HIV, or human immunodeficiency virus, is the virus that causes AIDS (Acquired Immune Deficiency Syndrome). HIV kills or damages cells of the body's immune system (particularly cells called CD4-positive [CD4+] T cells, or T helper cells, which is a type of white cell vital to fighting infection). This destroys the body's ability to fight infections and certain cancers.
The most advanced stages of HIV infection are known as AIDS. HIV can be transmitted through sexual contact, contaminated needles or syringes, contaminated blood products, and transmission from mother to child during pregnancy, the birth process, or breast milk.
The NICHD is one of many federal agencies and NIH Institutes working to understand HIV/AIDS. Unlike other Institutes and agencies, the NICHD's research focuses on the biology, prevention, and treatment of HIV/AIDS in women (including pregnant women), infants, children, and adolescents.
Another Institute—the National Institute of Allergy and Infectious Diseases (NIAID)—leads HIV/AIDS research at the NIH and conducts and supports research on more general aspects of the disease. Information provided in the Condition Information section of this website is specific to the populations that the NICHD studies; links to more general HIV/AIDS information from the NIAID are also provided.
- SIDA in Spanish
Medical or Scientific Name
- Human Immunodeficiency Virus
- Acquired Immune Deficiency Syndrome
HIV/AIDS: Condition Information
What is HIV/AIDS?
HIV kills or damages cells of the body's immune system. This damage progressively destroys the body's ability to fight infections and certain cancers.
The most advanced stages of HIV infection are known as AIDS. People with AIDS are at great risk of getting very sick from diseases that don't normally affect healthy people. These include viral infections that cause skin tumors and pneumonia, fungal infections of the mouth, lungs, and genitals, and certain cancers. AIDS was first reported in the United States in 1981; it is now recognized that HIV is a major worldwide epidemic.
The National Institute of Allergy and Infectious Diseases (NIAID) has a more comprehensive description of HIV/AIDS.
For information about how many people have HIV/AIDS, visit https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics.
How does HIV cause AIDS?
HIV destroys vital cells of the immune system, called CD4+ T cells. Once enough of these cells are destroyed, the person is considered to have AIDS. This means that the person's immune system has weakened considerably.
A healthy person has between 800 and 1200 CD4+ T cells in one cubic millimeter (about 1/50,000 of a teaspoon) of blood. AIDS occurs when there are fewer than 200 CD4+ T cells per cubic millimeter.
NIAID provides more information about how HIV leads to AIDS.
Is there a cure for HIV and AIDS?
There is currently no cure for HIV/AIDS, but there are effective treatment options that can keep the HIV infection under control and prevent AIDS. Read more about HIV treatments. https://www.nichd.nih.gov/health/topics/hiv/conditioninfo/treatments
The best option is always prevention. Read more about preventing HIV infection. https://www.nichd.nih.gov/health/topics/hiv/conditioninfo/prevent
What are the symptoms of HIV/AIDS?
People with an HIV infection experience different symptoms in the early and late stages of infection. Mostly, these symptoms are the same in women and men, but some symptoms are unique to women.
At first, a person with HIV will not have any visible symptoms.
|HIV symptoms can also be similar to those caused by other illnesses.
An HIV test is the only way to tell for sure whether you have HIV.
A few weeks after infection, many people have flu-like symptoms, which then disappear after a while. These symptoms can include fever, headache, tiredness, and enlarged lymph glands in the neck and groin area. Other people infected with HIV may have no symptoms.
However, even if people with HIV feel healthy, HIV is still affecting their bodies. Once HIV enters the body, it infects large numbers of CD4+ cells and rapidly spreads throughout the body and into many organ systems. During this early period, people with HIV are more likely to spread the infection during unprotected sex or other risky situations because HIV is present in large amounts in genital fluids and in blood.
HIV infection is associated with many medical conditions, including frequent or unusual infections, heart disease, kidney disease, liver disease, and cancer. If not treated, some people with HIV have severe symptoms at first, but others have no symptoms for 10 years or more.
AIDS is the late stage of HIV infection, when a person's immune system is severely weakened and has difficulty fighting infections and certain cancers. At this stage, serious symptoms occur that can include rapid weight loss; serious infections; pneumonia; recurrent fevers; prolonged swelling of the lymph glands; blotches on the skin; prolonged diarrhea; sores of the mouth, anus, or genitals; and memory loss, depression, and other neurologic disorders.
The National Institute of Allergy and Infectious Diseases has more comprehensive information about the symptoms of HIV/AIDS.
Signs and Symptoms of HIV/AIDS in Infants and Children
HIV infection is often difficult to diagnose in very young children. One the one hand, infants with HIV often appear normal and may show no signs allowing for a clear diagnosis of HIV infection. On the other hand, many infants develop multiple and serious illnesses related to their HIV infection.
Many children with HIV infection do not gain weight or grow normally. If left untreated, HIV-infected children are frequently slow to reach important milestones in motor skills and mental development, such as crawling, walking, and talking. As the disease progresses, many children with untreated HIV develop problems with walking, poor school performance, seizures, and other symptoms of HIV brain encephalopathy (a brain infection).1
Children with untreated HIV suffer the usual childhood infections more frequently and more severely than HIV-uninfected children. These infections can cause seizures, fever, pneumonia, recurrent colds, diarrhea, dehydration, and other problems that often result in extended hospital stays and nutritional problems. Like adults with HIV infection, children with HIV are at risk of developing life-threatening opportunistic infections. Pneumocystis pneumonia (PCP), a severe form of pneumonia that strikes people with weakened immune systems, is common and sometimes deadly in infants who do not receive treatment for their HIV infection.1
How does HIV/AIDS affect women?
