient with a bipolar disease who is in a stable condition with this drug. Should treatment be intensifiedThis question was risen by the second case where blood viral load was not undetectable (but at low levels) after 12 and 16 weeks of treatment. Joe Eron pointed out, that – despite the logic behind the approach – no clinical study has yet demonstrated an advantage of intensified vs. standard treatment in this situation. One must realize, that complete suppression of blood viral load can take up to 24 weeks, as has been documented 1999 in a JCI paper by the group of Pantaleo in Lausanne, as Bernard Hirschel pointed out in his comment. How should treatment be monitoredMonitor for efficacy Of course, treatment should be monitored by the measurement of HIV-RNA in the blood. Ideally, we test after 4 weeks of antiviral treatment and viral load should have dropped by more than one log (usually 2). Then, further testing is suggested at least every 4 months. Ideally, patients have an undetectable HIV-RNA concentration after 16 Weeks of treatment, but this might take longer as mentioned above. Check patient motivation and adherence regularlyIn addition to HIV-RNA testing, physicians should regularly re-assess the patient’s motivation to continue treatment. Adherence remains critical throughout the treatment. However, is a long term event. Do not forget to check for long-term side-effects Once the first few weeks of treatment are past, most patients do not experience any significant side effects. However, one must carefully observe the patient for the development of long-term side effects. Very early, anemia or pancytopenia may develop. However, more subtle side effects are the slow development of lipodystrophy, metabolic disorders (hypoglycemia, hyperlipidemia) and polyneuropathy among others. Management of side effects will be the focus of next TEAM round session. Pietro Vernazza