by Enid Vázquez
Update from the IAS Conference
Key Research
Around the world
Circumcision and penis cleansing
Single-dose for new moms
Clinical research
Maraviroc vs. Sustiva
Experimental TMC-125
Apricitabine
A side effect profile ahead of time
For more information
Update from the IAS Conference
This year’s international IAS Conference on HIV Pathogenesis, Treatment and Prevention, held in Sydney, Australia in July, presented progress, as ever, in the treatment of HIV. In a year in which two entirely new types of drugs are expected to come to market and help turn AIDS around for many, other drugs continue moving forward in the treatment pipeline.
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Key research
Dr. Pedro Cahn of Argentina, president of the International AIDS Society (IAS), organizer of the conference, provided an overview for reporters.
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Around the world
On the global front, UNAIDS reports that the number of people from middle-income countries (like Mexico) and low-income countries who take HIV therapy almost doubled in 2005 alone. That year the United Nations General Assembly passed a resolution to make 2010 the target year for universal access—HIV treatment for all who need it and want it. “Meanwhile,” said Cahn, “research from several countries, beginning with Haiti, demonstrates that community-based programs can deliver ART [HIV antiviral drugs] effectively. An abstract report from Uganda will demonstrate the viability of this approach in Africa.”
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Circumcision and penis cleansing
Following reports showing that circumcision can cut the risk of HIV infection in half among heterosexual men in Kenya and Uganda, one of the follow-up reports at this conference was a modeling study calculating the need for substantial funding and experienced surgeons to conduct rapid development of this prevention technique in 14 sub-Saharan countries, where the epidemic hits the hardest worldwide. Furthermore, cost effectiveness analysis supports this endeavor. On the flip side, a study looking at cleansing of the penis immediately following sexual intercourse in uncircumcised men was associated with a higher risk of infection and should not be recommended.
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Single-dose for new moms
Recently published data noted, as has been previously reported, that women who take a single dose of Viramune (nevirapine) to prevent HIV infection to their newborn infant around the time of labor can usually take the drug again effectively six months following birth. There is tremendous concern about HIV developing drug resistance to Viramune when women take a single dose while in labor. In addition, two other IAS reports showed a greatly reduced risk of transmission through breastfeeding when mothers take triple-drug HIV therapy.
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Clinical research
Several reports covered drugs that are new, soon-to-be-approved, or in early development. New options are always needed and older options are constantly re-examined.
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Maraviroc vs. Sustiva
As Positively Aware went to press, Selzentry (maraviroc) was approved by the U.S. Food and Drug Administration (FDA). Part of the excitement around this particular new drug is that it’s a brand new type of HIV medication. Maraviroc is a CCR5 inhibitor, blocking HIV from latching on to a co-receptor (called “CCR5”) that it needs to enter a human cell. Here maraviroc’s effectiveness was about the same as a currently approved medication, Sustiva, in 48-week data. Under a required FDA analysis called “non-inferiority,” maraviroc was found to be non-inferior to Sustiva in getting study participants (around 360 patients on each drug) to less than 400 viral load, but was inferior in getting them to reach less than 50. More people stopped taking maraviroc than Sustiva because of ineffectiveness, but more stopped Sustiva because of adverse events and CD4+ T-cell counts (T-cells) went up more with maraviroc. Still, maraviroc has the benefit of being a new drug working in a different way, with a different viral resistance pattern, and a tolerable side effect profile. All of that gives maraviroc a place at the table, where new HIV medications are badly needed.
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Experimental TMC-125
TMC-125 (etravirine), a non-nucleoside analog drug—like Sustiva and Viramune—showed good results in people whose HIV had developed resistance to this category of medication. Like most newer HIV meds, TMC-125 was developed to provide options for people with drug-resistant virus. In the studies DUET-1 and DUET-2, participants had to have both non-nucleoside resistance as well as resistance to the protease inhibitor (PI) class of HIV drugs. They all received the new PI drug Prezista (darunavir) in addition to two nucleoside analog drugs of choice, plus Fuzeon (enfuvirtide), if they wanted. Fuzeon is a twice-daily injectible HIV drug used in advanced patients.