Throughout the world, HIV is most often spread through sex.1 Women may be at greater risk of being infected with HIV during sexual contact than men are. This is because the fragile tissues of the vagina can tear slightly during sex and let the virus enter the body. (This is especially likely among girls under age 18.) The vagina also has a large surface area that can be exposed to the virus, thus increasing risk of infection. Similarly, anal tissues are also fragile and prone to tearing slightly during sex. Women are at higher risk of infection via anal sex than by vaginal sex with an infected man. Most women around the world and in the United States who have HIV were infected through sex with a man.
Forced sex, transactional sex, and marriage to much older men increase women's risk of infection in many places around the world. The World Health Organization has more information on gender inequality and HIV .
Having multiple sex partners can also increase the risk of exposure to the virus that causes the disease. Injection drug use is another way HIV can be acquired by women.
Signs and Symptoms
Most signs and symptoms of HIV/AIDS are the same in men and women. However, there are some that are specific to women. For example:
- Vaginal yeast infections. These infections can be more severe and difficult to treat in women with HIV infection than in other women. Yeast infections can also be chronic in women with HIV, which means that the infection is long-lasting or keeps coming back.
- Pelvic inflammatory disease. This infection of the female reproductive organs may be more frequent and severe in women with HIV infection. Additional information on pelvic inflammatory disease is available from the National Institute of Allergy and Infectious Diseases.
- Human papillomavirus (HPV) infections. HPV causes genital warts and can lead to some cancers, especially cancer of the cervix. HPV infections may be more likely to cause warts or pre-cancerous changes in the cervix in HIV-infected women than in HIV-uninfected women.
The NICHD, along with other Institutes, supports studies to determine what aspects of HIV are specific to women and the best treatments for these symptoms.
The Centers for Disease Control and Prevention collects detailed statistics on HIV in the United States. It has more information about HIV and women in the United States.
Women who have HIV can pass the infection to their children during pregnancy, birth, and breastfeeding. For this reason, pregnant women who are HIV-infected need to take extra steps to protect their children from infection. These steps include taking anti-HIV drugs and formula-feeding their children. Using contraception to prevent unintended pregnancy is another method to prevent transmission of the virus, and it's very effective and inexpensive . Read more about preventing mother-to-child transmission of HIV.
How is HIV spread?
HIV lives in an infected person's blood , tissues, organs, and certain body fluids (semen or vaginal fluid and anal mucus).1,2 Nursing mothers who are infected also have HIV in their breast milk. HIV spreads between people through blood and body fluids.
There are several common ways that HIV can be passed from person to person, including:
- Having unprotected sex with someone who is infected. Worldwide, most new HIV infections occur through sex.3 Women are particularly at risk of infection through sex. It's much easier to get HIV (or to give it to someone else) if a person has a sexually transmitted disease (STD). For more information, see the Centers for Disease Control and Prevention's The Role of STD Detection and Treatment in HIV Prevention.
- Transmission from mother to child. Without anti-HIV treatment, an infected mother may pass the virus to her child during pregnancy, birth, or breastfeeding. Although mother-to-child transmission is preventable, and transmission is rare in the United States, more than 300,000 infants are infected each year through their mothers globally; most of these infections occur in sub-Saharan Africa.
- Using needles or syringes that have been used by people who are infected.
- Pre-chewing food for infants. In a few cases, HIV has been spread when HIV-infected caregivers chewed food (or warmed it in their mouths) and then fed the food to an infant. This practice can expose the child to HIV if the caregiver has a sore or cut in the mouth. The CDC recommends that HIV-infected caregivers do not pre-chew food for infants.4
- Receiving infected blood products or transplanted organs. Since 1985, the United States tests all donated blood and organs for HIV; therefore, the risk of getting HIV in this way in the United States is now extremely low, and the risk is also decreasing in other countries as they improve their testing methods. For more information, see the CDC's How safe is the blood supply in the United States?
How does HIV affect children & adolescents?
Children of women with HIV are at risk of infection when they are still in the womb, during birth, and while breastfeeding. Many children and youths now living with HIV were infected at birth. Effective drugs against HIV now allow these children to survive and grow into adulthood.
In the United States, new infections at birth are now very rare because of drugs that pregnant women can take that can block HIV transmission to the child. It is important to start these drugs early in pregnancy. In parts of the world where pregnant women do not have access to these drugs, the rate of infection among infants is much higher. Before such drugs were available, about 25% of infants of HIV-infected women in the United States would become HIV-infected; now, less than 2% of HIV-infected women in the United States will pass infection to their infants.1 Read more about mother-to-child transmission of HIV.
Unprotected sexual activity can lead to new infections. The Centers for Disease Control and Prevention's (CDC) national Youth Risk Behavior Survey and other CDC data have identified risk factors that can increase adolescents' and young adults' risk of HIV infection. These include:2
- Male–male sex. Young men who have sex with men, especially African Americans and Latinos, have high rates of new HIV infections. This may be because this group is less likely to be aware of their infections than other young people who are HIV positive. Another reason may be that these young people have been less likely to receive relevant, effective prevention education and interventions.
- Early sex. By age 16, about one-third of boys and girls have had sex.3,4
- Sex with older partners or with a number of partners. This may increase teens' infection risk.
- Use of alcohol or drugs before sex. This can affect decision making about whether to engage in sex or to use protection during sex.
- Not knowing HIV status. Most of the undiagnosed HIV infections in the United States are among young people aged 13–24.5 Youths who are at the highest risk of infection (males who have sex with males and minority youth) are not only more likely to be infected, but also they are the most likely to not get tested for HIV. This risks their own health and the health of people with whom they have sex.
A study co-funded by the NICHD and the National Institute of Allergy and Infectious Diseases found that American children with HIV are surviving in greater numbers than ever before. Due to anti-HIV drugs, the number of deaths among children with HIV has dropped to one-ninth of its former level. However, children with HIV are still 30 times more likely to die than other children. Organ failure and kidney disease are often responsible. Read more about this study.
The CDC collects detailed data on HIV in the United States. It has more information on HIV and youth in the United States.
How is HIV not spread?
