Cure Research for HIV/AIDS
Research discussion: NIAID-supported clinical trials have:
- demonstrated and defined the efficacy of zidovudine (AZT),
zalcitibine (ddC), didanosine (ddI) and stavudine (d4T) as
monotherapies and in combination regimens for a wide variety of
- demonstrated that combination regimens employing two or more
antiretroviral agents are more effective than AZT monotherapy,
particularly early in disease.
- defined the standard of care for acute treatment and
prophylaxis of Pneumocystis carinii pneumonia, treatment
and maintenance for cryptococcal meningitis (fluconazole),
treatment and maintenance therapy for disseminated histoplasmosis
(itraconazole), treatment of disseminated Mycobacterium
avium complex (clarithromycin), management of cytomegalovirus
retinitis and acyclovir-resistant herpes simplex (foscarnet).
- assessed and validated assays for use as surrogate markers of
drug effectiveness including p24 antigen, quantitative peripheral
blood mononuclear cells (PBMC), microculture and DNA/RNA (PCR).
- developed state-of-the-art study design methodology for HIV disease (e.g., endpoints) to permit rapid clinical and laboratory evaluation of antiretroviral compounds.
NIAID's pediatric clinical research effort has significantly advanced the treatment and prevention of HIV infection in infants and children. Through clinical trials, NIAID has:
- demonstrated that AZT therapy reduced dramatically the likelihood of childhood HIV infection resulting from transmission from infected mothers during pregnancy or delivery.
- demonstrated that ddI or ddI plus AZT are superior to AZT monotherapy for children with symptomatic HIV infection or AIDS.
- demonstrated the effectiveness of IVIG for preventing serious bacterial infections in children with HIV.
- developed guidelines for the prevention of PCP in HIV-infected children.
Over the next several years, NIAID research will continue to define the standard of care for HIV-infected people of all ages. Particular emphasis will be placed on the use of combination regimens with protease inhibitors.1
NIAID-supported investigators are
conducting an abundance of research on HIV infection, including
developing and testing HIV vaccines and new therapies for the
disease and some of its associated conditions. Investigators are
testing 29 HIV vaccines in people, and are developing or testing
many drugs for HIV infection or AIDS-associated opportunistic
infections. Researchers also are investigating exactly how HIV
damages the immune system. This research is suggesting new and more
effective targets for drugs and vaccines. NIAID-supported
investigators also continue to trace how the disease progresses in
Scientists are investigating and testing chemical barriers, such as topical microbicides, that people can use in the vagina or in the rectum during sex to prevent HIV transmission. They also are looking at other ways to prevent transmission, such as controlling sexually transmitted diseases and modifying people's behavior, as well as ways to prevent transmission from mother to child. 2
Because HIV is spread
predominantly through sexual transmission, the development of
chemical and physical barriers that can be used intravaginally or
intrarectally to inactivate HIV and other sexually transmitted
disease (STDs) pathogens is critically important for controlling HIV
Scientists are developing and testing new chemical compounds that women could apply before intercourse to protect themselves against HIV and other sexually transmitted organisms. These include creams or gels, known as topical microbicides, which ideally would be non-irritating and inexpensive. In addition, microbicides should be available in both spermicidal and non-spermicidal formulations so that women do not have to put themselves at risk for acquiring HIV and other STDs in order to conceive a child. The research effort for developing topical microbicides includes basic research, preclinical product development, and clinical evaluation.
A small study of low-risk women in the United States recently tested the safety of BufferGel, a microbicide that helps maintain the healthy acidic environment of the vagina in the presence of semen. This in turn helps protect women against HIV and other sexually transmitted pathogens. This U.S.-based study found BufferGel to be safe and generally accepted. A subsequent study was then conducted in India, Thailand, Malawi, and Zimbabwe and found that compliance and use of the BufferGel was high. Because there were no major safety concerns reported in either the domestic or international studies, research is underway to evaluate the effectiveness of BufferGel in preventing HIV infection.
Transmission of HIV from Mother to Infant
In the United States, approximately 25 percent of pregnant HIV-infected women who do not receive AZT or a combination of antiretroviral therapies pass on the virus to their babies. If women do receive a combination of antiretroviral therapies during pregnancy, however, the risk of HIV transmission to the newborn is below 5 percent.
The risk of mother-to-infant transmission is significantly increased if the mother has advanced HIV disease, large amounts of HIV in her bloodstream, or fewer-than-normal amounts of the immune system cells (CD4+ T cells) that are the main targets of HIV.
