Good News and Bad News

From January 22 through the 26, 2,100 AIDS researchers and clinicians met in Washington, D.C. to discuss the latest findings in the clinical care of HIV-infected patients and recent findings in research on the pathogenesis of HIV. As with the International AIDS Conference in Vancouver, there was a great deal of exciting new information, particularly in the area of clinical care of HIV-infected patients. However, optimism was tempered by the fact that the HIV epidemic continues to escalate in many areas of the world, including the U.S., that new developments in treatment remain limited due to access issues, and HIV resistance continues to be problematic. Perhaps most disappointing was the lack of new advances in the field of HIV vaccine efficacy. Interestingly, the two keynote addresses at the opening session epitomized the conflict between optimism and pessimism. After Dr. David Ho of the Aaron Diamond AIDS Research Center speculated on the possibility of curing AIDS, Dr. Peter Piot of UNAIDS discussed the grim reality of the global AIDS epidemic, which continues to rage through many regions of the world.

First, the good news. Several presentations demonstrated that early and aggressive combination antiretroviral therapy begun shortly after infection can suppress viral replication in the peripheral blood and tissue reservoirs for up to 18 months. Mathematical models were presented which suggested that if viral load remains undetectable for a period of up to three years, then eradication and cure might be achievable. In addition, use of aggressive antiretroviral therapy in patients with CD4 cell counts between 200 and 500 appears to correlate with an improvement in immune responsiveness, providing additional hope for immune reconstitution in these intermediate-stage patients. However, several presentations suggested that treatment delayed until after the CD4 count has fallen below 100 cells/mm3 may not necessarily be associated with immune reconstitution. Despite increases in CD4 counts, opportunistic infection prophylaxis may need to be continued until we know more about the immunocompetence of treated individuals. It was also noted that antiretroviral drugs that reduce the amount of virus in the blood also markedly decrease the amount of HIV secreted in the semen and in the vagina, which may in turn reduce the risk of transmission. As stated by David Ho, "We obviously don't have a crystal ball, but the overall picture at the moment is that we can control the virus well, and we can have an impact on the disease for prolonged periods of time."

Several presentations emphasized the use of AZT during pregnancy to reduce the transmission of HIV from mother to infant. Since recommendations for the use of AZT in pregnancy were issued, the number of perinatally HIV-infected infants has declined by nearly two-thirds nationally. However, in some cities, particularly New York, the decline has been less (only 50%), reflecting problems with access to care and routine screening for HIV during pregnancy.

With the success of combination therapy in adults, pediatricians are also considering similarly aggressive therapy in perinatally-infected infants. In a study of twins, a triple-drug combination started at 10 weeks of age resulted in undetectable virus in one child for a period of 18 months. This infant has also lost all evidence of viral antibodies, suggesting possible viral eradication. While the child is still thought to carry HIV in her tissues, the investigators suggested that this may subside with continuing treatment. Her twin brother, who was also infected, started drug treatment at the same time and had an initial drop in viral load which was subsequently followed by the development of antiviral resistance. Thus, while combination therapy worked in one individual, it failed in a twin infected with the same virus and receiving the same drugs.

In the field of epidemiology perhaps the most exciting news presented at the conference was the marked decline in AIDS-related fatalities in New York City in 1996 compared to previous years. New York City, with 3% of the U.S. population, has 16% of all AIDS cases. More than 60,000 people have died from AIDS in New York City. Another 30,000 people are living with AIDS, and 100,000 are infected with HIV. As reported by Dr. Mary Ann Chiasson of the New York City Department of Health, mortality from AIDS increased steadily from 425 deaths in 1982 to 7,102 deaths in 1994. In 1995 New York's AIDS deaths fell slightly to 7,046, but in 1996, deaths fell substantially to 4,944, a 30% decrease (see figure). At the peak, there were about 20 AIDS related deaths per day, whereas in the spring of 1996 there were only 11.5 deaths per day. By November 1996 the rate declined further to 10.1 AIDS related deaths per day. It is not clear whether the decline in mortality is attributable to protease inhibitors, increased Ryan White funding for AIDS care, or both. For example, prior to the decline in mortality, New York City received $44 million in Ryan White funds for HIV care. Several months preceding the decline in mortality, New York City received an increase in Ryan White funds to an annual amount of $100 million. It was generally agreed that these Ryan White funds enabled new antiretroviral treatment to be provided to thousands of AIDS patients who otherwise could not afford it. In addition, the money provided expanded access to other therapies including treatment for pneumonia and drugs to prevent the development of opportunistic infections.

Consistent with this optimistic-pessimistic theme, however, it was also noted that while AIDS fatalities were decreasing due to improved treatment, the number of HIV-infected individuals developing AIDS continued to increase nationally and in New York City as well. The AIDS incidence among people between the ages of 13 and 25 rose by 17%, the largest increase of any age group. Nearly 35% of all new HIV infections in 1995 were among heterosexual women. Between 1990-1995, AIDS increased among heterosexuals by 131%, an increase of 73% among women and 56% among blacks. New cases of AIDS rose most dramatically (158%) among black heterosexual women, reflecting the shift in the epidemic to minority populations, to women, and to heterosexuals. Changes in mortality also varied by locality. In San Francisco, AIDS deaths continued to rise from 1,443 in 1995 to 1,517 in 1996. However, in Los Angeles, there was a 23% drop in AIDS deaths from 2,718 in 1995 to 2,084 in 1996.

An interesting presentation on the cost effectiveness of aggressive combination therapy demonstrated that while the cost of drug regimens has nearly tripled for people in advanced stages of disease, the total health care cost for these patients declined by 23% because of fewer hospitalizations and less need for home health care. For those patients with CD4 counts below 50 cells/mm3, traditionally the most expensive patients to care for, the total health care cost fell 31%. In one AIDS care center, combination therapy saved $250,000 per month. Three other centers estimated that AIDS-related expenses decreased by $100,000 per month due to the use of combination therapy. In several models there appeared to be a "threshold," a fraction of patients who had to be on drug combinations before the high cost was offset by savings gained in keeping patients healthier.

Despite a wide variety of advances in treatment, Dr. Peter Piot of UNAIDS reminded researchers, nearly 90% of HIV-infected people cannot access many of these new advances since they live in developing countries lacking the financial resources for treatment. He estimated that 8,500 people become infected with HIV each day. Of those, 1,000 are children under the age of 15, and nearly half of the remaining 7,500 are women, all of childbearing age and capable of passing the infection to their babies. Dr. Piot provided a glimmer of hope when he discussed successful prevention progress in countries such as Thailand, where a marked decline in unsafe sexual practices was associated with a decline in HIV incidence. Perhaps the most poignant comment of the meeting, though, was made by Dr. John Mellors, who stated, "We are winning a small battle in a war that is being lost." There is optimism for the individual in some places, but not a great deal of optimism for controlling HIV anywhere.