There is no evidence that HIV is spread by:
- Contact with saliva, tears, or sweat
- Shaking hands
- Sharing food utensils
- Sharing linens, like towels and bedding
- Swimming in the same pool
- Normal contact children experience in schools and homes
- Using the same telephone
- Using the same toilet seats
- Bites from insects or other animals
Who is at risk of HIV/AIDS?
HIV can infect anyone whose blood comes into contact with an infected person's blood, breast milk, or sexual fluids. Some people engage in behaviors which place them at greater than normal risk. For example:
- Risky, unprotected sexual behaviors, like having sex without a condom and having multiple sex partners, can increase someone's chance of getting infected. These sexual risk behaviors are common among teens and young adults, who have very high rates of HIV infection compared to other Americans. Read more about young people and HIV. Additionally, men who have sex with men and individuals who have anal sex are at high risk of infection.
- Exposure to the virus as a fetus or infant before or during birth or through breastfeeding from a mother who is HIV positive.
- People with other sexually transmitted infections, such as chlamydia, gonorrhea, syphilis, bacterial vaginosis, and herpes, increase their risk of getting infected if they are exposed to the virus through sex or blood exposure.
- Using drugs can increase risk. Sharing needles or syringes to inject drugs or steroids can pass the virus. Drug use can also make people take risks they would not ordinarily take, like having risky, unprotected sex.
- People who received blood products in the United States between 1978 and 1985 before all blood was tested may have been exposed to the virus.
- Infants who are fed food that has been pre-chewed by an HIV-infected person may be at higher risk. HIV in blood in the caregiver's mouth can mix with the food while chewing; this is a rare occurrence and has been reported only in infants.
The Centers for Disease Control and Prevention has more information about HIV transmission.
How do health care providers diagnose HIV/AIDS?
|More than 1 out of every 5 Americans with HIV may not know they're infected. Do you know your status? Find an HIV testing site near you at https://www.cdc.gov/hiv/testing/index.html.|
The most common tests examine a blood sample for evidence that a person's body is fighting an HIV infection. These tests detect HIV antibodies, which are substances the body creates in response to being infected with HIV.
However, during the first several weeks of infection, these tests may not reveal the infection. This is because it takes some time for the immune system to produce enough antibodies for the antibody test to detect. This is a time when it is very easy for a person with the virus to pass it on to someone else. Ninety-seven percent of people will develop detectable antibodies in the first 3 months after infection, but for a small percentage of people it can take longer). In these cases, different tests can directly look for pieces of the virus's genetic material in the blood.
Diagnosis in Children and Youth
There are special challenges in diagnosing HIV in infants and youth.
Because the HIV antibody from HIV-infected mothers passes to their infants, finding the HIV antibody in an infant does not indicate that the infant has become HIV-infected. Maternal HIV antibody in an uninfected infant can persist as long as 12 to 18 months before it disappears. Therefore, an HIV antibody test cannot be used to diagnose HIV infection in infants younger than age 18 months.
Scientists have developed highly accurate blood tests for diagnosing HIV infection in infants. One laboratory test, called polymerase chain reaction, can detect extremely small quantities of HIV's genetic material in an infant's blood and allow a diagnosis to be made in the first few months of life.1
The challenge in youth is different: Many young people think they're not at risk for HIV. This makes them less likely to seek testing. As a result, the Centers for Disease Control and Prevention recommends routine HIV screening in health care settings starting at age 13. The U.S. Preventive Services Task Force recommends routine screening for HIV infection beginning at age 15 years or earlier for adolescents at increased risk.
What are the treatments for HIV?
There are many drugs approved to fight HIV. However, these drugs:
- Do not cure HIV or AIDS
- Do not stop the virus from spreading from person to person, although they do make transmission less likely
HIV drugs keep the virus from multiplying in the body. This helps to keep people with an HIV infection from developing AIDS and helps them live longer, healthier lives. However, it is still possible to transmit the virus to others, and people must continuously take the antiretroviral drugs to stay healthy.
People with AIDS or advanced HIV often get other illnesses due to their weakened immune systems. There are treatments available for many of these other illnesses.
The National Institute of Allergy and Infectious Diseases has more information about HIV treatments.
Treatment Concerns for Women
For the most part, HIV/AIDS treatments for women are the same as for men.
However, there are some special concerns related to treatment of HIV in women and pregnancy and pregnancy prevention:
- Birth control. Some anti-HIV drugs interact with birth control pills. This may mean that a woman on HIV medication is more likely to become pregnant even if she's using contraception. HIV-infected women who want to avoid pregnancy should talk to their health care providers about the safest and most effective birth control method for them. Pregnant women are more likely to get infected if exposed to the virus, so use of condoms is important during pregnancy.
- Birth abnormalities. One anti-HIV drug, called efavirenz or Sustiva, may rarely be associated with abnormalities of birth if a woman takes it during the first trimester of pregnancy.
- Mother-to-child transmission. During pregnancy, birth, and nursing, HIV can pass from a mother to her child. Women can avoid this if they and their infants take anti-HIV drugs and avoid breastfeeding. Read more about preventing mother-to-child transmission of HIV.
The Department of Health and Human Services Office on Women's Health has more comprehensive information for women on HIV treatment.
How can I prevent myself or my child from getting HIV?
HIV is spread only in certain ways and you cannot get it through everyday contact. You can reduce your risk if you:
- Have sex only with your spouse or partner, and be sure that he or she only has sex with you.
- Consistently use male latex or female polyurethane condoms if you have sex.
- Do not share needles.
Unlike many other infections, like measles and polio, there is not yet a vaccine for HIV.
The National Institute of Allergy and Infectious Diseases has more general information about how to prevent the spread of HIV.
Without any interventions, a newborn is at higher risk of getting HIV from its infected mother. Without breastfeeding and with no other interventions, about one-quarter of infants will get HIV. With breastfeeding and with no other interventions, about one-half of infants will get HIV. Prevention strategies and interventions can reduce this risk to less than 2%.1
Prevention strategies can reduce this risk to less than 2%.1 If you are a pregnant woman concerned about HIV, experts recommend that you:
- Get an HIV test. If you know you have HIV, you can take steps to lower your baby's risk for infection.
