Published in the Bulletin of Experimental Treatments for AIDS September 1997 issue, by the San Francisco AIDS Foundation.

September 1997 Table of Contents

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News Briefs

By Liz Highleyman

In This Issue

The use of combination antiretroviral therapy including protease inhibitors presents a variety of challenges. This issue features articles about protease inhibitor drug interactions, drug failure and adherence to complex drug regimens. Other articles discuss anal neoplasia, progressive multifocal leukoencephalopathy and Chinese medicine for women with HIV disease.

1592 Compassionate Use Program

Glaxo Wellcome this summer announced a new compassionate use program for its experimental nucleoside analog drug 1592 (also known as abacavir). The program is the result of extensive effort by AIDS treatment advocates. The program will enroll 2,400 adults by the end of 1997; activists had sought a much larger enrollment. Eligible patients must have fewer than 100 CD4 T-cells/mm3, a viral load greater than 30,000 copies/mL, and have had prior treatment with 2 nucleoside analogs or intolerance to a previous combination regimen. An expanded access program for 250 children is also enrolling. Interested persons can ask their physician to call 800-501-4672 for additional information and registration.

PEP Program Begins in San Francisco

In early October the San Francisco Department of Public Health (DPH) will begin providing postexposure prophylaxis (PEP) to persons who have been exposed to HIV. PEP is the administration of a 28-day regimen of 2- or 3-drug combination therapy beginning within 72 hours after potential exposure (see BETA, June 1997, page 46). The goal of PEP is to prevent HIV from gaining a foothold in the body. The DPH PEP project—the first in the nation—will provide PEP to 500 HIV-exposed individuals as part of a research study, and will continue providing PEP to others after study enrollment is completed. Researchers hope to gain information about the feasibility and ramifications of a larger PEP program. PEP will be available at San Francisco General Hospital and at the city STD clinic. For information and eligibility requirements, call the California AIDS Hotline at 800-FOR-AIDS.

Triple Anti-HIV Therapy Reduces Disease Progression and Deaths

Recent study results show that the triple drug combination of saquinavir (Invirase), AZT (Retrovir) and ddC (Hivid) reduces HIV disease progression and death by 50%. The study was the largest HIV/AIDS trial ever conducted, involving over 3,400 participants in 22 countries. The participants, who had no or minimal previous antiretroviral treatment, were followed for 17 months. Those taking the triple combination experienced 76 endpoints (first AIDS-defining illnesses or deaths) compared to 142 endpoints in the AZT/ddC arm and 116 endpoints in the AZT/saquinavir arm. This is the first study to show a clinical benefit in treatment-naive persons using combination therapy containing a protease inhibitor.

Combination Therapy for Children with HIV

The National Institutes of Allergy and Infectious Diseases (NIAID) stopped a study of antiretroviral therapy in children (ACTG 300) in June after it was shown that combination ther-apy with AZT plus 3TC (Epivir) reduced risk of HIV disease progression by 70% and risk of death by 80% compared to ddI (Videx) alone. The study included 615 children (42 days to 15 years old) at 87 U.S. medical centers who had symptomatic HIV disease and little or no prior antiretroviral therapy.

USPHS Recommendations for HIV Treatment During Pregnancy

In early August the U.S. Public Health Service (USPHS) issued draft recommendations for the use of anti-HIV therapy during pregnancy. USPHS guidelines issued in February 1994 recommended AZT for pregnant HIV positive women after the ACTG 076 study showed that the drug dramatically reduced perinatal HIV transmission. The updated recommendations recognize the importance of both optimal treatment for pregnant women and reduction of the risk of HIV transmission to infants, and state that “guidelines for optimal antiretroviral therapy in pregnant HIV-infected women should be the same as those delineated for non-pregnant adults.” Recently released federal guidelines recommend combination regimens that include a protease inhibitor. To prevent perinatal transmission, AZT should be included in a regimen for HIV positive women; however, AZT monotherapy is considered suboptimal. The panel acknowledged that the long-term effects of anti-HIV therapy on fetuses and infants are unknown and recommended further study.

