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BETA News Briefs

By Liz Highleyman

Autumn, 2000


Lopinavir Wins FDA Approval

On September 15, the U.S. Food and Drug Administration (FDA) approved Abbott Laboratories' new protease inhibitor (PI) lopinavir. Kaletra, formerly ABT-378/r, is a combination of lopinavir plus a small amount of ritonavir (Norvir), which helps boost lopinavir blood levels. Study results presented by Abbott showed that lopinavir reduced HIV viral load to undetectable levels in slightly over 80% of persons who used the drug for nearly two years. The earlier-than-expected approval was granted despite FDA official Heidi Jolson's caution that the drug's benefits were "still a little theoretical." Reported side effects of lopinavir include high cholesterol and triglyceride levels and pancreatitis (inflammation of the pancreas). About 1% of those taking the drug developed pancreatitis; people taking lopinavir should have their blood amylase levels (a marker for pancreatitis) monitored regularly.


New Abacavir Hypersensitivity Warning

Abacavir (Ziagen), a nucleoside analog drug, is known to cause a potentially life-threatening hypersensitivity reaction in about 5% of people. These reactions had previously been seen when restarting the drug after it was interrupted in people who had already experienced hypersensitivity symptoms. The symptoms of hypersensitivity include malaise, fever, nausea, shortness or breath, sore throat, and skin rashes. In July, Glaxo Wellcome reported that a severe, potentially fatal reaction could develop within hours after restarting the drug even in people who had not previously experienced any symptoms of abacavir hypersensitivity. The company issued a "Dear Health Care Provider" letter and added a "black box" (emphasized) warning to abacavir packages. Glaxo recommends that providers who contemplate reintroducing abacavir after an interruption should evaluate the patient for any possible past symptoms of a hypersensitivity reaction, and should not restart the drug if any such symptoms are found. In addition, providers should use caution in reintroducing the drug even in persons who have not previously shown any hypersensitivity symptoms; such people should be monitored and have access to emergency medical care. Although most persons who have experienced a reaction have developed symptoms within hours, others have developed severe symptoms after days or weeks. Abacavir is also a component of Trizivir (AZT[Retrovir]/3TC[Epivir]/abacavir).


Twice-Daily ddI Recommended

In August, Bristol-Meyers Squibb issued a letter to health-care providers recommending that its nucleoside analog drug ddI (Videx) be taken twice rather than once a day. The recommendation came after a recent study of combination regimens in over 750 persons indicated, according to the company, that "a twice-a-day dosing regimen for Videx was superior to once-a-day dosage." Over a period of 48 weeks, people taking ddI twice daily had a greater reduction in HIV viral load than those taking the drug once daily. Once-daily ddI should only be included in a regimen if a person cannot tolerate twice-daily dosing.


Medical Marijuana Does Not Increase HIV Viral Load

At the XIII International AIDS Conference in Durban, South Africa, this past July, Donald Abrams, MD, and colleagues from the University of California, San Francisco presented study results showing that marijuana (cannabis) does not affect HIV viral loads in persons taking PIs. The study was conducted to determine whether marijuana interacts with PIs, which are metabolized by the same liver enzyme system as cannabis. Medicinal marijuana is used by people with HIV to control wasting and to relieve nausea associated with anti-HIV therapy.

Study participants either smoked marijuana, took oral dronabinol (Marinol) THC pills, or took placebo pills. There were no significant differences in HIV viral load among the groups over the course of the 21-day study; HIV RNA levels decreased in all study arms, but more so in those using smoked marijuana or oral dronabinol. In addition, the study showed that the participants using smoked marijuana or oral dronabinol achieved a significantly higher caloric intake and a greater weight gain. The study was the first to look at the effects of medical marijuana in people with HIV.

Dr. Abrams' findings appear amidst the backdrop of a Supreme Court ruling in late August against California clubs that provide medical marijuana. The court's decision came in response to a federal appeal of a 9th Circuit Court ruling that would have allowed clubs to provide medicinal cannabis pursuant to California's Proposition 215, passed by voters in November 1996. Although district court judge Charles Breyer ruled that the government had failed to demonstrate why seriously ill patients should not have access to medical marijuana, the Supreme Court decision blocked cannabis distribution while the federal appeal is underway.


HIV Can Travel in B-Cells

New research from the National Institute of Allergy and Infectious Diseases (NIAID) demonstrates that HIV can attach to B-cells and thus spread throughout the body. B-cells are a type of immune system white blood cell. It has long been known that HIV enters and destroys T-cells, another type of immune cell. B-cells and T-cells work together to coordinate the body's immune response. The latest research shows that HIV can attach to B-cell surfaces using the CD21 receptor, which is involved in triggering antibody production. B-cell-bound HIV was found in blood and lymphoid tissue samples from 23 HIV-infected people. According to researcher Susan Moir, "HIV does not appear to reproduce inside B-cells" -- as it does in T-cells -- "but rather hitches a ride on the [B-] cell surface so it is free to jump to nearby T-cells." NIAID director Anthony Fauci, MD, said the results may help explain how HIV infection can persist. Dr. Fauci said, "Identifying this pool of HIV-carrying cells opens new avenues for treating the infection." A similar mechanism may occur with follicular dendritic cells, tissue cells that also carry the CD21 receptor. The research was reported in the September 5 issue of the Journal of Experimental Medicine.