- If you have HIV, take anti-HIV drugs for yourself and your child. You should take anti-HIV drugs during pregnancy, labor, and birth, and your child should take them for the first weeks of life.
- If you have HIV, avoid breastfeeding. HIV can pass from you to your child through your breast milk. If you live in the United States or another country with safe water, formula feeding is best for prevention of HIV.
The NICHD is heavily involved in finding ways to prevent mother-to-child transmission of HIV. Read about the research advances in this area through the links on the Publications and Resources page.
Treatment Considerations for Children and Teens
Because of their developing bodies, children and teens have to take different amounts, formulations, and combinations of anti-HIV drugs than adults.
Children and youth might also require special treatments for side effects of HIV or anti-HIV drugs. For example, the widely used anti-HIV drug tenofovir can make youths' bones weaker and could endanger their long-term bone health. NICHD-sponsored research found that vitamin D pills may prevent this problem.
The best treatment strategy may be different for each child or teen. These are some factors that affect treatment:
- Time of infection. HIV infections are different in young people who were infected at birth or in infancy versus those who were recently infected. HIV infection may progress rapidly to death in infants who are infected at birth. Because of this, it is recommended that all HIV-infected infants under age 12 months be started on anti-HIV drugs as soon as possible, even if they don't have symptoms. In older children, evaluation of their immune cells (CD4+ cells) and symptoms are used to help determine when they should start anti-HIV therapy.
- Availability of pediatric anti-HIV drug formulations. Young infants cannot swallow pills or capsules and therefore require special drug formulations, such as liquids. Not all anti-HIV drugs available for adults have formulations that infants and young children can take.
- Availability of pediatric dosing information. The doses of anti-HIV drugs that need to be given are different in children than adults, and also vary in children of different ages. Not all anti-HIV drugs approved for adults have been studied in children to know the right dose for children. Additionally, dosing information for some anti-HIV drugs may be available for older but not younger children.
- Prior anti-HIV treatment. Some anti-HIV treatments stop working after a period of time because the HIV virus may become resistant to those drugs. For example, teens who were infected at birth might harbor HIV that has become resistant to some drugs during periods when they have trouble taking anti-HIV drugs that kept their HIV blood levels (viral load) controlled. See "treatment adherence" below.
- Treatment adherence. Many children and teens are concerned about fitting in with their friends and may not think about future consequences as much as adults do. For these and other reasons, some have trouble taking their medication as directed. If medication is not taken correctly or as directed (called poor drug adherence), the virus may become resistant to the drugs. Many strategies can help improve treatment adherence among youth, including simpler treatment plans, text message reminders for taking pills, and support from HIV-infected peers.
The NICHD-supported Adolescent Trials Network (ATN) is focused on finding the best treatments for youths who are HIV-infected or at risk of infection. The ATN has more information about what it does and how to participate.
HIV/AIDS: NICHD Research Goals
The NICHD supports and conducts research on a wide range of topics within HIV/AIDS, including the pathogenesis, epidemiology and demographics, prevention, and treatment of HIV and co-occurring infections. These topics include:
- Understanding the contexts (including social, institutional, economic, cultural, and geographic), patterns, and impact of sexual behavior and HIV transmission, testing, and treatment in populations.
- Uncovering factors that influence decisions and behaviors that affect HIV risk. Information about the sources of vulnerability to infection is important to inform interventions in diverse populations.
- Conducting basic research to elucidate the biological and molecular mechanisms of HIV transmission, replication, and reservoirs, particularly those unique to pregnant women, fetuses, infants, children, and adolescents. Knowledge of cell- and molecule-level pathways that are involved in HIV disease may lead to new preventative or therapeutic interventions for the infection.
- Developing and evaluating prevention and therapeutic strategies specifically for pregnant women, infants, children, and adolescents, including a special focus on prevention of mother-to-child transmission. These strategies may be nutritional, social, behavioral, pharmacological, immunological, or others. Interventions for HIV infection, adherence to anti-HIV medications, co-infections, side effects of treatment, or other complications or consequences of HIV infection (such as social consequences) are all needed.
- Evaluating diagnosis, prevention, and therapeutic strategies for co-infections, including tuberculosis, hepatitis, and malaria, that are common in HIV-infected women, infants, children, and adolescents, particularly in resource-limited countries.
- Understanding the impact of HIV infection and its treatment on women and children globally. These include the effects on pregnancy, fetal development, child development (including growth, sexual maturation, metabolism, socialization, and neurology), and gender-specific aspects of HIV (such as interaction between HIV and female hormones through the life span, effects on bone, and cervical or breast disease or cancer).
- Characterizing the impacts of pregnancy and childhood development on HIV therapies, including determination of appropriate drug formulations and dosing regimens for these populations.
- Understanding anti-HIV drug toxicity in pregnancy, in utero, and in infancy and the long-term effects of early antiretroviral exposure on all aspects of child development, including effects of in utero anti-HIV drug exposure on HIV-exposed but uninfected children.
- Determining the safety and efficacy of contraceptives and infertility treatments in HIV-positive women.
- Developing and improving methods for studying sexual behavior, including reliable and unbiased measures, data collection methods that improve validity of self-reports, and methods for validation of self-report data.
- Developing capacity for HIV/AIDS research in resource-limited nations through training and improved infrastructure.
- Improving diagnosis and monitoring of perinatal and pediatric HIV infection and co-infections, especially through assays and strategies that are appropriate for use in developing nations.
HIV/AIDS: Research Activities and Scientific Advances
NICHD components support and/or conduct research on the following aspects of HIV/AIDS.
