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.