There are two major decisions that have to be made early on in the management of HIV infected patients. The first is when to commence antiretroviral therapy (ART), and the other is what to use when treatment is initiated. Another vital consideration is the duration of treatment.

A paper originating from St Mary’s Hospital in London presented evidence that short-course antiretroviral therapy (SCART) in primary HIV infection provides patients with a viable alternative to commencing long-term ART.

SCART has the additional benefits of avoidance of long-term toxicity and development of drug resistance with the potential application to resource-poor settings where long-term treatment is not desirable.

Sarah Fidler said in her presentation that a study of 45 subjects indicated that early SCART was safe and was associated with preservation of HIV-specific immune responses which would be lost if no intervention was instituted. She ended by saying that a long term randomised trial is now needed.

The session on the choices faced by the clinician over which combination of drugs to use showed the dizzying range of options available. The presenters of the papers were all experts in the field and a leap of thinking was necessary to put oneself in the place of an average physician, with limited experience, attempting to find the triple- or quadruple therapy appropriate for a patient.

The presenters of the papers in the session titled “Initial therapy” examined various combinations and switches of modalities which embraced the nucleoside reverse transcriptase inhibitors (NRTIs), the non-nucleoside reverse transcriptase inhibitors (NNRTIs), the protease inhibitors (PIs) and the possible combinations of all three.

Two HAART sequences were compared in a study conducted in Barcelona, in which, said presenter Josep Mallolas, the use of two NRTIs and one PI, or two NRTIs and one NNRTI, resulted in comparable efficacy and tolerability in naïve HIV-infected patients. The subjects were ART-naïve patients with CD4 counts of below 500 c/mL.

Efavirenz (EFV) was compared with PI-based therapy in a study presented by J Arribas of Madrid. The patients enrolled were severely immunosuppressed, with a high rate of AIDS-defining conditions. The study showed that there were no differences in efficacy between the EFV and PI-based therapeutic modalities.

Comparisons of two more combinations of drugs were presented by Ole Kirk from Denmark and John Bartlett of the USA. Kirk presented the results of a comparison of a nelfiravine/nevirapine combination (N/N) with a ritonavir/saquinavir combination (R/S) in PI and NNRTI-naïve patients.

Both were combined with NNRTIs and patients were followed for 48 weeks. Results indicated that the N/N plus 2 NNRTIs was well-tolerated and was the more effective combination, but Kirk said in closing that more extensive follow-up should be performed before this treatment can be recommended for general usage.

John Bartlett presented the preliminary 48-week results of a comparison of abacavir/lamivudine (ABC/3TC) in combination with EFV, amprenavir/ritonavir (PI), or stavudine (NRTI) in the CLASS study. The full study is due to last 96 weeks. The eligibility criteria stated that the patients should have a viral load of > 5000 copies/mL and a CD4 cell count greater than 50c/mL. Second line ART was defined for cases of virologic failure or toxicity.

All three regimens suppressed viral load to < 50 copies /mL in at least 70% of subjects at week 48, supporting the potency of ABC/3TC when combined with NNRTI, PI or NRTI. Continuing follow-up is expected to provide long-term data on successful approaches to initial ART.

Some of the studies came in for criticism as their statistical power was questioned. Comments from the floor indicated that delegates felt that some of the conclusions were not well-substantiated, and that further or longer trials are necessary.

The bewildering array of possible treatments was highlighted by Daniel Kuritzkes, who titled his talk, “Beginning antiretroviral therapy: a world of options.” There are now 16 ART agents approved by the FDA.

Factors which should be considered when choosing an appropriate drug should include: potency, convenience (patients prefer fewer doses, and once-daily doses of multiple drugs are available), resistance potential (resistance emerges first in the most “fragile” drugs such as 3TC and the NNRTIs), the relationship between adherence and resistance (this needs re-examination), and cost – particularly important for developing countries.

In resource-poor countries, wherever possible, treatment initiatives should be linked to studies to determine the best options, said Kuritzkes.

AIDS 2002 Conference News produced by Health & Development Networks/Key Correspondent Team