Basic Research on HIV/AIDS
Behavioral Health Aspects of HIV/AIDS
Demographics of HIV/AIDS & Sexually Transmitted Infections (STIs)
Preventing Mother-to-Child Transmission of HIV/AIDS
Effects of HIV/AIDS Drugs on Pregnancy & Development
HIV/AIDS in Women
HIV/AIDS in Adolescents
HIV/AIDS in Children
HIV/AIDS Therapeutics & Vaccine Development
Nutrition & HIV/AIDS
Building Capacity for HIV/AIDS Research
Both extramural and intramural entities within NICHD are involved in basic research related to HIV/AIDS.
Hormones & HIV
The effect of endogenous and exogenous steroid hormones on risk of HIV acquisition, transmission, and disease progression is unknown. The Contraceptive Discovery and Development Branch (CDDB) and the Maternal and Pediatric Infectious Disease Branch (MPIDB) both fund extramural research on this topic.
The HIV Genome
In NICHD's intramural program, three sections investigate some aspect of HIV genome replication:
- Reverse transcription. The goal of the Section on Viral Gene Regulation, part of the Program on Genomics of Differentiation within the NICHD Division of Intramural Research (DIR), is to define the molecular mechanisms responsible for the replication of HIV and related mammalian retroviruses and to investigate the role of host proteins that block virus infection. These studies help to identify new targets for anti-HIV therapy and are critical for developing novel strategies to combat the AIDS epidemic. Research is currently focused on several broad areas of interest: (i) reverse transcription and the critical role of the HIV-1 nucleocapsid protein in this process; (ii) molecular characterization, biological activity, and structure of human defense proteins APOBEC3G and APOBEC3A, which are cytidine deaminases that inhibit HIV-1 replication; and (iii) structure-function analysis of the HIV-1 capsid protein and its essential role in proper assembly of HIV-1 particles and the ability of virions to undergo reverse transcription.
- RNA/DNA hybrids. The research of the Section on Formation of RNA in the DIR Program on Genomics of Differentiation investigates the formation and resolution of RNA/DNA hybrids, which are essential intermediates in the replication of HIV's genome. In addition to their presence in HIV replication, RNA/DNA hybrids are omnipresent intermediates in normal DNA replication and RNA synthesis but when mishandled can cause human diseases and disorders.
- Genomic integration. The Section on Eukaryotic Transposable Elements, of the Program in Cellular Regulation and Metabolism, uses a retrotransposon in the fission yeast genome as a model for understanding how retroviruses like HIV insert their genetic material into the host cell genome. In particular, the Section's research aims to determine the viral genome's mechanisms of selecting its target integration sites.
Other HIV Basic Biology
Three other intramural entities study some aspect of HIV basic biology:
- Copathogens. The Section on Intercellular Interactions, in the DIR Program in Physical Biology, focuses on understanding the pathogenesis of HIV in human tissues, particularly the virus' interactions with copathogens and these interactions' effects on determining the mechanisms of HIV-1 transmission and the course of HIV infection. In 2011, research conducted by this section and non-NIH collaborators discovered the mechanism behind the anti-HIV drug tenofovir's activity against genital herpes in vaginal gel formulation. The research found that this surprise effect, uncovered in a clinical trial earlier that year, is due to the drug's inhibition of a viral DNA synthesis. This basic research finding may illuminate new avenues of research on drugs with dual activity against both genital herpes and HIV.
- Immune system proteins. Another recent discovery by the Section on Intercellular Interactions involves immune system protein normally found in semen that occurs in high levels in the semen of men with HIV. Researchers observed that HIV-infected T cells targeted by the protein lived longer and continued to make more of the virus.
- CD4 downregulation. The Juan Bonifacino Lab in the DIR Cell Biology and Metabolism Program investigates the molecular mechanisms by which transmembrane proteins are sorted to intracellular compartments. One current project studies the downregulation of the CD4 protein in viral host cells, T-lymphocytes, and macrophages by two HIV-1 proteins, Nef and Vpu. Knowledge of these pathways could provide new avenues for therapeutic intervention.
Behavioral Health Aspects of HIV/AIDS
The Population Dynamics Branch (PDB) is the principal NICHD entity supporting research on behavioral and other aspects of HIV/AIDS. It also sponsors the development and improvement of methods for studying sexual behavior. The Branch funds extramural research investigating the interrelationships among social, institutional, economic, and cultural contexts and sexual behavior. It also supports efforts to develop and evaluate behavioral interventions that are relevant within these contexts.
Branch-supported research in this area includes studies of the onset and trajectories of sexual activity, contraceptive use, and sexual partnerships and research on partnership dynamics and characteristics. The Branch also is interested in studies of the consequences of sexual behaviors and related aspects of reproductive health for individual well-being, interpersonal relationships, reproductive outcomes, and the well-being of families, communities, and society.
For example, the Branch supports studies testing the efficacy of individual-level and classroom interventions for promoting abstinence and risk-reduction behavior, including condom use and avoidance of concurrent partners, among adolescents and young adults. One effort tested Reach for Health, a school-based intervention that blended community service requirements with a sex education curriculum. The program achieved a significant and long-lasting delay in sexual activity among inner-city middle-school children.
Other activities include providing life skills to young HIV-infected women in Zimbabwe, studying testingamong African-American men, examining how churches respond to HIV, and learning how women and couples balance their desires for children with their desires to avoid HIV infection.
The PDB is the primary source of NICHD support for research in the demographics of HIV, sponsoring studies of the social, demographic, economic, or other structural impacts of HIV/STI in populations. The Branch also sponsors research on the implications of patterns of sexual behavior, geographical mobility, testing, and treatment in a population for the spread of HIV and other STIs.
The need to inform HIV-prevention efforts has been a strong motivator for recent research on the demographics of sexual behavior. Examples of Branch topics of interest include studies on the acceptability of microbicides, the role of religious organizations in HIV prevention, the relationship between individuals' and couples' desires to prevent disease transmission while being able to have the number of children they want, and social networks and HIV prevention.