Tuberculosis Prophylaxis Unnecessary for Many People with HIV

New findings suggest that preventive treatment for tuberculosis (TB) is not necessary for people with HIV who have anergy (negative TB skin test results due to poor immune response). A study conducted by the Terry Beirn Community Programs for Clinical Research on AIDS (reported in the July 31, 1997 issue of The New England Journal of Medicine) compared 2 groups of HIV positive individuals at high risk for TB; high-risk individuals include homeless persons and injection drug users. One group received preventive therapy with the anti-TB drug isoniazid, while the other group received placebo. The number of persons developing active TB disease did not differ significantly between the 2 groups (for more details, see Research Notes, page 54). According to Anthony Fauci, MD, of NIAID, “this study suggests we can make more effective use of TB prevention resources by focusing on HIV-infected persons with known TB infections or who have close contact with another individual with active TB.”

For those HIV positive persons who have been exposed to Mycobacterium tuberculosis, new research from Spain published in the August 11, 1997 Archives of Internal Medicine indicates that long-term (12 month) isoniazid prophylaxis is effective in preventing active TB disease and leads to increased survival in people with HIV.

IAS-USA Publishes Updated Guidelines

Shortly after the mid-June release of the Department of Health and Human Services’ guidelines for the use of anti-HIV therapy, the International AIDS Society-USA published its own antiretroviral therapy guidelines in the June 25, 1997 issue of The Journal of the American Medical Association. The new guidelines—which recommend viral load testing and early initiation of aggressive antiretroviral therapy for those who choose treatment—are an updated version of guidelines released by the group at the XI International Conference on AIDS in July 1996.

CMV Intraocular Implant Effective

Results from a study conducted by the Ganciclovir Implant Study Group and reported in the July 10, 1997 issue of The New England Journal of Medicine show that sustained-release ganciclovir eye implants can delay progression of cytomegalovirus (CMV) retinitis in people with AIDS. Untreated CMV disease can result in blindness and death.

Study participants received either a ganciclovir implant—a device inserted into the eye that releases a steady amount of the drug—or intravenous ganciclovir. People who received the implant experienced progression of retinitis in an average of 221 days, compared to 71 days for people who received intravenous ganciclovir. However, those who received the implant were more likely to experience CMV disease in the untreated eye or in other parts of the body.

New HIV Co-Receptor Findings

Researchers at the National Cancer Institute reported in the August 15, 1997 issue of Science that they had found a genetic mutation of the chemokine receptor CCR2 that appears to slow AIDS progression. Normal CCR2, which is found on the surface of certain human cells, acts as an HIV co-receptor with CD4, allowing the virus to enter cells. The newly discovered mutation, which is estimated to occur in 20-25% of Americans of European and African descent, was shown to slow progression of HIV/AIDS by up to 4 years.

Individuals who have a genetic mutation of the CCR5 co-receptor also experience slower disease progression. Nearly 30% of long-term nonprogressors who have lived 16 years or more with HIV have either the CCR2 or the CCR5 mutation. Despite earlier speculation, however, neither mutation provides absolute protection from HIV infection (see BETA, June 1997).

In related news, 2 new co-receptors—named Bonzo and BOB (Brother of Bonzo)—were recently discovered by researchers at the New York University Howard Hughes Medical Institute. The findings were reported in the June 17, 1997 issue of Nature. A second group also reported the discovery of the Bonzo co-receptor, which they call STRL33. Both HIV and the simian immunodeficiency virus (SIV) can use the new co-receptors along with CD4 to enter cells.

Unusual HIV Strains Found in U.S.

Officials with the Maryland Department of Health and Mental Hygiene reported in July that they had found people infected with 2 unusual strains of HIV. One individual represents the first U.S. case of infection with HIV group M, subtype G. The other was the second reported U.S. case of infection with a group O strain of HIV. Several hundred cases of the unusual strains have been reported worldwide, primarily in Central and West Africa. The 2 individuals in Maryland contracted HIV through unprotected heterosexual sex while in Africa. Most people with HIV in the U.S. are infected with the group M, subtype B strain. Health officials stated that the 2 rare strains could be detected using standard ELISA and Western Blot HIV antibody tests.

