The emergence of multidrug-resistant virus presents a barrier to effective treatment for many patients with long-standing HIV infection.

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In the present pilot study, reported in the May 13, 2008, advance online edition of HIV Medicine, Spanish researchers evaluated the safety, immunological efficacy, and evolution in HIV-1 reverse transcriptase (RT) among 28 highly treatment-experienced patients with multidrug-resistant virus who had at least 1 thymidine analog-associated mutation (TAM) and the M184V mutation, which confers resistance to lamivudine (3TC; Epivir) and emtricitabine (Emtriva).

At baseline, 58% of patients were classified as having Centers for Disease Control and Prevention (CDC) stage C disease. The baselineCD4 count was 363 cells/mm3, while the nadir (lowest-ever) CD4 count was 112 cells/mm3.

All study participants were treated with the zidovudine/lamivudine/abacavir combination pill (Trizivir) plus tenofovir (Viread).

Results

• There was a sustained 24-week drop in viral load of 0.71 HIV RNA copies/mL (P<0.001).

• 10 of 28 patients (35.7%) achieving viral load < 50 copies/mL.

• The median 24-week decrease in CD4 count was 53 cells/mm3 and only 17 cells/mm3 when baseline CD4 count was < 350 cells/mm3.

• No evolution in RT mutations, TAMs, accessory mutations, or K65R were observed.

• No clinical progression was observed.

• 1 patient experienced a suspected abacavir hypersensitivity reaction.

• A lower probability of achieving viral load < 400 copies/mL was associated with the following factors:

• D67N mutation (P=0.007);

• D67N/M41L mutation (P=0.01);

• 3 or more TAMs (P=0.07);

• Viral load > 10 000 copies/mL (P=0.01).

• Mutations conferring zidovudine hypersusceptibility (Y181C, K65R, and L74V) did not improve virological or immunological outcomes.

• Better CD4 count outcomes were seen in patients without the M41L mutation (P=0.04) or with baseline viral load < 10 000 copies/mL (P=0.01).

Conclusion

Based on these findings, the study authors concluded, "A bridging regimen with Trizivir + Viread [zidovudine/lamivudine/abacavir + tenofovir] prevents significant immunological decline and may forestall viral evolution in HIV-1 RT despite persistent viral replication."

Lluita contra la SIDA Foundation. Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.

5/30/08

Reference

J Llibre, A Bonjoch, J Iribarren, and others (HIV Conference Call Study Group). Targeting only reverse transcriptase with zidovudine /lamivudine /abacavir plus tenofovir in HIV-1-infected patients with microlitertidrug-resistant virus: a microliterticentre pilot study. HIV Medicine. May 13, 2008 [Epub ahead of print].

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