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The Centers for Disease Control and Prevention (CDC) recommends HIV testing for all pregnant women as a part of routine prenatal care. The test is usually performed in the first trimester of pregnancy with other routine laboratory tests. HIV testing is recommended because HIV-infected women who do not receive testing are more likely to transmit the infection to their children.
HIV testing may be offered to pregnant women on an "opt-in" or an "opt-out" basis. In the "opt-in" model, women are counseled on HIV testing and elect to receive the test by signing a consent form. In the "opt-out" model, the HIV test is automatically performed with other routine prenatal tests. If a woman does not want to be tested for HIV, she must specifically refuse the test and sign a form declining testing. The CDC recommends "opt-out" testing for all pregnant women because it improves disease detection and treatment and helps reduce transmission to children.
If a woman chooses to decline testing, she will not receive the test. However, she will continue to receive HIV counseling throughout the pregnancy so that she may be as informed as possible about the disease and its impact. She will be offered HIV testing at all stages of her pregnancy in case she changes her mind.
HIV testing begins with a screening test. The most common screening test is the rapid HIV antibody test which tests for HIV antibodies in blood, urine, or oral fluid. HIV antibodies are only produced if an individual is infected with the disease. Therefore, presence of the antibodies is indicative of an HIV infection. Sometimes, however, a person may be infected with HIV but the body has not produced enough antibodies to be detected by the test. If a woman has risk factors for HIV infection but tests negative on the initial screening test, she should be retested in 3 months to confirm that she does not have HIV. Another screening test that is more specific is the HIV antigen/antibody test. This is a newer blood test that can detect HIV infection quicker than the antibody test because it detects both virus particles and antibodies in the blood.
Any woman who has a positive HIV screening test must receive follow-up testing to confirm the diagnosis. The follow-up test can differentiate HIV-1 from HIV-2 and is a more specific antibody test. It may also detect the virus directly in the bloodstream.
Most people infected with HIV develop specific antibodies (i.e. seroconvert) within three to twelve weeks of the initial infection. Diagnosis of primary HIV before seroconversion is done by measuring HIV-RNA or p24 antigen. Positive results obtained by antibody or PCR testing are confirmed either by a different antibody or by PCR.
Antibody tests in children younger than 18 months are typically inaccurate due to the continued presence of maternal antibodies. Thus HIV infection can only be diagnosed by PCR testing for HIV RNA or DNA, or via testing for the p24 antigen. Much of the world lacks access to reliable PCR testing and many places simply wait until either symptoms develop or the child is old enough for accurate antibody testing. In sub-Saharan Africa as of 2007–2009 between 30 and 70% of the population were aware of their HIV status. In 2009, between 3.6 and 42% of men and women in Sub-Saharan countries were tested which represented a significant increase compared to previous years.
Specific age groups, persons who participate in risky sexual behavior, or those have certain health conditions may require screening. The CDC recommends that sexually active women under the age of 25 and those over 25 at risk should be screened for chlamydia and gonorrhea yearly. Appropriate times for screening are during regular pelvic examinations and preconception evaluations. Nucleic acid amplification tests are the recommended method of diagnosis for gonorrhea and chlamydia. This can be done on either urine in both men and women, vaginal or cervical swabs in women, or urethral swabs in men. Screening can be performed:
- to assess the presence of infection and prevent tubal infertility in women
- during the initial evaluation before infertility treatment
- to identify HIV infection
- for men who have sex with men
- for those who may have been exposed to hepatitis C
- for HCV
HIV/AIDS is diagnosed via laboratory testing and then staged based on the presence of certain signs or symptoms. HIV screening is recommended by the United States Preventive Services Task Force for all people 15 years to 65 years of age including all pregnant women. Additionally, testing is recommended for those at high risk, which includes anyone diagnosed with a sexually transmitted illness. In many areas of the world, a third of HIV carriers only discover they are infected at an advanced stage of the disease when AIDS or severe immunodeficiency has become apparent.
According to current recommendations by the WHO, US CDC and U.S. Department of Health and Human Services (DHHS), all individuals with HIV should begin ART. The recommendation is stronger under the following conditions:
- CD4 count below 350 cells/mm
- High viral load (>100,000 copies/ml)
- Progression of HIV to AIDS
- Development of HIV-related infections and illnesses
- Pregnancy
Women are encouraged to begin treatment as soon as they are diagnosed with HIV. If they are diagnosed prior to pregnancy, they should continue with ART during the pregnancy. If the diagnosis of HIV is made during the pregnancy, ART should be initiated immediately.
Testing may be for a single infection, or consist of a number of tests for a range of STIs, including tests for syphilis, trichomonas, gonorrhea, chlamydia, herpes, hepatitis and HIV. No procedure tests for all infectious agents.
STI tests may be used for a number of reasons:
- as a diagnostic test to determine the cause of symptoms or illness
- as a screening test to detect asymptomatic or presymptomatic infections
- as a check that prospective sexual partners are free of disease before they engage in sex without safer sex precautions (for example, when starting a long term mutually monogamous sexual relationship, in fluid bonding, or for procreation).
- as a check prior to or during pregnancy, to prevent harm to the baby
- as a check after birth, to check that the baby has not caught an STI from the mother
- to prevent the use of infected donated blood or organs
- as part of the process of contact tracing from a known infected individual
- as part of mass epidemiological surveillance
Early identification and treatment results in less chance to spread disease, and for some conditions may improve the outcomes of treatment. There is often a window period after initial infection during which an STI test will be negative. During this period, the infection may be transmissible. The duration of this period varies depending on the infection and the test. Diagnosis may also be delayed by reluctance of the infected person to seek a medical professional. One report indicated that people turn to the Internet rather than to a medical professional for information on STIs to a higher degree than for other sexual problems.