STD Treatment Reduces Semen Viral Load

New research reinforces the link between HIV disease and other sexually transmitted diseases (STD). Researchers from the University of North Carolina School of Medicine reported in the June 28, 1997 issue of The Lancet that HIV positive men who also had urethritis had 8 times as much HIV in their semen as men without urethritis. Urethritis, or inflammation of the urethra, is a symptom of STD such as gonorrhea and chlamydiasis. The study included 135 men in Malawi, a country with high rates of STD and HIV. After 2 weeks of antibiotic treatment, levels of HIV RNA in the semen of the co-infected men fell to levels similar to those seen in men who did not have an STD; HIV RNA blood levels did not change. Experts are hopeful that STD treatment may help curb HIV transmission.

Home HIV Test Taken Off Market

The Confide brand home HIV test, manufactured by Direct Access Diagnostics, was taken off the market this past summer due to lack of demand and low sales. The company has stopped shipping the test and has asked retailers to remove existing stocks. The Home Access home HIV test system remains on the market.

AmBisome Approved for Fungal Infections

The Antiviral Drug Products Advisory Committee of the Food and Drug Administration (FDA) voted unanimously to recommend the approval of liposomal amphotericin B, marketed as AmBisome, for the treatment of fevers of unknown origin in people with low numbers of neutrophils, a type of white blood cell that defends against invading organisms such as fungi. The drug amphotericin B is effective against fungal infections, but is associated with severe side effects. AmBisome is a formulation of amphotericin B encased in fat bubbles called liposomes, which gives it a lower toxicity.

Kemron Trial Stopped

In June the National Institutes of Health ended a study of low-dose oral alpha interferon, also known as Kemron. The low-dose oral formulation of the cytokine—which some, especially within African American communities, have promoted as a treatment for AIDS—had not been shown effective in previous clinical trials. The current study was terminated due to lack of participants and a high drop-out rate, as well as a changing treat-ment environment due to the advent of protease inhibitor drugs. Intravenous alpha interferon is used to treat hepatitis B and re-mains under study as an immunomodulatory treatment for AIDS.

Delavirdine and DaunoXome Added to ADAP

Delavirdine (Rescriptor), a new non-nucleoside reverse transcriptase inhibitor (NNRTI) drug which was FDA-approved in April, was added to the California AIDS Drug Assistance Program (ADAP) formulary on July 18, 1997. With this addition, all FDA-approved anti-HIV drugs are covered under the state program.

DaunoXome, a liposomal formulation of daunorubicin, was also added to the ADAP formulary. The drug is used to treat Kaposi’s sarcoma and other cancers.

U.S. AIDS Death Rate Decreases

On July 14, 1997, the Centers for Disease Control and Prevention (CDC) reported that deaths due to AIDS in the U.S. decreased by 19% in the first 3 quarters of 1996, compared to the corresponding period in 1995. The number of deaths fell from 37,900 to 30,700. The new data confirm and extend the downward trend noted earlier this year, when the CDC reported a 13% decrease in AIDS deaths in the first half of 1996. As was the case with the earlier 6-month figures, the decrease was greatest among whites, who experienced a death rate decline of 28%. For Latinos the decrease was 16%, and for African Americans the decline was 10%. In contrast to earlier figures which showed a 3% increase in deaths due to AIDS among women in the first half of 1996, the 9-month figures show a decline of 7%, the first ever decrease in this group. Experts attributed the decrease in AIDS deaths to new drug therapies and greater access to health care.

New Global AIDS Figures

The World Health Organization (WHO) released new global HIV/AIDS numbers in early July. WHO said that as of June 30, 1997 a total of 1,644,183 cumulative cases of AIDS had been officially counted, based on reports from health ministries in 191 member countries. This number reflects an increase in AIDS incidence of 18% this year, compared to a 19% increase in the year ending June 30, 1996. The number of AIDS cases was highest in the U.S. (581,429 cases), followed by Brazil (103,262), Tanzania (82,174) and Thailand (59,782). The agency believes the official numbers are far below the actual number of AIDS cases, largely due to incomplete reporting.

Liz Highleyman is Assistant Editor of BETA.

Page last updated 1 October 1997

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