14th Annual Conference of the British HIV Association 23–25 April 2008, Belfast

EMERGENCE OF DRUG RESISTANCE IN HIV-1 INFECTED PATIENTS AFTER FIRST-LINE HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART): A SYSTEMATIC REVIEW OF CLINICAL TRIALS

HIV Med 2008; 9(Suppl. 1):3 (abstract no. O11)

RK Gupta¹, A Hill², A Sawyer³ and D Pillay^1
1University College, London, UK, ²Univeristy of Liverpool, Liverpool, UK, ³SEARCH, Thailand

BACKGROUND: Resistance to antiretroviral combination therapy is associated with increased mortality. Understanding the relative risks of resistance emerging to first-line therapy is of importance for both resource rich and poor settings.

METHODS: We undertook an overview of adult first-line HAART clinical trials using dual nucleoside reverse transcriptase inhibitors (NRTI) combined with a third agent: either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI). Main outcome measures were incidences of mutations conferring resistance to key drugs (NRTI, NNRTI, PI) per trial at Week 48. For meta-analysis, inverse-variance weighting was used to create estimates of overall incidences per group, with exact 95% confidence intervals.

RESULTS: Twenty clinical trials comprising 30 treatment arms and 7970 patients were included. Virological failure at 48 weeks occurred in 4.9% (3.9-6.1) of NNRTI versus 5.3% (4.4–6.4, p=0.50) of boosted PI recipients. Of failures genotyped, the M184V mutation (lamivudine resistance) occurred in 35.3% (95% CI 29.3-41.6%) starting NNRTI-based HAART versus 21.0% (14.4–28.8, p<0.001) for boosted PI. For K65R (multi-nucleoside resistance) in patients treated with non AZT-containing regimens, incidences were 5.3% (2.4–9.9) and 0.0% (0.0–3.6, p=0.01) respectively. One or more thymidine analogue mutations occurred in 1.5% (0.3–4.1) and 0.6% (0.0–5.8,p=0.627). Third agent resistance occurred in 53% (46–60) and 0.7% (0.0–5.5, p<0.001) respectively. These associations were also seen in Intent to Treat analysis.

CONCLUSIONS: Initial therapy with boosted PI-based regimens results in less resistance within and across drug classes, preserving more treatment options at time of virological failure.

2008-04-23
O11

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