At 24 weeks, participants taking TMC-125 were much more likely to achieve undetectable viral loads. Percent of participants getting to less than 400 viral load was 74% vs. 51% of the placebo (fake drug) group in DUET-1 and 75% vs. 54% in DUET-2. As can be expected, the number of participants achieving less than 50 copies viral load was lower: 56% of the TMC-125 group vs. 39% of the placebo group in DUET-1 and 62% TMC-125 vs. 44% placebo in DUET-2. Side effects associated with TMC-125 included diarrhea, nausea, and rash. The incidence of adverse events was similar between the two groups, including discontinuation for this reason. The researchers reported that, “TMC125 is the first NNRTI to demonstrate significant and sustained antiviral benefit at week 24 in patients with NNRTI resistance.”
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Apricitabine
Although HIV therapy generally consists of a drug combination that has two nucleoside analogs in it and this class has many meds, the nukes have suffered setbacks due to toxicity and drug resistance. This makes new nukes welcome, but one hasn’t been in the research pipeline for a long time. Apricitabine (ATC) is a nucleoside cytidine analog in early development. A small group of around 50 individuals with drug resistance to the nuke Epivir (3TC) were kept on their drug combination or had the Epivir switched out and replaced with ATC. At the end of three weeks, viral load drops were seen in the people on ATC, but not those on Epivir (as you would expect). Tolerability was reported to be good. Again, stay tuned for further data.
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A side effect profile ahead of time
Ziagen (abacavir) is a potent nucleoside analog drug with usage limited by a potentially fatal hypersensitivity reaction (HSR) seen in around 8% of people who take it. Now Ziagen’s maker, GlaxoSmithKline, has proven the usefulness of a simple and inexpensive blood test that’s already on the market to predict whether someone will have the allergic reaction.
While many think that rash is the most common symptom of HSR, in fact, fever and other so-called constitutional symptoms are the most common. At a GSK meeting, two women said they had Ziagen HSR that was denied by their doctors because neither of the women experienced rash. GSK, in fact, recommends over-diagnosis of HSR, as when there may be other causes of symptoms, such as a flu or reaction to other drugs (like the rash associated with Sustiva or Viramune). Symptoms usually, but not always, include some combination of sudden fever, muscle ache, severe nausea, vomiting or abdominal pain, severe tiredness, respiratory symptoms (cough, difficulty breathing, and sore throat) and possibly mild rash. A key feature of HSR is that symptoms get worse with every dose. People often are feeling better by the time another dose is due and then get sick again with their new dose. The real problem is when HSR has not been diagnosed or recognized by the patient, and he or she renews taking Ziagen after a break in time. This is called “re-challenged,” and this is when HSR becomes much worse, and fatalities have been seen. HSR is seen within the first six weeks of taking Ziagen.
In a GSK-sponsored study, 2,000 individuals from more than 300 centers in Europe and Australia had the screening test done. They were divided into two groups. In half of them, people at risk of HSR according to the test were excluded from the study. In this half, not one person suffered HSR. In the other half, a look back at the screening results showed that those with diagnosed HSR all had been at risk for it. A skin patch allergy test, placing a Ziagen compound on the upper back to look for a reaction, confirmed HSR.
The risk factor looked at was the presence of the HLA-B*5701 allele. This is a genetic test, but absolutely no other aspect of the person’s genes is being looked for.
Ziagen is also a part of the combo HIV drugs Epzicom and Trizivir. Its main competitor drug, Viread (tenofovir), is also potent and tolerable, but is associated with potential kidney toxicity which might make Ziagen a better option for some people. Viread is also available in the combo HIV drugs Truvada and Atripla. As always, there’s plenty of room for most of the HIV drugs.
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For more information
Visit the conference yourself, so to speak, at www.ias2007.org. Also see www.aidsmap.org, and www.TheBody.com. Webcasts and podcasts are available.
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