"This is a very tough decision but I can't truly, in my heart, be convinced that there are enough data to support the safety or the efficacy of [adefovir dipivoxil] 60 mg," said Harlem Hospital's Dr. Wafaa El-Sadr at the FDA's Antiviral Advisory Committee's November 1st meeting reviewing Gilead's new drug application (NDA) for adefovir.
The FDA reviewed four controlled trials to establish the activity of adefovir 120 mg; one bridging study to evaluate the relative efficacy and safety of 60 mg versus 120 mg; and analyses on adefovir's safety (including the reversibility of nephrotoxicity) and its activity in NRTI-resistant patients.
'He actually said that Sustiva was better than Crixivan,' I overhead one leading HIV clinical investigator say in dismay at an Abbott sponsored cocktail party held during the Lisbon Conference. She was referring to a particular speaker, a Titan on the lecture circuit,
Each day, 1,600 infants are infected with HIV. While perinatal transmission has been reduced to only a few hundred cases a year in the US through the use of a lengthy course of AZT, the regimen, which costs $800, is far out of the reach of all but a lucky few who live in the developing world. Now, however, researchers from Makerere University in Kampala, Uganda and Johns Hopkins University in Baltimore have identified a simple and inexpensive method of preventing HIV transmission from mother to infant.
A central tenet of evolutionary theory is that species undergo genetic change over time. Given a particular environment, some of these genetic variants are more "fit" (that is, they are able to reproduce more effectively) than others, and they become dominant. Other variants are fit enough to survive and coexist with the dominant population.
A central tenet of evolutionary theory is that species undergo genetic change over time. Given a particular environment, some of these genetic variants are more "fit" (that is, they are able to reproduce more effectively) than others, and they become dominant. Other variants are fit enough to survive and coexist with the dominant population. Still others are so unfit that they are unable to reproduce, or they reproduce poorly, and eventually die out.
Although ddI (didanosine, Videx) is a highly potent nucleoside analog, it is associated with occasionally severe toxicities and can be difficult to take. ddI was initially approved for twice-a-day dosing, which by itself is not too demanding.
Since its approval, abacavir (Ziagen), a nucleoside analog, has been known to cause a severe hypersensitivity reaction in three to five percent of people who take it.
St. John's wort, an herbal dietary supplement, is popularly used to reduce depression and anxiety. However, the herb has been thought to induce the CYP3A4, which could have an effect on plasma concentrations of protease inhibitors and other drugs.
It is painfully evident that new antiretrovirals are needed to treat resistant virus when people are forced to construct a therapeutic regimen by recycling six, or worse yet, eight old drugs.
Considered to be the pre-eminent infectious disease meeting in the world, the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) was held in San Francisco this fall, from September 26 to 29, 1999. In the absence of a World AIDS Conference this year, this was the first major venue for HIV researchers and pharmaceutical companies to present their data since the Retrovirus Meeting last January.
Veronica Miller, PhD, from Frankfurt's Goethe University has been following a cohort of 94 salvage therapy patients on mega-HAART (Lisbon, Abstract 587). Preliminary information from this cohort has been previously discussed in Treatment Issues
The 39th ICAAC devoted significant attention to the HIV-associated adipose redistribution syndrome (HARS), the new umbrella term for the various body fat composition changes that have become a grave concern to many patients on HAART. The disorder has, accordingly, become the center of attention of antiretroviral drug developers, clinicians, marketing specialists and stock investors.
Post-exposure prophylaxis (PEP) is sometimes referred to as the "morning-after pill" for individuals with unanticipated sexual or injection drug related exposures to HIV. This is misleading, as PEP is not as simple as swallowing a single pill.
Perhaps no government program is more important to people with HIV than Medicaid. This state-federal partnership provides comprehensive health care to more than half the adults with HIV and virtually all the children. In 1998, Medicaid expenditures on HIV care totaled $3.8 billion, far more than any other government program.
Over the past few years, treatment options for people with HIV have expanded dramatically. As new antiretroviral treatment strategies improve the health of thousands of patients across the nation, the progress with AIDS research and new drug development is undeniable.
The Americans with Disabilities Act is a landmark piece of legislation that protects the disabled against discrimination in public places. It prohibits restaurants, health clubs, theatres, and medical facilities from turning the disabled away and requires all such facilities to make 'reasonable accommodations' for the disabled.
My name is John. I am 51 years old and have been living with HIV for approximately ten years now. I worked in the computer software industry for over 20 years before becoming disabled by AIDS six years ago. I began taking HIV medications back when a cocktail was still an alcoholic beverage and the only drug combination was AZT and AZT.
At the Centers for Disease Control's 1999 National HIV Prevention Conference in Atlanta, new data on AIDS deaths in the United States were released. In contrast with 1997, when a 42% decrease in AIDS deaths was reported, the decline from 1997 to 1998 was only 20%.
The 2nd International Workshop on Salvage Therapy was also the setting for a complete report on ACTG 359, the first randomized and controlled large rescue therapy trial. The study enrolled 277 volunteers (17% women) who had taken indinavir for more than six months (median of 14 months).
The greatest frustration in current care is that many, if not most, people cannot keep their viral loads down with the current medications. Sometimes inability to take the drugs consistently is the original culprit, but HIV's acquisition of drug resistance eventually becomes the critical problem.
The reasons why some individuals can engage in repeated high-risk sexual and drug-injecting activities without ever becoming HIV-positive have long eluded researchers. Several genetic and immunologic factors may come into play. Genetic defects in the cell receptors (the 32 unit deletion in the gene for the CCR5 chemokine receptor) that HIV uses when fusing with uninfected cells is a key to the HIV resistance in some, but by no means all, such persons.
