Treatment Guidelines
A summary of the US Department of Health guidelines[12] of when to start and what combination of drugs to choose from follows.
Recent data has provided the basis for using the CD4 cell count as the major determinant because there is an increased mortality in patients with CD4 below 200. Treatment is therefore indicated in all patients with a CD4 count <200 and in symptomatic patients (i.e., all patients defined with AIDS according to 1993 Centers for Disease Control and Prevention classification as well as patients with wasting, thrush, or unexplained fever for >2 weeks). However, there is a lack of data to define at which level above CD4 >200 antiretroviral therapy is best started in asymptomatic patients. Some asymptomatic patients with a CD4 count >350 have high pretreatment viral loads (>50,000-100,000), which is another predictor of clinical progression. This is an area of controversy with some experts recommending treatment. Treatment decisions for all patients need to be individualized and take into account diverse factors such as CD4 cell count and rate of decline, viral load, patient interest in and potential to adhere to therapy, individual risks of toxicity, drug interactions, as well as the risks and benefits of early vs. late initiation of treatment. Adherence is a key determinant requiring 90%-95% of doses taken for optimal viral suppression.
Current treatment is unable to eradicate HIV so the aims are maximal inhibition of viral replication, restoration and/or preservation of immunologic function, improvement in quality of life, and reduction in HIV-related morbidity and mortality. This has to be weighed against accompanying problems of expensive regimens with sizable pill burdens or complicated dosing schedules, drug-specific toxicities, potential drug-drug interactions, viral resistance, and emerging long-term complications, especially lipodystrophy and metabolic changes.
There are at least 16 antiretroviral agents approved for the treatment of HIV infection. Others are available through expanded-access programs, enabling a large variety of potential combinations. No data exists to demonstrate the superiority of one regimen over another. Physicians should bear in mind that the first regimen affords the best opportunity for longterm control of viral replication; however, the mantra of individualization of therapy cannot be overemphasized. This is a complex area requiring management by specialists in the field. Initial combination regimens include two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor (PI), two NRTIs plus a non-nucleoside reverse transcriptase inhibitor (NNRTI), or three NRTIs.
These drugs can be used singly or in combination with low-dose ritonavir as a boosted regimen that increases trough levels, minimizing opportunities for viral replication and potentially allowing for activity against moderately resistant strains of virus. Boosting also affords a more convenient regime in terms of pill burden, scheduling, and eliminating food restrictions. Hepatotoxicity is well recognized with PIs, especially ritonavir.
An NNRTI-based regimen can be as effective as a PI-based regimen with the additional advantage of sparing PIs for a later date. Hepatotoxicity may be caused by both, but the risk with nevirapine is twice that of efavirenz after adjustment for PI use and hepatitis C virus coinfection.[13] An advantage of efavirenz is its once-daily dosing, but central nervous system side effects can cause hyperexcitability, vivid dreams, mood disturbances, and personality changes. Both may cause skin rashes.
Most evidence is with regimens incorporating abacavir. Advantages of this regimen include a twice-daily schedule, low pill burden (available in a fixed-dose combination), few toxic effects, and lack of undesirable pharmacokinetic interactions. There is the added bonus of saving two classes of drugs for use at a later date. Hypersensitivity reactions to abacavir can occur in 5% of patients.[14] This regimen is not considered as effective with high baseline viral load or with low CD4 counts.
Use of antiretroviral agents as monotherapy is contraindicated except in certain circumstances like pregnancy, to reduce perinatal transmission, or when there are no remaining options.
New drug development continues with increasing combined formulations, oncedaily/ sustained-release preparations, PIs with improved lipid-altering profiles, and new targets such as fusion/integrase inhibitors. Table 1 , Table 2 , Table 3 and Table 4 summarize the International AIDS Society-US Panel guidelines.[15]
© 2004 Le Jacq Communications, Inc.
Cite this: HIV Revisited: The Global Impact of the HIV/AIDS Epidemic - Medscape - May 01, 2004.