Opportunistic Infection (OI) News

Although rates of most OIs have fallen among HIV-infected people who take combination antiretroviral regimens, they remain a concern for many. In July, the FDA approved the antifungal drug AmBisome for the treatment of cryptococcal meningitis, a life-threatening brain and spinal cord infection, in persons with HIV. AmBisome is a liposomal formulation of amphotericin B developed by Gilead Sciences and Fujisawa. By encapsulating amphotericin B in a lipid bubble, it can be more precisely targeted to the infected cells and causes fewer of the severe side effects (e.g., kidney toxicity and fever) associated with the drug.

In June, researchers from the U.S. Centers for Disease Control and Prevention (CDC) reported that Pneumocystis carinii, the agent that causes PCP pneumonia, appears to be developing resistance to sulfone and sulfonamide antibiotic drugs. A study of P. carinii samples obtained in five U.S. cities between 1995-1998 showed that mutations that could potentially confer resistance were present in up to 50% of isolates.


Drugs Reduce Viral Load -- But Not to Safe Levels

According to research reported in the August 15 issue of the Annals of Internal Medicine, about one-third of HIV-positive men continue to shed (release or discharge) HIV in their semen even after six months of antiretroviral therapy. While anti-HIV treatment reduces seminal viral loads, they remain high enough to allow transmission of the virus. Paulo Barroso, MD, and colleagues from the Federal University in Rio de Janeiro, Brazil, studied 93 HIV-infected men taking either two-drug or three-drug antiviral regimens. After six months, 33% of the men still had HIV in their semen, compared with 74% before treatment; HIV viral load was detectable in the blood of 96% of the men before treatment and 38% of the men after treatment. Interestingly, similar HIV viral load rates were found in the cervical/vaginal fluids of HIV-infected women in a recent French study. Laurent Belec, MD, and colleagues from the Georges Pompidou Hospital in Paris found HIV RNA in the genital fluid of 39% of 54 women studied; the prevalence of HIV was inversely related to the number of anti-HIV drugs taken. The research was reported in the July issue of the Journal of Infectious Diseases.

Although HIV treatment may be credited with a reduction in sexual transmission of HIV, it is not likely to eliminate transmission, and thus safer sex measures such as using condoms are still recommended.


Nonoxynol-9 (N-9) Not Effective in Reducing HIV Transmission

In August, Helene Gayle, MD, director of the CDC's National Center for HIV, STD, and TB Prevention, issued a "Dear Colleague" letter warning that N-9 is ineffective in preventing HIV transmission and may in fact increase the risk of transmission. N-9, a spermicide and microbicide, is an ingredient in many contraceptive gels and foams, and in lubricants on some types of condoms. Studies have shown that N-9 can irritate and damage mucous membranes in the vagina and rectum, especially with frequent use. A report presented at the Durban AIDS conference indicated that use of Advantage S, a microbicide containing N-9, was associated with an increased risk of HIV infection in a study of nearly 1,000 female sex workers in Africa and Thailand; rates of HIV infection were almost twice as high in the women who used N-9. According to Dr. Gayle's letter, "N-9 has now been proven ineffective against HIV transmission . . . The possibility of risk, with no benefit, indicates that N-9 should not be recommended as an effective means of HIV prevention . . . Anyone currently using N-9 as a microbicide to protect themselves from HIV transmission during anal intercourse should be informed of the ineffectiveness of this agent and warned of the potential risk of this practice." However, the CDC recommends that using a condom lubricated with N-9 is better than not using a condom at all.


Boiling Breast Milk Can Reduce Vertical Transmission

Several recent news items concern vertical (also known as perinatal) transmission of HIV from mothers to their infants before, during, or shortly after birth. First, a study published in the July issue of the Pediatric Infectious Disease Journal showed that rates of vertical transmission have declined in the U.S., from 20.7% between 1985-1990 to 6.5% between 1990-1997. The authors attributed much of the decline to the routine use of AZT by pregnant women.