Other factors that may increase the risk include
- Drug use, such as heroin or crack/cocaine
- Severe inflammation of fetal membranes
- A prolonged period between membrane rupture and delivery
Most mother-to-infant transmission, an estimated 50 to 70 percent, probably occurs late in pregnancy or during birth. Although the exact ways the virus is transmitted are unknown, scientists think it may happen when the mother's blood enters the fetal circulation, or by mucosal exposure to virus during labor and delivery. Research is underway to identify the mechanisms of mother-to-child transmission of HIV and to develop interventions to reduce it. Notably, NIAID-funded investigators have identified two regimens that reduce mother-to-infant transmission of HIV. The first regimen to prevent mother-to-infant transmission of HIV was identified in a landmark study conducted in 1994 by the Pediatric AIDS Clinical Trials Group. It involved a specific regimen of AZT given to an HIV-infected woman during pregnancy and to her baby after birth and was shown to reduce mother-to-infant HIV transmission by two-thirds.
In another NIAID-sponsored study in Uganda, researchers identified a highly effective and safe drug regimen for preventing transmission of HIV from an infected mother to her newborn that is also more affordable and practical than any other examined to date. The study demonstrated that a single oral dose of the antiretroviral drug nevirapine given to an HIV-infected woman in labor and another dose given to her baby within three days of birth reduces the transmission rate by about half compared with a course of AZT given only during labor and delivery. This study suggests that women in the United States who are identified very late in pregnancy or at the time of labor and delivery could also have lower rates of transmission of HIV to their infants by following a nevirapine-containing regimen.
HIV also may be transmitted from a nursing mother to her infant. A series of studies have determined that breastfeeding increases the risk of HIV transmission by about 14 percent. Currently, the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommends that HIV positive women be educated and counseled so they can make an informed decision about how to best feed their infant. Research is underway in areas of the world where the benefits of breastfeeding outweigh the risks to identify effective strategies for reducing the risk of transmission through breastfeeding. This includes early weaning strategies, as well as the evaluation of drugs or vaccines to reduce the risk of transmission from breastfeeding.
Transmission of HIV to Women Worldwide, WHO estimates that more than 80 percent of adult HIV infections are due to heterosexual transmission of the virus through sexual intercourse. In the United States, the majority of women are infected with HIV during sex with an HIV-infected man or while using HIV-contaminated syringes for the injection of drugs such as heroin, cocaine, and amphetamines. Of the new AIDS cases reported among women in the United States in December 1999, 40 percent were attributed to heterosexual contact and 27 percent to injection drug use. The majority of the remaining cases had no identifiable risk.
In the United States, studies have shown that during unprotected heterosexual intercourse with an HIV-infected partner, women have a greater risk of becoming infected than do uninfected men who have heterosexual intercourse with an HIV-infected woman. In other parts of the world, however, this is not necessarily true. In Uganda, for example, one study demonstrated that the risk of HIV transmission from a woman to man was the same as from a man to woman. This difference may be due to the lack of circumcision in Ugandan men.
Studies in both the United States and abroad have demonstrated that STDs, particularly infections that cause ulcerations of the vagina (e.g., genital herpes, syphilis, and chancroid), greatly increase a woman's risk of becoming infected with HIV. NIAID-sponsored cohort studies in the United States have also found a number of other factors to be associated with an increased risk of heterosexual HIV transmission, including alcohol use, history of childhood sexual abuse, current domestic abuse, and use of crack/cocaine.
The consistent and correct use of male latex condoms greatly reduces the risk of becoming infected with HIV. In studies of heterosexual couples, in which one individual was HIV-positive and the other uninfected and regular condom use was reported, the rate of HIV transmission has been extremely low.3
The Pharmaceutical Research and Manufacturers Association lists nearly two dozen new anti-HIV drugs now in development. They include new protease inhibitors and more potent, less toxic RT inhibitors, as well as drugs that interfere with entirely different steps in the virus' lifecycle. These new categories of drugs include
- Fusion inhibitors -- drugs that interfere with HIV's ability to enter a cell
- Integrase inhibitors -- drugs that interfere with HIV's ability to insert its genes into a cell's normal DNA.
In addition, scientists are learning how immune modulators help boost the immune system's response to the virus and may make the existing anti-HIV drugs more effective. Therapeutic vaccines are also being evaluated for this purpose and could help reduce the number of anti-HIV drugs needed or the duration of treatment.4
Medical research for HIV/AIDS: medical news summaries: The following medical news items are relevant to medical research for HIV/AIDS:
- AIDS cure progressing
- Anti-retroviral drug trial may have led to pregnant woman’s death
- HIV patients face increased risk of diabetes and dementia
- Long-term effects anti-retroviral treatment for AIDS being studied
- NIAID talks down concerns over HIV/AIDS drug
- Researchers examine how to reduce toxoplasmosis encephalitis in HIV patients
- Tuberculosis in children may be diagnosed using simpler test
- Women too are at risk of lung cancer
1. excerpt from Clinical Trials for AIDS Therapies, NIAID Fact Sheet: NIAID
2. excerpt from HIV Infection and AIDS, An Overview, NIAID Fact Sheet: NIAID
3. excerpt from HIV Infection in Women, NIAID Fact Sheet: NIAID
4. excerpt from Treatment of HIV Infection: NIAID
Last revision: April 2, 2003
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