What is Human Immunodeficiency Virus (HIV)?

Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immune deficiency syndrome (AIDS), a disease characterized by progressive deterioration of the immune system. The diminished immune function of HIV/AIDS patients puts them at risk for opportunistic infections, which may lead to death.

Global Burden

Human Immunodeficiency Virus (HIV)

HIV/AIDS is a global epidemic. There are currently an estimated 34 million people infected with the virus, including 3.4 million children under the age of 15.1 Although HIV is prevalent worldwide, sub-Saharan Africa bears the greatest burden of disease. Nearly two-thirds of people living with HIV/AIDS are located in this region; in some countries prevalence exceeds 30% of the adult population. South and Southeast Asia are second to Africa in terms of the total number of individuals infected. Eastern Europe and Central Asia show a disturbing trend of increasing incidence over the past decade, whereas infection rates in many other regions have plateaued or begun to decline.2

  Number of people living with HIV (% population) New HIV infections, annually Deaths due to AIDS
Sub-Saharan Africa 22.9 million (5.0%) 1.9 million 1.2 million
Middle East and North Africa 470,000 (0.2%) 59,000 35,000
South and Southeast Asia 4 million (0.3%) 270,000 250,000
East Asia 790,000 (0.1%) 160,000 90,000
Caribbean 200,000 (0.9%) 12,000 9,000
Eastern Europe and Central Asia 1.5 million (0.9%) 160,000 90,000
Western Europe and Central Europe 840,000 (0.2%) 30,000 9,900
North America 1.3 million (0.6%) 58,000 20,000
Latin America 1.5 million (0.4%) 100,000 67,000
Oceania 54,000 (0.3%) 3,300 1,600
Total: 34 million (0.8%) 2.7 million 1.8 million

Encouragingly, the overall number of new HIV infections has fallen 21% since 1997, when incidence is thought to have peaked.2 Yet the pandemic is far from over. In 2010, approximately 2.7 million people contracted the virus and there were about 1.8 million AIDS-related deaths.1 Young people between the ages of 15 and 24 now account for almost half of all new infections. Young women are especially vulnerable, with prevalence rates up to eight times greater than those of young men.2

The economic burden of HIV/AIDS is extreme due to the impact of the virus on young people. Disability or death of the working and parenting population leads to devastating effects on household income, as well as decreased productivity and impaired growth at the national level. The epidemic is estimated to cause a 1.5% annual loss in gross domestic product (GDP) each year in the countries worst affected by HIV/AIDS.3 Societal resources of already poor nations are further strained by the more than 16 million orphans who have lost their parents to AIDS.2 These factors combine to create downward spirals of poverty and social disruption in regions severely affected by HIV/AIDS.

Causative Agent

hiv

HIV is a member of the genus Lentivirus within the Retroviridae family. The virus infects immune cells, such as T cells, which bear the surface molecule CD4. After entry into a permissive cell, a viral enzyme termed reverse transcriptase converts the RNA genome into double stranded DNA. This DNA becomes integrated into the cellular genome by another HIV enzyme, called integrase. Once integrated, the HIV provirus takes advantage of host cell enzymes to transcribe and translate its genetic material into the viral proteins, which assemble into new viral particles and bud from the infected cell.

HIV mutates rapidly, and today patients are infected by many different strains. Most broadly, HIV can be classified as HIV-1 or HIV-2. HIV-1 is more virulent than HIV-2, and causes the majority of infections. HIV-1 can be divided into several distinct groups, which are themselves divided into subtypes, or clades, that display distinct geographic infection patterns. Treatment is more complicated in regions where more than one clade is circulating because hybrid strains can arise. The extreme diversity of HIV strains presents one of the most important hurdles to the development of new biomedical prevention tools, and to successful treatment programs.

Transmission of HIV occurs through exposure to infected body fluids including blood, semen, vaginal secretions, and breast milk. The major routes of infection are by sexual contact, through contaminated needles, and from infected mother to child in utero, at birth, or through breastfeeding.

Pathogenesis

HIV primarily infects CD4+ T cells. Infection of these cells leads to destruction of this subset of immune cells, weakening the body’s defenses. AIDS is characterized by a CD4+ lymphocyte count of <200 cells/µL. Once a patient develops AIDS, they become extremely susceptibility to opportunistic infections.

HIV can infect other immune cells, such as macrophages, which may serve as both a reservoir of virus and means of viral spread to other body tissues.

