Quadruple NtRTI Regimen Not Suited for First-Line HIV Treatment

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Quadruple NtRTI Regimen Not Suited for First-Line HIV Treatment

A four-drug regimen of nucleo(t)side analog reverse-transcriptase inhibitors (NtRTI) is less effective than standard combinations for first-line management of HIV, according to results of a multi-center randomized trial. Researchers made these observations while evaluating alternatives to the standard combinations.

"We do not recommend zidovudine/abacavir/tenofovir/emtricitabine for use in HIV-infected patients commencing first-line therapy when options for more conventional regimens are accessible," Dr. Rebekah Puls from the University of New South Wales, Australia, and colleagues write in their August 24th online report in Clinical Infectious Diseases.

The standard multi-class regimens may not be suitable in patients with tuberculosis coinfection or pregnant women, the researchers clarified. However, "class-sparing regimens may achieve maximal virologic suppression and thus may prevent resistance development," they hypothesized.

In their open-label study "Altair," Dr. Puls and her team evaluated the efficacy of two standard regimens and one quadruple NtRTI regimen in 322 treatment-naive uncomplicated HIV-positive adults.

Their baseline viral RNA load was greater than 2000 copies/mL and mean CD4+ counts were higher than 200 cells/ uL. The endpoint was a change in viral load after 48 weeks of treatment.

Patients were randomized to receive one of the following in addition to the NtRTI combination tenofovir-emtricitabine: 114 patients in group1 received efavirenz; 105 subjects in group 2 received ritonavir-boosted atazanavir, while the remaining 103 in group 3 received zidovudine/abacavir.

In view of the unsatisfactory response, patients in group 3 were shifted to other regimens after 48 weeks.

After 48 weeks of treatment, the decline in HIV RNA count was least in group 3 with a mean of 2.39 log10 copies/mL. The mean reduction in groups 1 and 2 were 2.59 and 2.67 log10 copies/mL, respectively.

The HIV RNA counts fell to < 200 copies/mL in 95% of patients in group 1, 96% in group 2 and in only 82% of patients from group 3, the quadruple NtRTI group, the researchers observed. The difference between group 3 and the others was statistically significant.

Virologic failures and adverse effects were significantly more frequent in the quadruple NtRTi group. Dr. Puls team also isolated the K65R mutation, which conveys resistance to many NtRTIs, from one of the treatment failures in group 3.

"Quadruple NRTI regimens have been tested and found to be associated with toxicities -- they are not recommended or used clinically," Dr. Roy Gullick, Chief of the Division of Infectious Diseases at Weill Medical College of Cornell University, New York, told Reuters Health.

"There are more effective regimens available than NRTI-only regimens, including NNRTI, protease inhibitor, integrase inhibitor and CCR5 antagonist regimens," Dr. Gullick said.

Clin Infect Dis. Posted online August 24, 2010. Abstract

http://www.medscape.com/viewarticle/728062