16th International HIV Drug Resistance Workshop 12-16 June 2007, Barbados

EVOLVING WAVES OF SINGLE, DUAL AND TRIPLE CLASS RESISTANCE IN SAN FRANCISCO

Antivir Ther. 2007; 12:S45 (abstract no. 38)

S Blower ¹, R Smith¹, J Okano¹, E Bodine¹ and J Kahn^2
1David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; ²UCSF, San Francisco, CA, USA

BACKGROUND: Over the past twenty years in San Francisco single-, dual- and triple-class resistant strains of HIV have evolved. Here, we reconstruct and predict the evolution of single-, dual- and triple-class resistant strains in this city. We also address the question: has the evolution of multiple-drug-resistant (MDR) strains increased the severity of the epidemic? Finally, we identify key drivers of MDRHIV.

METHODS: We use a multistrain mathematical model to make our evolutionary predictions. Our model includes: transmitted resistance, acquired resistance, and amplified resistance (which is the result of salvage therapies). We model 25 years of evolution (1987–2012) of 80,000 strains; 10,000 wild-type strains and 70,000 resistant strains that vary in fitness and drug susceptibility. By using clinical, virological and behavioral data to estimate the value of the case reproduction number (R₀), we quantify the effect of MDRHIV on epidemic severity. We use Classification and Regression Trees (CART) to identify the key drivers of MDRHIV in San Francisco.

RESULTS: Our historical reconstructions, from 1987 to 2007, reveal the impact of the past three eras of treatment (i.e., eras of mono-, dual- and triple-therapy) on the complex evolution of drug resistance in San Francisco. Our reconstructions show complex waves of single-, dual- and triple-class resistance rising, falling, and finally stabilizing over the past 20 years. However, our predictions show MDRHIV levels are likely to decrease over the next 5 years. We estimate that R₀, in the era of triple therapy, equals 2.95 (median; interquartile range (IQR) 1.95–4.46) indicating that the evolution of MDRHIV has reduced epidemic severity; as we estimate that the pretreatment value of R₀ was 4.34 (median; IQR 2.85–6.63). Our CART analysis reveals that, surprisingly, the key drivers of MDRHIV are the viral load of individuals infected with wild-type strains who are either (i) not yet treatmenteligible, or (ii) untreated but treatment-eligible.

CONCLUSIONS: In San Francisco the severity of the epidemic has decreased since the introduction of therapy; levels of MDRHIV are likely to fall over the next five years. Initiating treatment earlier in individuals infected with wild-type strains could lead to sudden and dramatic decreases in levels of MDR.

2007-06-12
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