Diagnosing HIV can be difficult because the disease cannot be diagnosed through clinical symptoms. Two to four weeks after infection, patients may display flu-like symptoms accompanied by a rash and fever. However, many patients are initially asymptomatic. Although the incubation period between infection and onset of AIDS is often cited as seven to 10 years, disease course can be accelerated in low- and middle-income countries due to environmental factors, co-morbidities, and poor nutrition.

Current Control Strategy

There is no vaccine to prevent HIV infection, and available antiretroviral drugs do not provide a cure. Risk-reducing behaviors are therefore important to preventing HIV infection. The U.S. Centers for Disease Control and Prevention (CDC) recommends that everyone between the ages of 13 and 64 be tested for HIV at least once, with annual testing for those at increased risk.4 For pregnant women who are infected with the virus, antiretroviral therapies are available to limit the chances of transmission to the baby. Sexual transmission of HIV can be reduced by consistent and correct use of latex condoms, limiting the number of sexual partners, or abstaining from sexual activity all together. One of the most effective biomedical strategies to prevent HIV, medical male circumcision, has been recognized by the WHO, UNAIDS and other major health organizations as a key component of the global strategy to end the HIV/AIDS epidemic. Clinical trials have shown that medical male circumcision, which entails the surgical removal of the foreskin, can reduce a man’s risk of acquiring HIV from his female sexual partner by at least 60 percent.5

In November 2010, the results from a clinical trial showed promise for a new HIV prevention strategy called pre-exposure prophylaxis or PrEP. PrEP involves HIV-negative people at risk for HIV using antiretroviral drugs (ARV) to reduce the risk of HIV infection. ARV drugs are currently used by HIV-positive people to stay healthy. The trial, iPrex, demonstrated that daily use of Truvada (a combination ARV composed of tenofovir disoproxyl fumarate and emtricitabine) reduced the risk of HIV by 44 percent among men who have sex with men. PrEP is not yet recommended for use, but the CDC issues interim guidance of PrEP as an HIV prevention strategy for men who have sex with men since Truvada is already licensed and there is a potential for immediate, off-label use.

Other trials are investigating a similar approach to HIV prevention, in which an HIV-positive person is treated with ARVs to reduce the likelihood of infecting a partner during sex. In 2011, one trial carried out in nine countries across Africa, Asia, and South America demonstrated that treating an HIV-positive person with ARVs successfully decreases the amount of virus present in their bodies, thus reducing the rate of HIV transmission during sexual intercourse by 96%.6 While this strategy, called “treatment as prevention,” could reduce the rate of new infections in some settings, there are many remaining challenges and questions that hope to be answered through additional data analysis and clinical trials.

Another type of innovative HIV-prevention tool in development is microbicides. Microbicides are biomedical products being designed as vaginal products to protect healthy women from becoming infected, and as rectal products that both men and women could use. These products are being tested in multiple forms, such as vaginal and rectal gels used around the time of sex, and as vaginal rings, which would slowly release the microbicide drug to provide preventative coverage for up to one month.

Intravenous injection of illicit drugs also presents a considerable risk for infection. If drug use cannot be stopped through counseling and treatment, injection drug users should only use clean needles to reduce their risk of infection. Finally, post-exposure prophylactic treatment with ARV-based drugs can sometimes prevent infection if administered quickly.

Existing Products

Drugs

The standard of care for HIV is combination antiretroviral therapy (ART) as well as the management and treatment of opportunistic infections that may result from HIV-related immune suppression. The ARV strategy most widely used is called Highly Active Antiretroviral Therapy (HAART) and consists of combination treatment with two nucleoside reverse transcriptase inhibitors (NRTIs) co-administered with a third drug with a different mechanism of action, such as a nonnucleoside reverse transcriptase inhibitor (NNRTI), a protease inhibitor, or an integrase inhibitor. There are currently 35 HIV products approved by the U.S. Food & Drug Administration (FDA) including individual drugs and fixed dose combinations.7

The first once-a-day, multi-class, fixed dose formulation for the treatment of HIV was approved by the FDA in July 2006.7 Atripla contains two NRTIs (tenofovir disoproxil fumarate and emtricitabine) developed by Gilead Sciences, Inc. and one NNRTI (efavirenz) developed by Bristol-Myers Squibb. In order to make this easy-to-use formulation as well as other HIV treatments available to HIV patients in need, Gilead has developed a tiered pricing system for countries based on gross national income. They have also entered into non-exclusive licensing agreements with 13 generics manufacturers in India to produce high quality generic products.