The MPIDB sponsors research to understand and prevent mother-to-child transmission of HIV. The Branch's portfolio includes research on the acquisition of HIV infection through in utero exposure, intrapartum exposure, and postnatal exposure via breast milk. Its prevention research includes the use of antiretroviral drugs or use of HIV passive or active immunization for prevention of mother-to-child transmission, as well as studies to evaluate optimal ways to implement proven interventions in developing countries.
Since 1990, the MPIDB has contributed to a series of research advances that have drastically reduced rates of mother-to-child transmission of HIV, especially in the United States. In 2011, the MPIDB and the National Institute of Allergy and Infectious Diseases (NIAID) co-funded the NICHD/HPTN 040 clinical trial, which found that a multi-drug regimen given to the newborns of HIV-infected women who had not received antiretrovirals before labor reduced the infants' risk of infection.
Although early diagnosis and treatment during pregnancy is ideal, many HIV-infected pregnant women around the world still do not receive this level of care. This line of research continues with the Promoting Maternal-Infant Survival Everywhere (PROMISE) study, co-funded by the MPIDB and NIAID through their International Maternal, Pediatric, Adolescent AIDS Clinical Trials (IMPAACT) Group. The PROMISE study, begun in 2010, will enroll nearly 8,000 HIV-positive pregnant women and new mothers in 18 nations to compare the safety and efficacy of a variety of methods to prevent mother-to-child transmission.
The MPIDB supports research on the pharmacokinetics/pharmacodynamics and safety of antiretroviral drugs in pregnancy. The Branch also supports research, investigating the impact of HIV infection and antiretroviral therapy on child development, including growth, sexual maturation, metabolism, socialization, neurodevelopment, and neurologic function. It also supports research on drug toxicity in pregnant women and on the effects of antiretroviral drugs on the fetus and infant, especially long-term effects.
An example of the MPIDB's interest in this area is its Pediatric HIV/AIDS Cohort Study (PHACS). In 2012, study researchers found that children who were exposed to HIV in the womb, even if they did not become infected with the virus, were at high risk of a language delay compared with other children. This study, co-funded by seven other NIH Institutes and offices, was established in 2005 to evaluate the long-term safety of fetal and infant exposure to prophylactic antiretroviral drugs and the effects of perinatally acquired HIV infection in adolescents. These results suggest the need for early language interventions for children exposed prenatally to HIV. The Obstetric and Pediatric Pharmacology and Therapeutics Branch also supports research in the area of pediatric and obstetric drugs.
The MPIDB sponsors research on the unique characteristics and impacts of immune function, immune markers, HIV infection, and co-infection in pregnant and other women. Similarly, the CDDB supports research into the effects of female genital biology and sex hormones on the transmission, acquisition, and progression of HIV/AIDS and other STIs.
The MPIDB and several other Branches support the development of prophylactic, diagnostic, and therapeutic strategies for HIV/AIDS that are targeted to the unique biology and social contexts of women, including pregnant women. These strategies may be pharmaceutical, behavioral, nutritional, or in other domains, as relevant to individual branch interests.
Additionally, the MPIDB supports studies evaluating the effects of HIV and its therapies on women throughout the lifespan. For example, the MPIDB co-funds with NIAID the Women's Interagency HIV Study (WIHS), which was established in 1993 to investigate the impact of HIV infection on women in the United States. The WIHS cohort of HIV-infected and HIV-uninfected high risk women has provided critical information on the natural history of HIV infection in women, including predictors of disease progression and death, the prevalence and incidence of genital neoplasia and its relationship to human papillomavirus infection, rates and complications of other co-infections such as hepatitis C virus, response to and complications of highly active antiretroviral therapy, and rates of co-morbidities such as diabetes, cardiovascular disease, and cancers.
The MPIDB supports research on the interactions between hormonal contraceptives and antiretroviral drugs, evaluating both the effect of the antiretroviral drug on the contraceptive and the effect of the contraceptive on antiretroviral drug levels.
Contraception and fertility are other major areas of NICHD's research funding on women and HIV/AIDS. The CDDB supports studies of the safety and efficacy of contraceptives and infertility treatments in HIV-positive women.
The PDB is also involved in studies of contraception and HIV prevention. Its portfolio includes studies of the interrelationships among pregnancy, pregnancy desires, pregnancy prevention, and HIV/STI prevention, plus the development of interventions based on an understanding of these relationships.
The MPIDB sponsors a spectrum of research aimed at understanding the transmission dynamics, course of infection, prevention, and management of HIV in youth. Areas of interest include therapy adherence; development of vaccines and other methods, such as use of pre-exposure prophylaxis, to prevent the spread of infection; and strategies for managing HIV disease and secondary infections.
The PDB is focused on behavioral aspects of HIV/AIDS in adolescents, examining the factors that influence adolescents' propensity for risky behavior and developing and evaluating interventions tailored toward adolescents.
The Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN), funded by the MPIDB, National Institute of Mental Health, and National Institute on Drug Abuse, is an example of NICHD's focus on HIV in adolescents. Through a collaboration with the Centers for Disease Control and Prevention (CDC), the ATN is carrying out the Strategic Multisite Initiative for the Identification, Linkage, and Engagement in Care of Youth with Undiagnosed HIV Infection (SMILE in CARING for YOUTH). Begun in 2009, SMILE in CARING for YOUTH links ATN's research and treatment network with CDC-funded HIV counseling and testing programs for adolescents and young adults at high risk for infection. The program is testing and improving methods to link HIV-infected young people with treatment and improve treatment compliance, and it is providing opportunities for these youths to participate in clinical trials.
The Pediatric HIV/AIDS Cohort Study (PHACS), led by MPIDB in collaboration with eight co-funding Institutes, examines trends in health and behavior of youth who acquired HIV infection in infancy and who are reaching adolescence and young adulthood. PHACS has helped show how these youth with lifelong HIV infection face special challenges for themselves and their partners as they become sexually active (Source: Tassiopoulos, K. et. al. (2013). Clinical Infectious Disease. PMID: 23139252).
