New Prezista pill
New Prezista warning
U.S. treatment guidelines updated
ACTG 5202: Epzicom vs. Truvada
Lactobacillus for a healthy vagina
Chewing infant’s food can lead to HIV
Swiss experts say people with undetectable viral load and no STI cannot transmit HIV during sex
New Prezista pill
Good news—the new Prezista (darunavir) pill has been completed and given approval by the U.S. Food and Drug Administration (FDA). People on Prezista can now take one 600 mg tablet instead of taking two pills at 300 mg each. Either way, 100 mg of Norvir (ritonavir) must be taken with Prezista. The 300 mg tablets will continue to be available. The 600 mg tablets are expected in the pharmacy in mid-May.
back to top
New Prezista warning
A warning about liver toxicity has been added to the label of the blockbuster protease inhibitor Prezista. A Dear Healthcare Professional letter was also issued by manufacturer Tibotec Therapeutics with the FDA in March.
The “Warnings” section of the Prezista label now has updated information.
- In studies of Prezista/Norvir, drug-induced hepatitis (acute hepatitis, cytolytic hepatitis) was seen in less than half of one percent of people.
- After becoming commercially available, cases of liver injury, including deaths, have been seen.
- It has not been established that Prezista/Norvir was the cause.
- These cases generally occurred in people who 1) have advanced HIV disease and are taking other medications at the same time; 2) have hepatitis B or C; and/or 3) develop immune reconstitution inflammatory syndrome (IRIS).
- Liver function should be measured before starting Prezista/Norvir and increased monitoring should be considered for people with underlying chronic hepatitis, cirrhosis, or elevated levels of AST/ALT (lab measurements of liver function), especially during the first several months of therapy.
- No dose adjustment is required for people with mild or moderate liver impairment, but in people with severe hepatic impairment, Prezista/Norvir is not recommended.
- The incidence of adverse events or lab abnormalities was not greater in people with hepatitis B or C, except for increased hepatic enzymes (AST/ALT).
- Interruption or stopping therapy must be considered if an individual develops signs of new or worsening liver dysfunction, including medically significant elevations of liver enzymes and symptoms such as fatigue, anorexia (loss of appetite), nausea, jaundice (yellowing of the eyes and skin), dark urine, and tenderness or enlargement of the liver.
Prezista must be taken with a small booster dose of another protease inhibitor, Norvir, which is known to be liver toxic.
back to top
U.S. treatment guidelines updated
In January, the U.S. Department of Health and Human Services made changes to its HIV treatment guidelines. Added to the “preferred list” of medications to use in people taking HIV therapy for the first time was Invirase along with a small booster dose of Norvir, under the protease inhibitor drug class. Under the nucleoside analog drug class, Epzicom (a combination of Ziagen and Epivir) was moved up from the “alternative” list to the “preferred” one, if the individual first tests negative on HLA-B*5701, an inexpensive genetic test that only looks for whether or not a person is at risk of experiencing a hypersensitivity reaction to Ziagen. Also in that drug class, Combivir (a combination of zidovudine and Epivir) was moved down from the preferred list to the alternative list. In essence, Combivir was being traded for Epzicom, now that the safety of Epzicom is virtually assured with the proven effectiveness of the HLA test last year. See also below.
back to top
ACTG 5202: Epzicom vs. Truvada
The HIV meds Epzicom and Truvada are head-to-head competitors. Either one or the other, but not both, may be included in an HIV drug regimen. So the question for these two powerful drugs has been: is one better than the other?
In the sometimes rollercoaster world of HIV treatment, Epzicom was recently up and then rapidly down. First there was the good news that Epzicom had been added to the “preferred list” of U.S. guidelines at the end of January (see above), followed the next week by the negative news that Ziagen, one of the drugs contained in Epzicom, had been associated with heart complications (see page 27). A week later, there was more bad news.
A large, independent study found that in a subgroup of participants, people on Epzicom were not doing as well as those on Truvada. Although both groups did very well overall, the difference was statistically significant.
ACTG 5202, conducted by the U.S. AIDS Clinical Trials Group, compares Sustiva to Reyataz, taken with either Epzicom or Truvada. Although all groups saw very good results, Epzicom did not do as well as Truvada in those people who started the study with more than 100,000 viral load.