Improving access to ARVs in low and middle income countries is a key priority. As of December 2009, 36% (5.2 million) of the 15 million people living in low- and middle-income countries requiring treatment were receiving antiretroviral therapy.2

Low- and Middle-Income Country Regions Number of People Receiving ARVs Number of People Needing ARVs Antiretroviral Therapy Coverage
Sub-Saharan Africa 3.9 million 10.6 million 37%
Latin America and Caribbean 478,000 950,000 50%
East, South, and South-East Asia 739,000 2.4 million 31%
Europe and Central Africa 114,000 610,000 19%
North Africa and Middle East 12,000 100,000 11%
Total: 5.3 million 14.6 million 36%

Vaccines

There are no vaccines for the prevention of HIV infection.

Diagnostics

Diagnostics for HIV are used for:

  • Identification of infection
  • Determining eligibility for treatment and monitoring disease progression monitoring disease progression (CD4+ T cell counts)
  • Monitoring treatment efficacy/potential treatment failure (viral load testing)

Diagnosis of HIV is not taken lightly. Generally diagnosis occurs in two stages. First, a screening or first-line test is used for presumptive diagnosis based on the presence of antibodies. Screening tests generally have very high sensitivity but may have lower specificity. Patients with a positive screening test then receive a supplemental or confirmatory test that has higher specificity to confirm that the positive result in the screening test is due to HIV infection.

Screening tests for HIV are primarily immune-based. Enzyme-Linked Immunosorbent Assays (ELISAs) are the most commonly used laboratory diagnostic for HIV. The latest ELISA assays detect both antibodies and viral antigens in blood samples and are used in both patient diagnosis and screening of blood donations and other blood products. Simplified, instrument-free, immune-based assays are also available for rapid HIV screening in settings without access to laboratory facilities. More than 25 commercially available rapid tests for HIV screening have been independently evaluated by the WHO and many have demonstrated acceptable sensitivity, specificity, and suitability for use in resource poor settings.9

Confirmatory diagnosis can be performed using western blot, line immunoassays, or — for high prevalence areas — the more sensitive and specific ELISA test is performed using a minimum of two to three different rapid assays. The choice of confirmatory test is informed by HIV prevalence in the patient population as well as by cost and the availability of laboratory services.

Decreases in the CD4+ T lymphocyte cell population are indicative of progression of HIV to AIDS. As many HIV drugs result in toxicities from long-term use, the WHO uses CD4+ cell counts in parallel with clinical staging to determine when antiretroviral (ARV) therapy should be initiated. Monitoring CD4+ counts is not trivial. CD4+ counts generally require expensive flow cytometry equipment and highly trained laboratory personal. Although simplified bench top devices are available (e.g., FACSCount, BD; Guava EasyCD4; Partec Cyflow; PointCARE), most of these machines still cost over US$20,000, require regular electricity, and are potentially expensive to repair and maintain, largely limiting their utility to centralized laboratory facilities in the developing world.10

Viral load is the most sensitive method to monitor for ARV treatment failure. The majority of tests today monitor viral load by using nucleic acid amplification techniques to detect the presence of viral nucleic acid.11 Treatment failure occurs when viral load does not drop, or repeatedly rises after have dropped previously, in what is called virologic failure.12 Nucleic acid amplification-based diagnostics require expensive laboratory equipment and highly trained personnel, making their widespread implementation in low-resource settings very difficult.

References

  1. UANIDS (2011) World AIDS Day Report.
  2. UNAIDS (2010) Global Report: UNAIDS report on the global AIDS epidemic.
  3. Greener R. et al (November 2004), 'The Impact of HIV/AIDS on Poverty and Inequality' in 'The Macroeconomics of AIDS'.
  4. CDC, Basic Information about HIV and AIDS.
  5. Wawer M, Kigozi G, Serwadda D, et al. Trial of Male Circumcision in HIV+ Men, Rakai, Uganda: Effects in HIV+ Men and in Women Partners. 15th Conference on Retroviruses and Opportunistic Infections, Boston, MA, USA, February 3-6, 2008.
  6. Cohen M. S., Chen Y.Q., McCauley M et. al. Prevention of HIV-1 Infection with Early Antiretroviral Therapy. N Engl J Med 2011; 365:493-505.
  7. FDA, Antiretroviral drugs used for the treatment of HIV.
  8. WHO, UNICEF, UNAIDS (2010) Towards universal access: Scaling up priority HIV/AIDS interventions in the health sectorData table also available here.
  9. WHO (2009) HIV Assays:  Operational Characteristics (Report 16: Rapid Assay)See Annex 2 for WHO evaluation results for products that are currently commercially available.
  10. WHO (2007) Laboratory Guidelines for Enumerating CD4 T Lymphocytes in the Context of HIV/AIDS.
  11. Best SJ, Gust AP, Johnson EI, McGavin CH, Dax EM. Quality of Human Immunodeficiency Virus Viral Load Testing in AustraliaJournal of Clinical Microbiology; 2000 November; 38(11): 4015–4020.
  12. 12. AidsInfo.gov (2009) HIV Treatment Failure.

