March 2001

Tenofovir decreases HIV RNA significantly

FOSTER CITY, Calif. - Tenofovir disoproxil fumarate (Tenofovir DF, Gilead) is associated with significant HIV RNA decreases, according to 24-week results from Study 907. Patients treated with tenofovir disoproxil fumarate had an HIV RNA decrease in mean DAVG₂₄ of -0.61 log₁₀ copies/ml, compared with -0.03 log₁₀ copies/ml in the placebo group. The results come from a phase 3 clinical trial designed to investigate the safety and efficacy of tenofovir disoproxil fumarate when used to intensify a stable background antiretroviral regimen in 552 treatment-experienced patients with HIV RNA levels of 400-10,000 copies/ml.

Patients enrolled in the multicenter study had to have received stable antiretroviral therapy for at least eight weeks prior to study entry. They were then randomized to receive either tenofovir disoproxil fumarate (one pill once daily) or placebo in addition to their current therapy. After 24 weeks of blinded, placebo-controlled testing, patients in either group were allowed to receive the study drug for the remainder of the 48-week study period.

At baseline, patients had a mean HIV RNA level of 3.36 log₁₀ copies/ml and a mean CD4 cell count of 427 cells/mm³. Prior to enrollment, patients had received antiretroviral therapy for a mean duration of 5.4 years. Baseline genotypic analysis of 253 patients indicated that 94% had evidence of protease inhibitor (PI) nucleoside reverse transcriptase inhibitor resistance mutations. Fifty-eight percent had PI resistance mutations, and 48% had non-nucleoside reverse transcriptase inhibitor resistance mutations.

Forty-five percent of patients treated with tenofovir disoproxil fumarate achieved HIV RNA reductions <400 copies/ml at 24 weeks, compared with 13% in the placebo group. Additionally, 22% of patients in the study drug group achieved HIV RNA reductions to <50 copies/ml, compared with 1% in the placebo group.

Researchers reported that the incidence of grade 3 and 4 laboratory abnormalities and clinical adverse events was similar between both groups. Six percent of patients in both groups discontinued the study.

HIVMA develops qualifications for physicians caring for HIV patients

ALEXANDRIA, Va. - The HIV Medicine Association (HIVMA) has provided California officials with guidance about what qualifies physicians to be specialists in HIV medicine. Under an amendment to state law, health plan members with HIV are entitled to have a physician with expertise in HIV medicine coordinate their overall health care.

To be an HIV-qualified physician, an individual should demonstrate continuous professional development through the clinical management of at least 25 patients with HIV within the last year and a minimum of 15 hours of HIV-specific continuing medical education per year (including a minimum of 5 hours related to antiretroviral therapy).

Additionally, recently trained infectious disease fellows or those recently certified or recertified in infectious diseases should be considered qualified providers for patients with HIV.

A copy of the policy statement is available at www.hivma.org.

Funds available under Ryan White CARE Act

WASHINGTON, D.C. - The Health Resources and Services Administration's HIV/AIDS Bureau recently announced availability of funds under its FY2001 Ryan White CARE Act Title III Planning and Capacity Building Grant Program.

The program provides funding to support eligible entities in rural and underserved areas and communities of color in their efforts to plan for the establishment of HIV primary health care services and/or develop, enhance and expand their capacity to provide HIV primary care services. There are two initiatives available under the grant program. Information is available at www.psava.com.

HIV p24 antigen test kit recalled

ABBOTT PARK, Ill. - Abbott Laboratories is recalling lot 71843M101 of HIVAG-1 Monoclonal HIV p24 Antigen Test Kit, because the product did not meet established specifications. The test is used in in vitro detection of HIV-1 p24 antigen and is intended as a screening test for donated blood and plasma as well as an aid in the diagnosis and prevention of HIV. The company became aware that the antibody to HIV (rabbit) component of the test kit does not meet the label claim for volume. The label component states that 27 ml of fluid is in the vial. However, the vials actually contain approximately 21 ml, making a false-negative result possible.

Lopinavir-ritonavir not associated with PI-resistant HIV

CHICAGO - Data presented here at the 8th Conference on Retroviruses and Opportunistic Infections indicate that antiretroviral treatment-naive patients treated with lopinavir-ritonavir (Kaletra, Abbott Laboratories) who experienced viral rebound did not have protease inhibitor (PI)-resistant HIV. Thirty-two percent of antiretroviral-naive patients treated with a nelfinavir (Viracept, Agouron)-based regimen who rebounded did have resistant virus.

Additionally, researchers noted less (42%) lamivudine (3TC, Epivir, GlaxoSmithKline) resistance in patients who rebounded on the lopinavir-ritonavir regimen, compared with patients taking the nelfinavir regimen (86%).

Study M98-863 is a randomized, double-blind study of 653 antiretroviral treatment-naive patients treated with either lopinavir-ritonavir or nelfinavir in combination with stavudine (d4T, Zerit, Bristol-Myers Squibb) and 3TC. Patients with viral loads >400 copies/ml at either week 24 or week 48 were identified and their viruses examined for HIV drug resistance.

In a separate study of viral isolates from 56 patients who had not taken lopinavir-ritonavir and had experience with at least two PIs, researchers evaluated cross resistance between lopinavir and other PIs. An analysis demonstrated that viruses with reduced susceptibility to lopinavir were more likely to maintain susceptibility to amprenavir (Agenerase, Glaxo Wellcome) and saquinavir (Invirase, Roche) than to ritonavir (Norvir, Abbott) and indinavir (Crixivan, Merck).

A separate analysis of isolates from five single or multiple PI-experienced patients with viral rebound on a lopinavir-ritonavir regimen showed that HIV with decreased susceptibility to lopinavir had only modestly reduced susceptibility to amprenavir. Viral isolates from three three saquinavir-naive patients with decreased susceptibility to lopinavir maintained susceptibility to saquinavir.