As a result, the study’s Data Safety Monitoring Board (DSMB) recommended that these participants be unblinded (let them know they were being given Epzicom and not Truvada). The study was unblinded for the people who started with more than 100,000 viral load, and participants on Epzicom could switch to Truvada or other medications, if needed, or, if doing well on Epzicom, given the option to switch if they desired.
In a conference call with community representatives of ACTG, study researcher Eric Daar, M.D., said it’s reassuring that “the overall response rate is really good for all people” and that study participants know their lab numbers so they can see how well they’re doing.
The DSMB also saw a quicker time to a Grade 3 (on a scale of one to five) adverse event in the Epzicom group, mostly malaise (generally feeling ill) and laboratory test abnormalities, such as increased blood levels of cholesterol and triglycerides. There were no problems with safety, however. The National Institute of Allergy and Infectious Diseases (NIAID), which funds the ACTG, reported that, “In general, these side effects were obvious to participants or the study physicians and would have been readily managed or treated.” The statement also noted that, “All regimens effectively reduced the amount of virus in most participants,” but that Epzicom’s being less effective was important to consider.
These findings are from a preliminary analysis. The study is ongoing and has more scientific data to uncover.
The ACTG findings came a week after Epzicom’s manufacturer, GlaxoSmithKline (GSK), presented 48-week data at CROI (see conference reports elsewhere in this issue) comparing Epzicom to Truvada, also with treatment-naïve individuals. The 96-week HEAT study found non-inferiority of Epzicom to Truvada. (“Non-inferiority” is a statistical standard imposed by the U.S. Food and Drug Administration.) The ACTG study, however, is much larger: nearly 2,000 participants compared to 688 for HEAT.
The company also reported that, “Data from six GSK studies with 2,595 patients show higher viral load reduction (94% and above in patients with viral load 100,000 copies at 24 weeks) than was seen in the ACTG study.” Although 24 weeks is early data and the studies are being lumped together without regard for other considerations, the participants in 5202 had not all reached that point.
GSK also pointed to the fact that the study did not require testing for hypersensitivity to the Ziagen medication contained in Epzicom. Malaise is one of the symptoms of this potentially dangerous allergic-like reaction. Moreover, a company representative said that under ACTG 5202’s strict intent-to-treat analysis, anyone who was started on Epzicom but switched to Truvada and failed to do well would be counted as a failure for Epzicom.
Regardless of how everything shakes out, not all people can take Truvada, or Viread, one of its components. For example, it is not recommended for people with kidney problems because of its potential for renal toxicity. Further results from 5202 (the next analysis is due in June) are now eagerly awaited. As Positively Aware went to press, the DHHS panel recommended no changes to the guidelines at this time (see above).
back to top
Lactobacillus for a healthy vagina
It looks like once again, Lactobacillus does a vagina good.
Researchers found that when HIV-positive women had increased levels of the naturally occurring vaginal bacteria, their genital HIV decreased, and vice versa. The study, presented at CROI in February looked at naturally occurring levels of hydrogen peroxide-producing (H2O2+) Lactobacillus in 57 women in Seattle and Rochester, New York.
Women who acquired H2O2+ Lactobacillus had a drop in genital HIV while those who lost it had an increase (-.7 vs. +.5 log). The changes were statistically significant, although HIV was found in only 17% of samples to begin with.
The research group expected these results. They report in their abstract that, “[H2O2+] Lactobacillus is a key regulator of the vaginal ecosystem and may decrease HIV-1 replication through direct efforts as well as by suppression of pathogenic bacteria.”
HIV-positive women have taken offense at health efforts that seem solely important for lowering their risk of transmission to others. Positively Aware asked lead researcher Jane Hitti, M.D., of the University of Washington about this and whether less vaginal viral load was a good thing in itself. Hitti responded, “Yes, absolutely it’s a good thing.” It helps, for example, in fighting bacterial vaginosis, another sexually transmitted disease. It also did no damage to the other good bacteria found in the vagina.
back to top
Chewing infant’s food can lead to HIV
Also at CROI, the CDC reported on three cases where HIV-positive women who pre-chewed food for infants transmitted the virus this way. According to a CDC press release, “A thorough investigation of three cases of pediatric HIV infection in two U.S. cities between 1993 and 2004 indicates that pre-masticated (pre-chewed) food can be a source of HIV transmission if infected blood is present in the saliva. Researchers attribute the HIV transmission in these cases to the children’s ingestion of HIV-infected blood—not saliva—present in the pre-masticated food.”