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Drugs

Analysis

Drug development for HIV is primarily focused on:

  1. Reformulation of current ARVs to improve access and ease of use, especially for neglected populations
  2. Developing microbicides to reduce transmission of HIV, especially to women

Although access to ARVs is improving in the developing world, there are two groups of people living in resource poor settings that remain extremely neglected in terms of access: those living in rural areas with poor infrastructure, and children.1,2,3

People living in rural areas have reduced access to HIV medications primarily due to (1) limited access to key supportive technologies needed for successful HIV treatment and monitoring, (2) limited stability and quality control for drugs stored in extreme environmental conditions, (3) need for simplified drug treatment regimens to improve adherence and ease of use, and (4) improved safety profiles of medications that allow use in patients with minimal medical supervision.

Despite making up more than 14% of all new HIV infections, only 28% of children who need anti-retroviral treatment receive it.2 Children have reduced access to HIV medications primarily due to (1) a limited ability to accurately diagnose HIV in very young children, (2) a lack of information on the efficacy and appropriate dosing of HIV medications for children, and (3) a lack of appropriate pediatric formulations. Access considerations will benefit from additional product development programs, however specific descriptions of this work is beyond the scope of this Primer.

Microbicides

Analysis

Beyond improving access, the development of topical microbicides to prevent the transmission of the HIV virus is a focus for HIV drug development. Although microbicides are not drugs in the traditional sense, many contain active ingredients that overlap with drugs that are currently in use to treat HIV. Microbicides have gained attention as a potential tool to reduce HIV transmission and, perhaps more importantly, as a potential tool to empower women to protect themselves from transmission.

Women in resource-poor settings are often limited in their ability to require their sexual partners to use condoms due to high rates of sexual violence, a high prevalence of polygamy, and other issues of gender inequality. Microbicides offer a discreet method for women who are otherwise vulnerable to infection by their partner to protect themselves.

Microbicide development thus far has faced mixed success. Early programs focused on using general anti-microbial agents, such as buffers, surfactants, polyanionic solutions, and other non-drug containing materials. After several failures in phase II/III trials,4 programs now focus on developing microbicides that contain antiretroviral-based drugs, which are used to treat HIV, including the reverse transcriptase inhibitors dipivirine and tenofovir. Overall, Microbicide products appear to be more promising but raise new questions such as the risk for accelerating therapeutic drug resistance.

Positive results were announced in July 2010 from the CAPRISA 004 Phase IIb microbicide trial of 1% tenofovir gel, which was tested in 889 South African women. The trial results indicated that 39% fewer infections occurred among women who received 1% tenfovir gel compared to women who did not receive the gel.5 While these results were promising, additional data is needed to verify whether 1% tenofovir gel is truly effective at preventing HIV infection among women.

 StrengthsWeaknessesOpportunitiesRisks
Microbicides (Drug containing)
Most advanced program: Tenofovir gel, Phase III Additional product in Phase I and II stage of developmentActive ingredients have known antiviral activity for HIVDrug-containing products more expensiveAdherence Prevention of HIV in womenPotential to accelerate resistance to drugs used for HIV treatment

Vaccines

Analysis

After 15 years of research and development, the first glimmer of hope for HIV vaccine success came with the publication of the RV 144 vaccine trial results from Thailand in December 2009. More than 16,000 patients were registered for the trial to receive a series of priming vaccinations with a canarypox-based viral vector vaccine expressing the HIV env, gag, and pro genes (ALVAC-HIV vCP1521, Sanofi Pasteur) followed by boosters with a recombinant protein vaccine containing subunits of the HIV surface glycoprotein gp120 (AIDSVAX B/E, VaxGen). The study showed approximately 30% protection against HIV infection as compared to the placebo control group.6

Several unanswered questions remain following this study:

  1. What is the immunological basis of protection in those people who received the vaccine and did not become infected?
  2. In those who were protected, how long will that protection last?
  3. In those who were vaccinated but infected with HIV, will the progression of disease be different?
  4. If the vaccine is evaluated in a higher risk population (i.e., intravenous drug users, sex workers, or men who have sex with men) would the same level of protection be observed?