The MPIDB is engaged in research to understand and address the unique characteristics of HIV/AIDS and their treatments in children. An example of the MPIDB's interest in this area is its Pediatric HIV/AIDS Cohort Study (PHACS), which found in a 2011 study that hypercholesterolemia is a common side effect of drug therapy in HIV-infected children. The study tracked cholesterol and its treatment in more than 2,500 infected children for 2 years, finding that most children's cholesterol did not decrease over time and that few received drug treatment that could lower their cholesterol. These findings highlight the need for treatment guidelines for hypercholesterolemia in HIV-infected children.
In 2013, NIH-supported researchers reported that a 2-year-old child who was born with HIV and was treated starting in the first few days of life has had her HIV infection go into remissions. This appears to be the first case of a functional cure of HIV.
The MPIDB also funds research related to pediatric diagnosis and monitoring assays and strategies for HIV and associated co-infections, such as tuberculosis, relevant to developing-country settings. An example of MPIDB-funded research in this area is a 2011 study of the pediatric use of the Xpert assay, recommended by the WHO as a test for tuberculosis and drug-resistant tuberculosis in adults. The study found that Xpert provides consistent, accurate, fast results in children, and thus opened this new avenue for diagnosis and care of HIV-infected children's opportunistic infections. (Source: Nicol, M. P., et al. (2011). The Lancet Infectious Diseases. PMID: 21764384)
In addition to funding individual research studies, the MPIDB provides support to the NIAID-funded International Epidemiologic Databases to Evaluate AIDS (IeDEA) to include children in its cohorts. IeDEA's mission is to combine data from multiple research cohorts around the world to examine specific questions about HIV/AIDS that require large data sets.
A large portion of the portfolio of the MPIDB's supports the identification and evaluation of therapies for HIV-infected children, youth, and pregnant women, including treatment and prevention of co-occurring infections and other complications of HIV infection and antiretroviral therapy. The Branch is also involved in the development of vaccines and other methods for the prevention of HIV transmission among adolescents and between mother and child.
The MPIDB ATN, the NICHD Domestic and International Pediatric and Maternal HIV Clinical Trials Network, and the co-funded NICHD and NIAID International Maternal, Pediatric, Adolescent AIDS Clinical Trials (IMPAACT) Group are heavily involved in this area. In 2012, ATN and IMPAACT Group researchers published the finding that vitamin D may improve bone health in adolescents on the common anti-HIV drug tenofovir. Due to hormonal effects of tenofovir therapy, bone density loss is a common side effect. This discovery may provide a low-cost method to increase the long-term health and well-being of HIV-positive youth.
The NICHD-NIAID co-funded IMPAACT Group research has also had several breakthroughs in treating HIV-infected infants. A study published in 2010 showed that initial therapy with a three-drug regimen, including the protease inhibitor lopinavir/ritonavir, was more effective than a three-drug regimen containing nevirapine for treating infants who became infected despite being exposed to nevirapine at birth. (Source: Palumbo, P., et al. (2010). New England Journal of Medicine. PMID: 20942667). These findings led to changes in the WHO treatment guidelines, Antiretroviral therapy for HIV infection in infants and children: towards universal access - recommendations for a public health approach, 2010 revision (PDF - 1.9 MB). Later in 2010, the IMPAACT group reported that a protease-inhibitor lopinavir/ritonavir-based therapy was more effective for treating HIV-infected infants than was a nevirapine-based therapy even when the infected child had not been exposed to nevirapine at birth (Source: Violari, A. et. al. (2012). New England Journal of Medicine. PMID: 22716976).
In addition to the MPIDB, the CDDB funds the development and evaluation of anti-HIV spermicidal microbicides as part of its contraception research.
The PROMISE (Promoting Maternal-Infant Survival Everywhere) study, co-funded by the MPIDB and NIAID through their IMPAACT, is evaluating two different strategies to allow safer breastfeeding in developing countries for 12 months or longer–comparing infant or maternal antiretroviral drug administration during breastfeeding to prevent HIV transmission through breast milk.
The Pediatric Growth and Nutrition Branch (PGNB) supports research and research training in nutritional science, childhood antecedents of adult disease, developmental endocrinology, developmental neuroendocrinology, and physical growth and body composition. One major focus of the Branch's research support is global health and nutrition, particularly the role of nutrition in the prevention, care, and treatment of HIV/AIDS. It also supports research on the effect of HIV on the immune function of the gut.
Proper feeding of infants exposed to HIV infection is a great concern in developing nations. Current policies call for early exclusive breastfeeding followed by rapid weaning to limit exposure to HIV. PGNB-supported investigators have developed a method to reduce transmission by heat-treating expressed milk. The process produced minimal changes in breast milk composition and was successfully implemented in rural settings where HIV prevalence is high. This work represents the importance of translational science in providing infants with a safe source of nutrition.
One of the great successes in HIV research has been the development of highly effective interventions to prevent MTCT (PMTCT).
Clinical trials have identified simple, less expensive, effective prevention strategies that are feasible for resource-limited settings, including interventions to reduce HIV transmission through breastfeeding.
Although great strides have been made in implementing PMTCT programs in low- and middle-income countries, there remain significant bottlenecks and challenges in developing and carrying out PMTCT programs in these settings. Implementation science projects examine and develop new ways to improve how we put into practice the PMTCT interventions that we already know will work.
In 2012, the MPIDB, with co-funding from the President's Emergency Fund for AIDS Relief (PEPFAR), funded nine grants to assess optimal ways to implement PMTCT interventions in developing countries. MPIDB is working with the Fogarty International Center to bring these international researchers together with developing country implementers and public health professionals to share information about the studies and facilitate rapid implementation of successful projects. Read more about the Implementation Science Project.
Both the PDB and the MPIDB are involved in building research capacity in HIV/AIDS through training and infrastructure development in the African, Asian, and Latin American nations most affected by the disease.
