Important note: Information you find here was accurate in 1999. The state of the art may have changed since the publication date.
BETA is published four times a year by the San Francisco AIDS Foundataion.
On behalf of the entire BETA staff and the San Francisco AIDS Foundation, I am pleased to present this special edition. While we are calling it the "1999 Year-End Special Edition," this expanded issue was prepared with the conclusion of not only the year and the millennium in mind, but also the first 20 years of the HIV/AIDS pandemic.
Treatment of HIV infection has become increasingly complicated. Once limited in therapeutic options, clinicians now can choose from 14 different approved antiretrovirals and numerous other agents in clinical trials. Highly active antiretroviral therapy (HAART) today may be a "protease-sparing" regimen built on a foundation of powerful new non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs).
Hepatitis C is a liver disease caused by a virus. The majority of people infected with the hepatitis C virus (HCV) develop chronic hepatitis, which may lead to fibrosis and cirrhosis (scarring) of the liver, liver cancer, and ultimately fatal liver failure. Although the rate of new hepatitis C infections has declined in the past decade, nearly four million Americans are believed to be infected, and many will likely develop liver damage as the effects of this slowly progressing disease become apparent.
Adolescents constitute one of the most invisible populations affected by HIV disease in the U.S. The difficulty categorizing adolescents into pediatric or adult systems of care, the lack of access of many teenagers to medical services, and the fact that the young people most likely to become HIV-infected are often those who are the most disenfranchised are but a few reasons.
Despite the fact that HIV transmission is preventable, the HIV/AIDS epidemic continues to spread. This past May, the World Health Organization (WHO) declared AIDS to be the world's deadliest infectious disease, and the fourth most frequent cause of death overall.
Experts believe that subunit vaccines may best be used as part of a "prime-boost" combination vaccine strategy. A vaccine such as a powerful avian pox vector would serve as the "prime" by sparking an adequate CTL response; soluble HIV proteins (the "boost") would then be used to stimulate neutralizing antibodies.
Trial protocols are available at the AIDS Clinical Trials Information Service (ACTIS). Call 800-TRIALS-A, or visit the ACTIS Web site at http://www.actis.org.
Various dermatological conditions have been associated with HIV disease since the beginning of the AIDS epidemic. The purple lesions characteristic of Kaposi's sarcoma (KS) became a symbol for this modern plague. Other skin complications-such as herpes zoster (shingles), herpes simplex, and molluscum contagiosum-were so common that they sometimes were regarded as informal markers of immune deficiency.
HIV Rebounds When Treatment Stops; Drug-Resistant HIV More Common; Early Access Program for ABT-378/r; FDA Panel Fails to Recommend Adefovir Approval; Lodenosine Trials Stopped Due to Safety Concerns; Recreational Drugs and Protease Inhibitors. . . .
Data from several studies involving emivirine (Coactinon) were presented at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), held September 26-29, 1999, in San Francisco.
This review article discusses selected major medical issues related to HIV positive women's health in the context of the year-and era-drawing to an end. To the extent that the goal is the provision of a broad perspective on trends and developments, an overview of both recent and historically significant data is provided.
At the end of 1999, UNAIDS/WHO estimates that 12.2 million women and 10.1 million men age 15-49 were living with HIV in sub-Saharan Africa, as were 11 million orphans
Kathryn Anastos, MD, proposed distinct timepoints for viral load testing to optimize the information such tests provide: at serodiagnosis, to drive decisions about initial antiretroviral therapy
"Western leaders must reaffirm their commitment to 'bridging the gap,' the theme of the last World AIDS Conference, by investing in developing countries, especially Africa &In the scientific arena we tend to get excited by new discoveries and forget to build on what we have already discovered. But we must implement these discoveries.
This edition of “Conference Coverage” summarizes findings from several important HIV-related conferences convened in 1999, including the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), held September 26-29 in San Francisco.
At the 39th ICAAC, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), described an experimental trial whereby successful HAART was discontinued. Dr. Fauci's plenary presentation was entitled "Host Factors in the Pathogenesis of HIV Disease."
Charles A.B. Boucher, MD, from the University Hospital in Utrecht, The Netherlands, has proposed an algorithm regarding usage of new, experimental drug resistance tests.
A new anti-HIV "entry inhibitor" drug called PRO 542 (Progenics Pharmaceuticals) has been well tolerated and shows anti-HIV benefits in phase I studies. Expanded phase II testing will be pursued, according to J. Jacobson, MD, from Mount Sinai Medical Center in New York City.
