1st International AIDS Society Conference on HIV Pathogenesis and Treatment Buenos Aires, Argentina - July 8-11, 2001

Oral Session

Different issues should be taken into consideration in order to select the first antiretroviral approach. We know that the emergence and proliferation of drug-resistant HIV during HAART is a major cause of treatment failure and viral load rebound. Insufficiently suppressive plasma drug concentrations, secondary to poor adherence (patients are usually poorly informed about the strict adherence required for a successful antiretroviral therapy), pharmacokinetic factors or adverse drug-drug interactions, permit residual viral replication in the presence of selective drug pressure and favor the emergence of resistant strains. Unfortunately, once resistance mutations develop there is a risk for cross-resistance in the same antiretroviral class to which resistance has emerged.

For a durable anti-HIV response we need to provide a comfortable dosing schedule. Until recently, many HAART approaches were quite problematic for some patients due to a requirement of thrice daily dosage. However all currently available anti-HIV treatments are scheduled BID which allows an easier adherence. When sufficient information and support are given to introduce medication as a habit, the dosing regimen either once or twice a day, and the number of pills does not significantly influence adherence.

The success of an overall treatment strategy depends on the optimal sequencing of regimens in response to the emergence of resistance virus. Selection of a first-line antiretroviral regimen is not only governed by the need for an effective, well tolerated and convenient treatment, but also the ability to leave subsequent treatment options as plentiful as possible should initial therapy fail (lack of cross-resistance). This demands long-term strategic thinking by the treating clinician.

When designing the first antiretroviral treatment we have to consider also cost, quality of life as well as certain individual peculiarities (type of work, risk behavior for HIV, and so on) for tailoring the best option.

There is a debate regarding whether a PI-based HAART is better, equal or worse as a first choice than a NNRTI-based HAART. In some settings one approach is going to be better than the other but probably at the end both strategies (PIs and NNRTIs) are quite similar whenever we provide each one to the appropriate individual.

For patients with very low CD4 cell count (< 100/mm³) and high viral loads (VL> 100,000 copies/ml) an approach with a high genetic barrier (PI based HAART) could be better as a first line treatment than an NNRTIs based ARV therapy (low genetic barrier). The risk for subsequent development of lypodistrophy (LD) depends on the prolonged use of NRTIs associated to PIs. Some specific NRTIs and PIs may produce a higher incidence of fat redistribution and/or lipoatrophy. Proper use of these drugs and selection of those associated with a lower risk of LD may reduce significantly this adverse effect. Subsequent switch of the PI by an NNRTI may reduced further the risk of lypodistrophy. Some PIs do not produce severe dislipemia while some NNRTIs may be associated with significant changes in the lipid metabolism. Additional issues like cross-resistance, viral fitness, local prevalence of primary resistances, long-tern toxicities should also be taken into consideration for selecting the first choice.

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