Impact of early HAART

Since 1996 HAART has had an enormous impact on the natural history of HIV infection. HAART usually involves triple therapy with two nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor. During the first 2 years of the widespread application of HAART there was a reduction in HIV related mortality, although this has since levelled out.12 43 There are problems with adherence, pharmacology, and toxic-ity, but 50-90% of patients on HAART achieve sustained suppression of the virus and most patients show low persistent viral replication. Unfortunately, the viral mutation rate is such that viral genomes with each possible nucleotide substitution can be generated daily in an infected host, making the speed with which drug resistant HIV mutants can arise extremely rapid.43 This has led to predictions that about half of all patients may develop resistance to current treatments.43 44

The success of HAART has led to a reappraisal of the role of prophylaxis for opportunistic infections such as PCP, CMV, and M avium. This is due to the decreased risk of opportunistic infections in the face of a reduced viral load and sustained or increased CD4 T cell levels, and because of problems of drug interactions between HAART and prophylactic therapies.4 15-20 45-48 The Adult/Adolescent Spectrum of HIV Dis ease Cohort Study showed a decrease of 55% in opportunistic infections including PCP, CMV, and M avium between 1992 and 1997.49 The EuroSIDA study (a prospective study involving about 7300 patients) looked at the risk of opportunistic infections or death for patients on HAART. Patients with CD4 counts that consistently rose from <200 cells/mm3 to >200 cells/mm3 on HAART were substantially protected against opportunistic infections compared with patients with CD4 counts persistently below 50 cells/mm3 (3.7-8.1 v 72.9 episodes per patient year).50 There is evidence to suggest that HAART is associated with improved early survival from PCP (odds ratio 0.2).26 Patients with bacterial pneumonia or PCP were admitted to the ICU less frequently following the introduction of HAART in 1996.31 The optimal timing for the introduction of HAART in patients with PCP is not known. Cases of severe acute respiratory failure have been described following the early introduction of HAART (1-16 days after the diagnosis of PCP) who recovered after HAART interruption or steroid reintroduction.51 This phenomenon could be due to rapid recruitment of competent inflammatory cells responding to persistent pneumocystitis cysts.

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