Commercial preparations of human chorionic gonadotropin (HCG), a hormone secreted in abundant quantities during the first trimester of pregnancy, inhibit the growth of Kaposi's sarcoma (KS) in immunodeficient mice as well as in test tube cell cultures. HCG also attenuates human KS lesions when administered either locally or systemically. Recently, studies have shown antiviral effects in SIV-infected monkeys and transgenic mice containing certain HIV genes.
With the FDA accepting 48-week viral load data as sufficient for final approval of HIV medications, there is little knowledge of the long-term success rates of the new antiviral combinations, especially when the drugs move beyond clinical trials and out into the real world. The effects of these new treatments on disease progression, formerly considered the absolute standard for drug approval, have become a complete mystery.
Individual accounts of impotence after starting protease inhibitors abound in the community. The mainstream medical press has ignored the issue until this March, when Spanish doctors described 14 of their 260 HIV-positive patients who started having sexual difficulties from 2 to 20 months after starting a protease inhibitor regimen (Eduardo Martinez et al., The Lancet, March 6, 1999, pages 810-1).
In a test of his theory that patients given aggressive nutritional support and hormone replacement therapy would do better than those given standard care, Jon Kaiser, M.D., of The Wellness Center in San Francisco, performed a retrospective comparison study of 148 HIV-positive patients from two similar clinics (poster 184). Seventy-four patients from his practice were closely matched for age, sex, socioeconomic status, baseline CD4 counts and viral loads with patients from a nearby medical practice.
The 3rd International Conference on Nutrition and HIV Infection, held on April 22-25 in Cannes, France, marked a break from the previous two conferences. Its emphasis on lipodystrophy and the metabolic complications of highly active antiretroviral therapy (HAART) rather than AIDS-related wasting reflects the changing face of HIV infection and its treatment, at least in rich countries.
Just as HIV disease progression is highly variable, so too is the aftermath of successful suppression with the new highly active antiviral therapies (HAART). One disturbing newly emerging syndrome, commonly referred to as HIV-associated lipodystrophy (HAL) includes a vast constellation of body shape and metabolic abnormalities. Most symptoms fall into three main categories: The most obvious are altered fat deposits.
Although the U.S. is still far from guaranteeing universal access to HIV treatments to its residents, the situation here pales in comparison to that in the developing world. Sub-Saharan Africa has been hardest hit by the global AIDS epidemic, with rates of infection exceeding 30% in some regions, yet the drugs that have extended the lives of so many Americans are simply unavailable there.
The 6th Conference on Retroviruses and Opportunistic Infections reported considerable progress in eliminating mother-to-infant HIV transmission in this country, while the struggle to reduce such transmission in the developing world is only beginning. A major report at the conference concerned the PETRA Study, a multinational effort to assess the potency of regimens considerably shorter than the U.S. standard.
Five NNRTIs still under development were presented at the 6th Conference on Retroviruses and Opportunistic Infections. Currently the NNRTIs have cross-resistance to each other. A single mutation (K103N -- a lysine to asparagine at amino acid 103 in HIV's reverse transcriptase enzyme) can occur rapidly and negates the activity of all currently approved NNRTIs.
The Atlantic Study is a major ongoing multicenter European and North American trial directly comparing protease-containing and protease-sparing regimens. Preliminary 24-week data were presented at the 6th Conference on Retroviruses and Opportunistic Infections. Study participants receive d4T/ddI/ 3TC, d4T/ddI/ nevirapine or d4T/ddI/ indinavir in open-label fashion.
Thirteen antiretroviral agents are now approved for use in the U.S. Another, the protease inhibitor amprenavir, will probably receive approval in April, and as many as a dozen other agents will likely come before the FDA in the first half of the next decade.
The introduction of highly active antiretroviral therapy (HAART) has greatly expanded the potential of IL-2, a natural CD4 cell proliferation stimulant (see Treatment Issues, November 1996, pages 1-5). A few reports suggest that HAART plus IL-2 can reach the goal of cleansing the body of HIV.
Most people have heard of the "Berlin patient" by now. First reported in Treatment Issues in November 1997, he was later featured in The New York Times Magazine on June 21, 1998. This man, a patient of Dr. Heiko Jessen in Berlin, with the code name AA, has the first case of HIV infection publicly pronounced as "in remission" as a result of treatment.
GMHC Treatment Issues: January - Volume 13, Number 1
Many experts fear that treatment failure will be a growing problem since current antiviral regimens can control HIV replication without completely eliminating it. The implications of such "residual" replication for the evolution of drug resistance were a major point of discussion at the 12th World AIDS Conference this summer (see Treatment Issues, July/August 1998, pages 1-6).
Newly approved abacavir (Ziagen), the sixth nucleoside analog, promises to be one of the most potent antiretroviral agents available for treatment of HIV infection. Unfortunately, most of the pivotal trials and clinical studies using abacavir have focused on persons with early or intermediate disease and no prior treatment.
It might seem easy to define treatment failure and devise strategies to recover from it. But Keith Henry, M.D., who heads a clinic in St. Paul, Minnesota, for persons with drug-resistant HIV, observes, "Prescribing salvage therapy is at the level of anecdotal medicine.
The AIDS Clinical Trials Group, an offshoot of the National Institutes of Health, is conducting a series of second-line treatment studies in volunteers with significant viral loads despite nucleoside analog and, sometimes, protease inhibitor therapy.
This information is designed to support, not replace, the relationship that exists between you and your doctor.