FDA Notifications

Combination lamivudine and tenofovir tablet approved

On Nov. 5, 2009, using expedited review procedures developed to support the President's Emergency Program For AIDS Relief (PEPFAR), the Food and Drug Administration (FDA), granted tentative approval for lamivudine and tenofovir disoproxil fumarate fixed dose combination tablets, 300mg/300mg.

The fixed dose combination product, indicated for use in combination with other antiretrovirals for the treatment of HIV-1 infection, is manufactured by Hetero Drugs Limited of Hyberdad, India.

The FDA's tentative approval of this product means that while FDA cannot fully approve the product for sale in the United States because of existing patent protections, it has been shown to meet all of FDA's safety, efficacy and manufacturing quality standards. Tentative approval qualifies the product for purchase using PEPFAR funds.

Fixed dose combination products like this one can help ease pill burden and simplify therapy, and may help increase adherence to therapeutic regimens, potentially reducing development of resistance to the separate drugs. Fixed dose combination products can help also help reduce costs associated with treatment for HIV infection.

Lamivudine and tenofovir are Nucleoside Reverse Transcriptase Inhibitors (NRTIs).

Pediatric dosing recommendations revised

On Nov. 6, 2009, the Food and Drug Administration (FDA) approved revised pediatric dosing recommendations that expand dosing to include children starting treatment at four weeks of age.

The revised label contains the following recommendation:

  • The recommended dosage in pediatric patients 4 weeks of age and older and weighing ≥4 kg is provided in Table 1. Zidovudine (Retrovir®) Syrup should be used to provide accurate dosage when whole tablets or capsules are not appropriate.
  • Table 1: Recommended Pediatric Dosage of zidovudine: Body Weight (kg) Total Daily Dose Dosage Regimen and Dose b.i.d. t.i.d 4 to < 9 24 mg/kg/day 12 mg/kg 8 mg/kg ≥ 9 to < 30 18 mg/kg/day 9 mg/kg 6 mg/kg ≥ 30 600 mg/day 300 mg 200 m.

ART guidelines for adults & adolescents are revised

On Dec. 1, 2009, the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents were revised to reflect the following changes. You can find the complete, revised guidelines on the AIDSinfo web site.

What's New in the Adults and Adolescent Guidelines Document?

The following key changes were made to update the Nov. 3, 2008, version of the guidelines:

• New Section: Based on interests and requests from HIV practitioners, a new section entitled "Considerations in Managing Patients with HIV-2 Infection" has been added to the guidelines. This new section briefly reviews the current knowledge on the epidemiology and diagnosis of HIV-2 infection and the role of antiretroviral therapy in the management of patients with HIV-2 mono-infection and HIV-1/HIV-2 coinfection.

• Key Updates: Drug Resistance Testing - In this revision, the panel provides more specific recommendations on when to use genotypic versus phenotypic testing to guide therapy in treatment-experienced patients with viremia while on treatment.

Genotypic testing is recommended as the preferred resistance testing to guide therapy in patients with suboptimal virologic responses or virologic failure while on first or second regimens (AIII).

The addition of phenotypic testing to genotypic testing is generally preferred for persons with known or suspected complex drug resistance mutation patterns, particularly to protease inhibitors (BIII).

• Initiation of Antiretroviral Therapy: In this updated version of the guidelines, the panel recommends earlier initiation of antiretroviral therapy with the following specific recommendations:

- Antiretroviral therapy should be initiated in all patients with a history of an AIDS-defining illness or with CD4 count < 350 cells/mm3 (AI);

- Antiretroviral therapy should also be initiated, regardless of CD4 count, in patients with the following conditions: pregnancy (AI), HIV-associated nephropathy (AII), and hepatitis B virus (HBV) coinfection when treatment of HBV is indicated (AIII);

- Antiretroviral therapy is recommended for patients with CD4 counts between 350 and 500 cells/mm3. The Panel was divided on the strength of this recommendation: 55% of Panel members for strong recommendation (A) and 45% for moderate recommendation (B) (A/B-II);

- For patients with CD4 counts >500 cells/mm3, 50% of Panel members favor starting antiretroviral therapy (B); the other 50% of members view treatment as optional (C) in this setting (B/C-III);

- Patients initiating antiretroviral therapy should be willing and able to commit to lifelong treatment and should understand the benefits and risks of therapy and the importance of adherence (AIII). Patients may choose to postpone therapy, and providers may elect to defer therapy, based on clinical and/or psychosocial factors on a case-by-case basis.

• What to Start in Antiretroviral-Naïve Patients: Increasing clinical trial data in the past few years have allowed for better distinction between the virological efficacy and safety of different combination regimens. Instead of providing recommendations for individual antiretroviral components to use to make up a combination, the Panel now defines what regimens are recommended in treatment naive patients.