In its chart, Abbott claims that Norvir is the least expensive of all the HIV protease inhibitors. This is "false and misleading" and in violation of government regulations, the FDA said in a warning letter to the company on June 10. The FDA notes that the Norvir cost listed is for a partial dose of the drug, while the costs of the other drugs are for full doses. (The smaller dose is not used for treating HIV, but to boost the levels of other antiviral drugs.) Moreover, the chart does not explain that Norvir can only be taken in combination with other HIV drugs. The FDA noted that the information "raises significant public health and safety concerns" for the HIV community because it's referring to a sub-therapeutic dose. Moreover, the chart "minimizes the risks of Norvir."
"Our data and others' provide increasing evidence that several regimens of antiretroviral therapy are safe, effective and well-tolerated during years of administration when started in infancy," the report noted.
The study also found that the children's viral load drop was greater when they were given a triple combination of medications from different drug classes, rather than using two drugs from only one class. This is the same as for adults.
Sixty-percent of the children who started therapy "early" had less than 400 viral load (undetectable) out to 200 weeks (approximately four years).
This compared to a third (30%) of the children in the so-called "delay" group.
In this study, the triple combination drugs used were Retrovir (AZT), Zerit, Epivir, Viramune or Viracept. (Retrovir and Zerit cannot be taken together.) The dual drugs used were from the nucleoside analogs class of medications (Retrovir, Zerit and Epivir). The researchers wrote that "treatment-associated adverse effects were infrequent."
The results from this group of 52 children, from 25 centers in the U.S. and Puerto Rico, were published in the June 16 issue of the New England Journal of Medicine. The study continues, and the researchers hope to get a better idea of the best time to start therapy in children.
French researchers teamed up with Doctors without Borders (officially called Medecins san Frontieres) to study a three-in-one combination of Zerit, Epivir and Viramune. The fixed-dose combination (FDC) pill, called Triomune, is made by Cipla in India, and is widely used in Africa. (Foreign companies successfully combine the active ingredients of HIV drugs from different companies, which is not done in the developed countries due to competition and until recently a refusal to work together. Gilead Sciences and BMS recently announced plans to combine Viread/Emtriva and Sustiva into one once-a-day pill.) Generic drugs are not necessarily as effective as their branded counterparts. They must be studied to prove effectiveness.
Sixty patients in Cameroon took one pill twice a day. After 24 weeks, 80% had less than 400 viral load (undetectable).
"Generic fixed-dose combinations of such regimens are widely regarded as crucial for scaling-up AIDS treatment in developing countries," the researchers noted. "These treatments improve adherence owing to the fewer daily doses relative to individual formulations. Supply, storage, and distribution are also easier because the range of products is smaller. Generic drugs are generally much cheaper than brand-name formulations."
They also reported that, "Despite wide intersubject variability of the plasma concentrations of the three drugs in the fixed-dose combination, the ranges were as expected and consistent with those previously described for the approved drugs." The study was published in the July issue of Lancet. Triomune costs $20 per month in Cameroon, compared to $35 for the brand name drugs with pharmaceutical company discounts. The brand names would be six pills (three twice a day).
In a commentary in the Lancet, Dr. N. Kumarasamy, the principal investigator for the U.S. National Institutes of Health (NIH) trials in Chennai, India, discussed the benefits and problems of providing HIV antivirals in resource poor countries, and concluded that, "Starting, monitoring, and managing the toxicities of antiretroviral drugs is an art and needs tremendous experience and dedication. Physicians need to be trained properly before we scale-up antiretroviral programs. We need to emphasize that physicians should adhere strictly to standard treatment guidelines to avoid antiretroviral failure and resistance which will be a future public-health challenge in the presence of increasing use of generic antiretroviral drugs."
In a small study conducted at the U.S. National Institutes of Health (NIH), researchers have shown that it may be feasible to treat HIV-infected patients with a simple, once-daily regimen of anti-HIV drugs given in pre-planned, 7-day-on, 7-day-off cycles. This approach is known formally as "short-cycle structured intermittent antiretroviral therapy" (SIT) or colloquially as the "7-7" approach.
"Our data suggest that the 7-7 approach, used with well-chosen drug regimens in settings where patient adherence is high, could be a powerful and cost-effective tool in treating HIV-infected individuals," says study author Mark Dybul, M.D., of the National Institute of Allergy and Infectious Diseases (NIAID), a component of NIH. "By using half as much antiretroviral medication, drug costs are reduced and drug-related toxicities may be less in the long run." He adds, "The 7-7 approach may have particular relevance to resource-poor countries around the world."
Dr. Dybul, NIAID Director Anthony S. Fauci, M.D., and their colleagues report their findings in the June 1, 2004 issue of the Journal of Infectious Diseases.
In their study, the NIH investigators enrolled eight HIV-infected people who had been successfully treated with a combination of three or more antiretroviral drugs for at least 6 months. Upon enrollment, the patients began following a treatment regimen of 7 days without antiretroviral therapy, followed by once-daily treatment with the drugs didanosine (ddI) [Videx], lamivudine (3TC) [Epivir] and efavirenz [Sustiva] for 7 days, followed by 7 days off the antiretroviral drugs, repeating the off-on cycle for more than a year. One patient withdrew from the study for personal reasons at week 24; the other seven patients receiving the 7-7 regimen maintained undetectable levels of HIV in their bloodstream (<50 HIV RNA copies per milliliter) for 60 to 84 weeks. During this period, the study volunteers had no significant changes in their CD4+ T-cell counts, and no evidence of resistance to the antiretroviral drugs in their treatment regimen.
Unlike a previous NIH 7-7 study using a different drug regimen, the investigators did not observe transient "blips" during which bloodstream levels of HIV rise above detectable levels, a finding they attribute to the persistence of efavirenz in the blood throughout the 7-day-off-therapy cycle in the current study.
The authors note that strict adherence to the prescribed regimen in the 7-7 approach is necessary. Of note, the once-daily regimen used by Dr. Dybul and his colleagues may allow for enhanced adherence compared with the twice-daily regimen that the researchers used in a previous study.