The most impressive anti-HIV drug trial results at the 39th ICAAC were presented during the late-breaker session. Thirty-six-week interim results of the potent double PI combination of ABT-378 plus ritonavir (ABT-378/r) were reported by Joseph Eron, MD, from the University of North Carolina at Chapel Hill.
A few abstracts at the 39th ICAAC addressed the issue of BFR. Since PIs were the first drugs to be linked with fat redistribution, some researchers wanted to determine whether viral load would increase if a PI was changed to an NNRTI. A second endpoint would be the potential effects on fat redistribution.
Genital warts increase HIV viral load in semen. In a study presented at the 39th ICAAC by P.F. Barroso, MD, and colleagues from Johns Hopkins University in Baltimore, people with genital warts had a significantly higher semen viral load than those without genital warts.
Kaposi's sarcoma herpesvirus (KSHV) is transmitted by deep oral "French" kissing. This study was presented at the 39th ICAAC by J. Pauk, MD, and colleagues from the University of Washington in Seattle. One hundred men who have sex with men (79% HIV negative) were recruited for the study.
All listings are taken from Trials Search, an online database of open clinical trials for HIV-infected individuals. Trials Search, a comprehensive source for clinical trial information, is available at http://hivinsite.ucsf.edu/tsearch.
This issue of BETA features articles on a broad range of current topics, including resistance testing ("Genotypic and Phenotypic Resistance Testing"), global reports on nutrition and HIV infection ("Nutrition and HIV Infection") and the perspectives on HIV of Jay A. Levy, MD, the preeminent virologist and HIV researcher.
Nearly 20 years after he emerged as a preeminent HIV researcher, Jay A. Levy, MD, took some time to speak with BETA and to reflect on the current state of HIV/AIDS research and his experiences. The following article presents a world-renowned researcher's more philosophical, overarching perspectives on the HIV/AIDS epidemic. (See the sidebar for a biographical profile of Dr. Levy.)
Jay A. Levy, MD, an AIDS and cancer researcher and educator at the University of California at San Francisco (UCSF) School of Medicine, is Professor in the Department of Medicine and Research Associate in the Cancer Research Institute. He is head of the Laboratory of Tumor and AIDS Virus Research at UCSF.
The advent of protease inhibitors in 1996 and the widespread use of highly active antiretroviral therapy (HAART) in the ensuing years has had a dramatic effect on HIV disease progression and rates of death due to AIDS. But many people also wonder whether HAART affects HIV transmission.
Sexual activities fall along a continuum of risk. Unprotected anal sex carries the highest risk of infection, followed by unprotected vaginal sex. Oral sex on a man or a woman carries a much lower risk.
The power of highly active antiretroviral therapy (HAART) to suppress HIV has revolutionized the clinical management of HIV disease in the developed world. The capacity for HIV to develop resistance to antiretroviral drugs, however, is a significant cause of the failure of HAART.
Mutations Associated with Resistance to HIV Protease Inhibitors; Mutations Associated with Resistance to Nucleoside and Nucleotide HIV Reverse Transcriptase Inhibitors; Mutations Associated with Resistance to Non-Nucleoside HIV Reverse Transcriptase Inhibitors
The Third International Conference on Nutrition and HIV Infection, held April 22-25, 1999, in Cannes, France, marked a shift in the direction of HIV nutritional investigation. [Ed. Note: All of the following reports were made at the conference by the presenters noted.]
WF10 is a novel treatment for HIV disease. An immune system modulator designed to enhance macrophage function, WF10 is intended for use as an adjunctive treatment, i.e., in addition to standard of care antiretroviral therapy in people with HIV. Studies already completed indicate that WF10 may be safely used by people with HIV and that the drug may be especially useful for people with moderate to advanced HIV disease.
Among anti-HIV drugs currently in the pipeline, BMS-232632, an HIV-1 protease inhibitor (PI) being developed by Bristol-Myers Squibb, displays significant promise. Based on early evidence showing it to be a powerful new agent against HIV replication, BMS-232632 has been slated for fast-track development. Preliminary studies indicate that it also could become the first PI ever to be approved for once-a-day dosing.
Inside the outpatient clinic building at the University of California, San Francisco (UCSF) Medical Center, on an overcast winter's day, seven women are seated around a table. Participants in a focus group, they are here to discuss their experiences and perspectives as older women living with HIV/AIDS.