Studies are now ongoing to try to understand the mechanism of immunity in the protected group using samples collected from patients throughout the trial and to monitor those patients who become infected during the trial to look for impacts of vaccination on disease severity. Long-term follow up of all of the uninfected patients from the RV 144 trial as well as additional trials to evaluate these vaccines in higher risk populations would also be valuable, but extremely expensive, and are not planned at this point in time.

The use of a heterologous prime-boost strategy, as was done in the RV 144 trial in Thailand, is the predominant strategy employed in other vaccines currently in clinical development for HIV. The rationale for this approach is that combinations of vaccines based on different technologies and antigens will provide a more comprehensive immune response. This strategy may have arisen in part due to the failure of the AIDSVAX B/E vaccine in a phase III clinical trial when the vaccine was evaluated alone in intravenous drug users.5 Beyond the viral vector-recombinant protein prime-boost strategy, DNA-viral vector, and viral vector-viral vector combinations are also in clinical development.

In addition to preventive vaccines, several vaccines are now in development as therapeutic vaccines or adjuncts to ARV therapy in patients who are already HIV positive. Clinical trial data are not yet available for these studies.

As the vaccine pipeline for HIV is quite large, the pipeline presented here is largely limited to clinical stage programs. Only select pre-clinical and discovery phase programs are included.

 StrengthsWeaknessesOpportunitiesRisks
Viral vector
Most advanced program: ALVAC-HIV, vCP1521 (Preventive, prime for use with AIDSVAX boost), Phase III Additional products at every stage of developmentDemonstrated clinical efficacy (~30% protection) in phase III in combination with AIDSVAX Multiple viral vectors are in clinical development (e.g. canarypox, modified vaccinia ankara (MVA), fowlpox, adenovirus)Only partial protection observed for canarypox-based virus in phase III and duration of protection may be limitedNew prime-boost combinations with other clinical stage vaccines More extensive clinical trials in high risk populations Studies to evaluate potential as adjunct to therapy or to reduction in disease severity in those who are or become HIV positiveThere are no FDA approved viral vector vaccines on market Termination of adenovirus-based HIV vaccine trial in 2005 raised safety concerns which may lead to increased regulatory scrutiny Mechanism of protection not fully understood
Recombinant/purified protein
Most advanced program:  AIDSVAX B/E (Preventive, boost following ALVAC-HIV primer), Phase III Additional products in phase I and II developmentBased on well accepted strategy for vaccine development Demonstrated clinical efficacy (~30% protection) in phase III in combination with ALVAC-HIVAIDVAX failed to show efficacy in a clinical trial among intravenous drug users when used aloneThere are multiple FDA approved vaccines based on recombinant protein technology New prime-boost combinations with other clinical stage vaccines More extensive clinical trials in high risk populations  Studies to evaluate potential as adjunct to therapy or to reduction in disease severity in those who are or become HIV positiveMechanism of protection not fully understood
Peptide
Most advanced program:  LIPO-5 (Preventive) and Vacc-4x (Therapeutic), Phase IIDemonstrated safety in phase I and phase II trials Vacc-4x phase II trials showed HIV positive patients receiving the vaccine could remain off ARV therapy for several years Potentially inexpensive to produceNo placebo controlled efficacy studies have been conducted yet so difficult to judge potentialNew prime-boost combinations with other clinical stage vaccinesPeptides may have reduced immunogenicity relative to other vaccine technologies, but this remains to be determined
DNA
program:  VRC-HIVDNA016-00-VP, pGA2/JS7, pHIS-HIV-AE, DNA-C, and HIVIS 03 DNA (primarily being evaluated as prime for prime-boost combinations), Phase II Additional products in phase I development Variety of DNA vectors and antigens in development No placebo controlled efficacy studies have been conducted yet so difficult to judge potential New prime-boost combinations with other clinical stage vaccines There are no FDA approved DNA vaccines on market

Diagnostics

Analysis

Three key areas of need for new HIV diagnostics are:

  • Rapid point-of-care pediatric diagnostics for infant screening that avoid interference with maternal antibodies
  • Simple handheld devices that provide rapid and accurate CD4+ counts to determine when ARV treatment should be initiated.  (There are several products in early stage development to assess CD4+ counts at the point of care or in peripheral laboratories.)
  • Simple handheld devices that provide rapid and accurate viral load testing to monitor for treatment failure in patients on ARV therapy

References

  1. Castelli F et al. (2010) “Antiretroviral (ARV) therapy in resource poor countries: what do we need in real life?” The Open AIDS Journal 4: 28-32.
  2. UNAIDS (2010) Global Report: UNAIDS report on the global AIDS epidemic.
  3. Volberding PA and Deeks SG (2010) “Antiretroviral therapy and management of HIV infection.” The Lancet376:  49-62.
  4. McGowan I (2010) “Microbicides for HIV prevention:  reality or hope?” Current Opinion in Infectious Diseases23:  26-31.
  5. Karim Q.A., Karim S.S.A., Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women. Science 329( 5996): 1168-1174.
  6. Rerks-Ngarm S et al. (2009) “Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand.” The New England Journal of Medicine361:  2209-2220.

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The following series of tables describe the availability of tools for research, discovery, and development of novel drugs, vaccines, and diagnostics for HIV. The tools listed in the following tables are not intended to be an all-inclusive list but rather capture the most common tools used for drug, vaccine, and diagnostic development. The tools for HIV are generally well developed.

Drugs Development Tools

Basic Research: Target IdentificationTarget ValidationScreening: Hit/Lead Identification OptimizationPre-clinical ValidationClinical Validation

Genome: Sequenced 

Key databases: Los Alamos National Labs HIV Databases 

In vitro culture: Yes, laboratory strains and primary isolates; infectious molecular clones are available

Gene knock-outs: Yes, using infectious clones 

Conditional gene knock-outs: Yes, temperature sensitive mutants

Transposon mutagenesis: Yes 

RNAi: Yes 

Other antisense technology:  Yes

Viability assays: Yes, HIV infection causes syncytia formation and cell lysis in culture

Transcription microarrays: Yes, or infected cells 

Proteomics: Yes, the viral proteins are all known 

Crystal structures: Yes

Whole-cell screening assays: Yes, e.g., reporter cell lines 

Enzymatic screening assays:  Yes, e.g., protease assay, reverse transcriptase assay

Animal models:  Yes, chimpanzees are infectable with HIV, but generally do not develop AIDS; non-human primates (e.g., Rhesus macaques) infected with simian immunodeficiency virus (SIV) or SIV/HIV (SHIV) chimeras; only SIV recapitulates AIDS pathogenesis Immunodeficient mice transplanted with human tissues

Monitoring treatment efficacy:Yes, viral load

Availability of endpoints: Yes, plasma viral RNA levels

Availability of surrogate endpoints: Yes, CD4+ T cell count is common secondary endpoint 

Access to clinical trial patients/sites: Yes

Vaccines Development Tools

Basic Research: Antigen IdentificationImmune Response CharacterizationClinical Validation

See drug development tools above

Predictive animal models:  Non-human primates, but predictive capacity is unclear 

Detection of endogenous antigen specific response in clinical samples:Yes, but generally strain-specific and do not lead to virus eradication; broadly-reactive neutralizing antibodies have been detected in a limited number of HIV-positive individuals with chronic infection

Natural immunity well characterized:  No, HIV-positive individuals are unable to clear the infection, although some spontaneously control viral replication to very low levels; potent T-cell responses in long-term non-progressors to AIDS suggest cellular immunity is important

Surrogate markers of protection:  No, immune correlates of protection unknown; potential for vaccine to reduce disease severity or transmission rather than induce sterilizing immunity

Challenge studies possible:  No

Diagnostics Development Tools

Basic Research: Biomarker IdentificationBiomarker ValidationClinical Validation

See drug development tools above

Biomarkers known:  Yes, viral RNA and proteins 

Access to clinical samples:  Yes 

Possible sample types: Serum, plasma, PBMCs

Access to clinical trial patients/sites:  Yes 

Treatment available if diagnosed:  Yes, highly active antiretroviral therapy (HAART)

 

References

Get Involved

To learn how you can get involved in neglected disease drug, vaccine or diagnostic research and development, or to provide updates, changes, or corrections to the Global Health Primer website, please view our FAQs.