It is widely accepted that early recognition of virological failure in HIV patients with extensive drug resistance receiving salvage HAART is essential to avoid exposure to suboptimal regimens.

As reported in the May 28, 2008 online edition of AIDS Research and Human Retroviruses, researchers with the National Institute for Infectious Diseases in Rome, Italy, studied plasma viral load decline and rates of drug-resistance mutation accumulation in a prospective, 48-week study of 38 heavily previously treated patients receiving HAART guided by genotypic resistance testing.

The rate of viral load decline was studied by weekly determinations. To assess accumulation of drug-resistance mutations, serial genotypic resistance tests were performed for all treatment non-responders, defined as those who never attained a viral load < 50 copies/mL, or those with 2 viral load measurements > 50 copies/mL after prior suppression).

Results

• Over 48 weeks, 10 patients (26%) were non-responders.

• Use of less than 2 fully active drugs and having an elevated number of protease inhibitor and nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) mutations at baseline were strongly associated with virological failure.

• There was no evidence of a difference between responders and non-responders in changes in plasma viral load from baseline to weeks 1 and 2.

• In contrast, plasma viral load reductions from week 2 to week 3 and thereafter were significantly greater for responders compared with non-responders (P < 0.01).

• Among non-responders, the incidence rates per patient-month of emergent drug-resistance mutations were 0.67, 0.40, and 0.37 at weeks 4, 8, and 24, respectively.

Conclusion

"Having limited baseline resistance, receiving at least 2 fully active drugs, and showing constant plasma viral load reductions from week 2 to week 3 and thereafter were predictive of virologic response," wrote the study authors. In contrast, "early changes in plasma viral load levels were not."

Further, they noted, "Virologic failure was associated with detection of emergent drug-resistance mutations."

Finally, they concluded, "Virologic rebound in patients on salvage HAART should be addressed aggressively."

National Institute for Infectious Diseases, Rome, Italy.

6/06/08

Reference

V Tozzi, R Bellagamba, F Castiglione, and others. Plasma HIV RNA decline and emergence of drug resistance mutations among patients with multiple virologic failures receiving resistance testing-guided HAART. AIDS Research and Human Retroviruses. May 28, 2008 [Epub ahead of print].

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SM Badri and others. Utility of repeat genotypic resistance testing and clinical response in patients with three class resistance and virologic treatment failure. AIDS Patient Care and STDs. 21(8): 544-550. August 2007.

J Gatell and others. Efficacy and safety of atazanavir-based highly active antiretroviral therapy in patients with virologic suppression switched from a stable, boosted or unboosted protease inhibitor treatment regimen: the SWAN Study (AI424-097) 48-week results. Clinical Infectious Diseases 44(11): 1484-1492. June 1, 2007.

F Maggiolo and others. Effect of adherence to HAART on virologic outcome and on the selection of resistance-conferring mutations in NNRTI- or PI-treated patients. HIV Clinical Trials. 8(5): 282-292. Sept-Oct 2007.

J Mallolas and others. Inhibitory quotient as a prognostic factor of response to a salvage antiretroviral therapy containing ritonavir-boosted saquinavir. The CIVSA Study. HIV Medicine 8(4): 226-233. May 2007.

V Tozzi and others (Collaborative Group for Clinical Use f HIV Genotype Testing). Drug-class-wide resistance to antiretrovirals in HIV-infected patients failing therapy: prevalence, risk factors and virological outcome. Antiviral Therapy 11(5): 553-560. 2006.

A Canestri and others. Foscarnet salvage therapy for patients with late-stage HIV disease and multiple drug resistance. Antiviral Therapy 11(5): 561-566. 2006.

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