My rational mind knows that I'm ten years older than when I was diagnosed. More often than not, however, I blame the ache or pain of unknown etiology on HIV, and rush to the doctor to see why I don't feel as well as my numbers look.
This issue's "Research Notes" features selected highlights from several recent conferences including the Second International Workshop on Salvage Therapy for HIV Infection (STHI) in Toronto, Canada, May 19-21, 1999, and the second annual Targeting HIV Reservoirs and Reconstituting the Immune System (THRRIS) meeting in Washington, DC, April 18-19, 1999.
At the STHI workshop, the topic of drug holidays was raised several times. A drug holiday refers to a temporary suspension of antiretroviral therapy. Very preliminary interim results from one study suggest a potential benefit from taking a drug holiday in persons who have experienced HIV viral load rebound ("drug failure") after significant prior anti-HIV drug exposure.
The U.S. Department of Health and Human Services has indicated its commitment to keeping the federal HIV treatment guidelines current as new clinical information is presented. (For previous changes to the guidelines.
E-biomed would be a new free electronic publishing Website for biomedical research results. The Website would allow for more rapid posting of new research results with instantaneous access from anywhere in the world. Traditional biomedical journal publishing could suffer due to competition.
HIV infection and changes in body metabolism have always gone hand in hand. The most evident sign of this relationship has been AIDS-related wasting syndrome, in which lean body tissues (muscle) are scavenged for energy resources.
Greg Szekeres, Claire Rappoport, and Donald Abrams, MD
Over the past two decades, the HIV epidemic in the United States has changed dramatically. Shifts in the demographics of those infected have been marked by steadily increasing rates among women, people of color heterosexuals, and youth.
The array of drugs now available to treat HIV infection and its associated conditions is the product of many hundreds of clinical trials involving tens of thousands of volunteers, if not more. As HIV/AIDS treatment has evolved, so has HIV-related research.
This issue of BETA features articles on metabolic side effects associated with anti-HIV therapy. This issue also presents two articles concerned with the current, somewhat tenuous state of HIV/AIDS clinical research today: "Volunteering for Clinical Trials," outlines issues particularly relevant to a person with HIV considering becoming involved with a clinical study, while "Current Challenges to HIV Research," delineates researchers' concerns. The issue also includes news summaries specific to women and HIV
In the past three years several new anti-HIV drugs have been approved by the Food and Drug Administration (FDA), including drugs belonging to two new classes, the non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the protease inhibitors.
Calanolide A is a new, experimental non-nucleoside reverse transcriptase inhibitor (NNRTI) and a synthetic version of a compound found in nature. The compound was discovered by researchers from the National Cancer Institute, who isolated it from extracts from the latex produced by a tree (Calophyllum lanigerum) native to the tropical rain forest of Sarawak, Malaysia.
Last November a critical study by researchers at the Johns Hopkins School of Public Health was published in the Lancet. Findings of the study, which was first presented at the 12th World AIDS Conference in Geneva in 1998, suggest that HIV viral load tests may be causing infection levels in women to be underrated.
Over 3,400 participants attended the 6th Conference on Retroviruses and Opportunistic Infections (CROI) held January 31-February 4, 1999 in Chicago. This conference is regarded as the most important annual research and clinical conference on HIV/AIDS in the United States.
One of the more interesting presentations at CROI was authored by researchers from the Fred Hutchinson Cancer Research Center at the University of Washington in Seattle. Research in the past several years has documented the existence of a small number of HIV negative persons who had a large number of high-risk, unprotected sexual exposures to HIV
As side effects associated with protease inhibitor therapy continue to increase, some people with undetectable HIV viral loads have expressed interest in switching to regimens based on NNRTIs. The major concerns associated with protease inhibitors center around abnormal increases in blood cholesterol and triglyceride levels and abnormal body fat redistribution, including lipodystrophy.
Promising New Double Protease Inhibitor Combinations Reported: Certain aspects of combination regimens with indinavir as the sole protease inhibitor present difficulties for some people with HIV.
Researchers from the Aaron Diamond AIDS Research Center in New York presented new information at CROI that may help to explain higher rates of HIV transmission among people of African descent. In the past two years, the discovery of a specific CCR5-D3 double gene mutation affecting immune cells helped to explain why certain high-risk gay men remained HIV negative.
The occurrence of several OIs is now better understood, according to research presented at CROI. These findings could eventually lead to specific tests that can help determine which people with HIV/AIDS need preventive therapy (prophylaxis) for selected OIs.
This information is designed to support, not replace, the relationship that exists between you and your doctor.