A report published in the October 5 issue of the New England Journal of Medicine showed that a shorter course of AZT therapy for newborns may work as well as more prolonged treatment. The currently recommended standard perinatal transmission prevention regimen involves treating women with AZT starting at the 28th week of pregnancy, and treating their infants for six weeks after birth. Researchers from the Harvard School of Public Health studied 1,500 pregnant Thai women. Some of the women received the standard AZT treatment starting at the 28th week of pregnancy while others received a shorter course starting at the 25th week. Among the infants, some received AZT for the standard six weeks, while others took AZT for just three days. Women who received the shorter course of AZT had a significantly higher chance of transmitting AZT to their babies that those who received the standard regimen. However, infants who received the three-day AZT regimen were no more likely to contract HIV than those who took AZT for six weeks. The researchers concluded that women should continue to receive AZT starting at the 28th week of pregnancy, but that newborns only need to take AZT for three days. The shorter, less costly infant AZT regimen may be especially beneficial for developing countries that have few resources to devote to health care.

In related news, the South African Medical Research Council announced in early October that boiling breast milk can help prevent the transmission of HIV from a pregnant woman to her child. The group reported in its annual report that HIV is killed when breast milk is heated to 56-63° C (132.8-145.4° F) for twenty minutes; heating to this temperature preserves 80% of the nutrients and antibodies found in the milk.


Study Debunks Polio Vaccine as Cause of AIDS

Study results released in September appear to confirm that AIDS did not originate from contaminated polio vaccines tested in Africa in the 1950s. Claudio Basilico, MD, and colleagues from an advisory committee convened by the Wistar Institute in Philadelphia, which developed the vaccine, announced at a Royal Society of London meeting that they found "no evidence to support the hypothesis of the polio vaccine origin of AIDS." Tests of seven samples of the original oral polio vaccine did not show any evidence of chimpanzee genes or of HIV or simian immunodeficiency virus (SIV, a monkey virus related to HIV). Basilico said the vaccine could not be completely ruled out as a factor in the introduction of HIV into the human population, due to incomplete record keeping, but he did say the study "makes it more unlikely." The primary proponent of the polio vaccine theory is former BBC journalist Edward Hooper, who promotes it in his book The River: A Journey to the Source of HIV and AIDS. Hooper contends that chimpanzee tissue was used to develop the polio vaccine, a claim denied by Wistar officials. Despite the new evidence, Hooper continues to defend his theory.


AIDS No Longer Among Top 15 Causes of Death in U.S.

According to a report released by the CDC's National Center for Health Statistics in July, HIV/AIDS is no longer among the 15 leading causes of death in the U.S. The report was based on data collected through 1998. The decline in HIV-related deaths was attributed to combination anti-retroviral therapy, which is credited with delayed AIDS deaths. The top three leading causes of death for all Americans were heart disease, cancer, and strokes. However, HIV/AIDS remains the leading cause of death for African-American men and women between the ages of 25 and 44.


New Ryan White CARE Funding, More World Bank Loans for AIDS

On October 5, Congress unanimously voted to continue Ryan White CARE Act funding, providing more than $1 billion for HIV/AIDS prevention and treatment. The reauthorized legislation is a compromise between two formulas that would have allocated funding differently on the basis of HIV infections versus cumulative AIDS cases. In past years, Ryan White funding was based on AIDS cases alone, not HIV infections. Cities such as San Francisco, which has experienced a large number of AIDS cases since early in the epidemic, favored a version that would have maintained its funding at minimally reduced levels. Areas that have had fewer cumulative cases of AIDS preferred a formula that would have cut up to 25% of the funding from the previous cities and allocated more to areas that have seen proportionately greater increases in HIV infections in recent years. The compromise legislation will cut San Francisco's funding by 15% over five years. Supporters of the new formula, which will go into effect in 2005, say it will direct more money to "the new face of AIDS": women, infants, minority and rural populations, and those living in the southeast region of the U.S. Opponents say that the new formula will allocate less money to gay men, who continue to be heavily impacted by HIV/AIDS. The reauthorized legislation includes $20 million for prevention of vertical transmission and $30 million for partner notification programs.

In other funding news, President Clinton in August signed legislation that will provide over $400 million to fight AIDS and other infectious diseases in Africa. The move comes after the government declared AIDS a "national emergency" this past spring. The legislation includes $300 million for education, testing, and prevention of perinatal transmission; $60 million for vaccine programs; and $60 million for tuberculosis prevention and treatment. In announcing the legislation, Clinton said, "AIDS threatens the economies of the poorest countries, the stability of friendly nations, and the future of fragile democracies." The legislation will also create a World Bank trust fund.

The World Bank, which has been under increasing fire from protesters over the past year, announced in September that it is beginning a campaign to fight AIDS in Africa. The bank is expected to provide $500 million in emergency low-interest loans for AIDS prevention and treatment programs for the poorest countries. The cheap loans would not be available to less poor but still needy countries such as South Africa. World Bank critics contend that loans merely increase the debt burden of poor countries, and that loan forgiveness and outright grants are the best ways to promote improved health care in the developing world.


Liz Highleyman is a freelance medical writer.


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