Investigators with the MPIDB-funded NICHD International Site Development Initiative (NISDI) identified distinct viral load thresholds in children receiving therapy that identify children at increased risk of developing HIV-related clinical illnesses despite treatment (Source: Siberry, G. K. et. al. (2012). Journal of Acquired Immune Deficiency Syndrome. PMID: 22343177).
A separate study by NISDI Brazilian scientists evaluated adherence to antiretroviral therapy during pregnancy and postpartum, finding that adherence to treatment significantly decreased after delivery, indicating a need for additional support to women postpartum (Source: Kreitchmann, R. et. al. (2012). AIDS Patient Care STDs. PMID: 22663185).
To achieve its goals for HIV/AIDS research, the NICHD supports a variety of other activities related to this disease. Some of these activities are managed through the components listed above; others are part of NIH-wide or collaborative efforts in which the NICHD participates. Some of these are listed below.
- The Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) conducts research on methods to improve the health and well-being of HIV-infected and at-risk young people, including studies of medicines and strategies to prevent and treat HIV infection, among other related topics.
- The Centers for AIDS Research provide administrative and shared research support to enhance and coordinate high-quality AIDS research projects. The centers provide core facilities and emphasize the importance of interdisciplinary collaboration in AIDS research.
- The Contraceptive Clinical Trials Network (CCTN) includes 12 research sites studying contraceptive methods and devices for women and two sites for men. It focuses on preventing HIV and other sexually transmitted infections.
- The NICHD Domestic and International Pediatric and Maternal HIV Clinical Studies Network conducts domestic and international clinical trials of treatment for HIV and associated co-infections, as well as complications of HIV and its treatment in pregnant women, infants, children, and adolescents, and prevention of mother-to-child HIV transmission.
- The International Epidemiologic Databases to Evaluate AIDS (IeDEA) consortium consists of regional sites collecting and defining key variables, harmonizing data, and implementing methodology to generate large data sets in order to address high-priority research questions and streamline HIV/AIDS research. NICHD funds the pediatric component of IeDEA.
- The International Maternal, Pediatric, Adolescent AIDS Clinical Trials (IMPAACT) Group conducts clinical trials in collaboration with the NICHD Network and develops and tests methods to prevent HIV transmission and treat HIV infection in pregnant women, infants, children, and teens.
- The National Longitudinal Study of Adolescent Health (Add Health) is a longitudinal effort to examine a nationally representative sample of adolescents' and young adults' social contexts- including families, friends, peers, schools, neighborhoods, and communities- and their effects on their health and risk behaviors.
- The Obstetric-Fetal Pharmacology Research Unit (OPRU) Network supports research units with pharmacological, clinical, and basic components in an effort to advance testing of therapeutic drugs during pregnancy.
- Through the Global Partnerships for Social Science and Behavioral Research on HIV/AIDS program, the NICHD and two other NIH Institutes have funded 10 partnerships of U.S.-based and African institutions to increase research capacity at the African institution. The second round of partnerships has expanded to institutions in Asia and Russia.
- The Pediatric HIV/AIDS Cohort Study (PHACS) network studies the long-term safety of anti-HIV drugs in fetuses and infants and the impact of HIV infection and treatment on children and teens who became infected before, during, or shortly after birth.
- The Women's Interagency HIV Study (WIHS), the largest and longest ongoing U.S. study of HIV infected women, studies the unique ways HIV/AIDS and HIV treatments affect women, the relationships between HIV/AIDS and other diseases in women, and the impact of hormones on HIV disease.
- In addition, staff in the MPIDB are active in the following HIV/AIDS-related activities:
- The NICHD AIDS Coordinating Committee (managed by the Office of Global Health Research).
- Branch staff are involved in several President's Emergency Plan for AIDS Relief (PEPFAR) committees, including the PEPFAR Prevention of Mother-to-Child Transmission/Pediatric Working Group, the PEPFAR Tuberculosis Working Group, the PEPFAR Public Health Evaluation Subgroup, and the Public-Private Partnership for Pediatric Antiretroviral Drugs Group.
- Branch staff are involved as consultants with the WHO in their development of guidelines for treatment of HIV-infected children and prevention of mother-to-child transmission in developing countries.
- The Department of Health and Human Services (DHHS) Panel on Pediatric Antiretroviral Therapy and Management Guidelines, the HHS Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, and the HHS Guidelines for Treatment and Prevention of Opportunistic Infection in HIV-Exposed and Infected Children. The MPIDB staff serve as Executive Secretary to these panels that develop HIV and co-infect treatment guidelines for children and prevention of mother-to-child transmission for the United States. Additionally, two staff serve as members to the HHS Panel on Antiretroviral Therapy in Adults and Adolescents.
- MPIDB staff involvement with NIH Office of AIDS Research (OAR) committees includes the Therapeutics Research Planning Committee, the Natural History and Epidemiology Research Planning Committee, the Etiology and Pathogenesis Research Planning Committee, the Microbicides Research Planning Committee, the social and behavioral science planning committee, the International Research Planning Committee, the Racial and Ethnic Minority Committee, the Women and Girls Committee, the Training, Infrastructure, and Capacity Building Committee, and the Vaccine Research Planning Committee. Staff are also involved with Indo-U.S. and Russia-U.S. joint working groups on HIV/AIDS research.
- Subgroup on Childhood Tuberculosis (TB) of the DOTS Expansion Working Group of the Global Stop TB Partnership. MPIDB staff serve as a consultant and member of the sub-group.
- Centers for Disease Control and Prevention Elimination of Pediatric HIV in U.S. Stakeholders Group: MPIDB staff are members of this group evaluating ways to eliminate new pediatric HIV infection in the United States.
- American Academy of Pediatrics Committee on Pediatric AIDS and American College of Obstetrics and Gynecology HIV Expert Work Group: MPIDB staff are members of these professional society committees that deal with HIV in children and women.