The researchers were able to rule out other possible causes of transmission such as breastfeeding, sexual abuse, and needle stick injury, and believe that blood from bleeding gums caused the infections. The blood then entered the child’s bloodstream through a cut, sore, or inflammation of the mouth or digestive tract. According to the CDC, these conditions are common during teething and some childhood diseases such as inflamed tonsils. The CDC outlined the three infections as follows:
“Case 1 (Memphis): African-American girl diagnosed in 2004 at the age of 9 months. The infant had previously tested negative for HIV three times (at 41, 60, and 118 days). The mother is HIV-positive and reported providing pre-masticated food to the child, beginning when the girl was 4 months old. The child is currently receiving HIV care.
“Case 2 (Miami): African-American male diagnosed in 1995 at the age of 39 months. The child previously tested negative for HIV twice (at 20 and 21 months). The infant’s mother had AIDS and reported providing pre-masticated food to the child, though she could not specify the time frame. The child died of AIDS in 1996.
“Case 3 (Miami): African-American boy diagnosed in 1993 at the age of 15 months. The infant’s mother is HIV-negative. However, the child’s HIV-positive great-aunt served as a caregiver and provided pre-masticated food to the infant when he was between the ages of 9 and 14 months. The child’s mother did not know that the aunt was HIV-positive until the aunt’s death due to AIDS in 1993. The boy is currently receiving HIV care.
“In the course of the investigation, researchers found that HIV-infected caregivers in Cases 1 and 3 reported bleeding gums and/or mouth sores during the time that they were providing pre-masticating food for the infants; the details of Case 2’s oral health at the time of pre-mastication are unknown. Further genetic analysis of the children’s specific HIV strains indicated that the caregivers who pre-masticated the food were the sources of transmission in Cases 1 and 2. Although Case 3’s caregiver died before a blood sample could be obtained, there was no match between the caregiver’s HIV-infected male partner and the child’s HIV strains.”
back to top
Swiss experts say people with undetectable viral load and no STI cannot transmit HIV during sex
(The following is taken from the National AIDS Map, in London. Visit www.aidsmap.org for the full report.) Swiss HIV experts have produced the first-ever consensus statement to say that HIV-positive individuals on effective antiretroviral therapy and without sexually transmitted infections (STIs) are sexually non-infectious. The statement is published in this week’s [January 30, 2008] Bulletin of Swiss Medicine (Bulletin des médecins suisses). The statement also discusses the implications for doctors, HIV-positive people, prevention, and the legal system. The statement, on behalf of the Swiss Federal Commission for HIV/AIDS, was authored by four of Switzerland’s foremost HIV experts… . The statement’s headline statement says that “after review of the medical literature and extensive discussion,” the Swiss Federal Commission for HIV/AIDS resolves that, “An HIV-infected person on antiretroviral therapy with completely suppressed viraemia (“effective ART”) is not sexually infectious, i.e. cannot transmit HIV through sexual contact.” It goes on to say that this statement is valid as long as:
- the person adheres to antiretroviral therapy, the effects of which must be evaluated regularly by the treating physician, and
- the viral load has been suppressed (less than 40 copies/ml) for at least six months, and
- there are no other sexually transmitted infections.
The article begins by stating that the Commission “realizes that medical and biologic data available today do not permit proof that HIV-infection during effective antiretroviral therapy is impossible, because the non-occurrence of an improbable event cannot be proven. If no transmission events were observed among 100 couples followed for two years, for instance, there might still be some such events if 10,000 couples are followed for 10 years. The situation is analogous to 1986, when the statement ‘HIV cannot be transmitted by kissing’ was publicized. This statement has not been proven, but after 20 years’ experience its accuracy appears highly plausible.” [Editor’s note: There has been at least one documented U.S. case of HIV transmitted via deep kissing when the infected person had oral disease and blood present in his mouth.]
back to top
|