A study conducted on 452 patients revealed that the genotype responsible for higher IL-10 expression makes HIV infected people more susceptible to tuberculosis infection. Another study on HIV-TB co-infected patients also concluded that higher level of IL-10 and IL-22 makes TB patient more susceptible to Immune reconstitution inflammatory syndrome (IRIS). It is also seen that HIV co-infection with tuberculosis also reduces concentration of immunopathogenic matrix metalloproteinase (MMPs) leading to reduced inflammatory immunopathology.
The virus that causes AIDS is the best known of the transfusion-transmitted infections because of high-profile cases such as Ryan White, a haemophiliac who was infected through factor VIII, a blood-derived medicine used to treat the disease. Another person who died of medically acquired HIV/AIDS was Damon Courtenay, who died in 1991 due to a bad batch of factor VIII.
The standard test for HIV is an enzyme immunoassay test that reacts with antibodies to the virus. This test has a window period where a person will be infected but not yet have an immune response. Other tests are used to look for donors during this period, specifically the p24 antigen test and nucleic acid testing.
In addition to the general risk criteria for viruses, blood donors are sometimes excluded if they have lived in certain parts of Africa where subtypes of HIV that are not reliably detected on some tests are found, specifically HIV group O. People who have been in prison for extended periods are also excluded for HIV risk.
Prevalence measures include everyone living with HIV and AIDS, and present a delayed representation of the epidemic by aggregating the HIV infections of many years. Incidence, in contrast, measures the number of new infections, usually over the previous year. There is no practical, reliable way to assess incidence in Sub-Saharan Africa. Prevalence in 15- to 24-year-old pregnant women attending antenatal clinics is sometimes used as an approximation. The test done to measure prevalence is a serosurvey in which blood is tested for the presence of HIV.
Health units that conduct serosurveys rarely operate in remote rural communities, and the data collected also does not measure people who seek alternate healthcare. Extrapolating national data from antenatal surveys relies on assumptions which may not hold across all regions and at different stages in an epidemic.
Recent national population or household-based surveys collecting data from both sexes, pregnant and non-pregnant women, and rural and urban areas, have adjusted the recorded national prevalence levels for several countries in Africa and elsewhere. These, too, are not perfect: people may not participate in household surveys because they fear they may be HIV positive and do not want to know their test results. Household surveys also exclude migrant labourers, who are a high risk group.
Thus, there may be significant disparities between official figures and actual HIV prevalence in some countries.
A minority of scientists claim that as many as 40 percent of HIV infections in African adults may be caused by unsafe medical practices rather than by sexual activity. The World Health Organization states that about 2.5 percent of HIV infections in Sub-Saharan Africa are caused by unsafe medical injection practices and the "overwhelming majority" by unprotected sex.
When HIV-negative children take isoniazid after they have been exposed to tuberculosis, their risk to contract tuberculosis is reduced. A Cochrane review investigated whether giving isoniazid to HIV-positive children can help to prevent this vulnerable group from getting tuberculosis. They included three trials conducted in South Africa and Botswana and found that isoniazid given to all children diagnosed with HIV may reduce the risk of active tuberculosis and death in children who are not on antiretroviral treatment. For children taking antiretroviral medication, no clear benefit was detected.
Many of these viruses are controlled through laboratory screening tests. These fall into three basic varieties: antibody tests, nucleic acid tests (NAT), and surrogate tests. Antibody tests look for the immune system's response to the infection. Nucleic acid tests look for the genetic material of the virus itself. The third variety are tests that are not specific to the disease but look for other related conditions.
High risk activities for transfusion transmitted infections vary, and the amount of caution used for screening donors varies based on how dangerous the disease is. Most of the viral diseases are spread by either sexual contact or by contact with blood, usually either drug use, accidental needle injuries among health care workers, unsterilized tattoo and body piercing equipment, or through a blood transfusion or transplant. Other vectors exist.
Whether a donor is considered to be at "too high" of a risk for a disease to be allowed to donate is sometimes controversial, especially for sexual contact. High risk sexual activity is defined in many different ways, but usually includes:
- Sex in exchange for money or drugs.
- Men who have sex with men, the most controversial criterion.
- A recent history of sexually transmitted disease.
- Sex with a person who has had a positive test or was at high risk for a disease that can be spread in blood transfusions.
When physical examination of the newborn shows signs of a vertically transmitted infection, the examiner may test blood, urine, and spinal fluid for evidence of the infections listed above. Diagnosis can be confirmed by culture of one of the specific pathogens or by increased levels of IgM against the pathogen.
Many people living with HIV in low and middle income countries who need antiretroviral therapy are unable to access or remain in care. This is often because of the time and cost required to travel to health centres as well as an inadequate number of trained staff such as medical doctors and specialists to provide treatment. One approach to improve access to HIV care is to provide antiretroviral therapy close to people’s homes. A systematic review found that when antiretroviral treatment was initiated at the hospital but followed up at a health centre closer to home, fewer patients died or were lost to follow up. The research also did not detect a difference in the numbers of patients who died or were lost to follow up when they received maintenance treatment in the community rather than in a health centre or hospital.
Cryptococcosis is a very subacute infection with a prolonged subclinical phase lasting weeks to months in persons with HIV/AIDS before the onset of symptomatic meningitis. In Sub-Saharan Africa, the prevalence rates of detectable cryptococcal antigen in peripheral blood is often 4–12% in persons with CD4 counts lower than 100 cells/mcL.
Cryptococcal antigen screen and preemptive treatment with fluconazole is cost saving to the healthcare system by avoiding cryptococcal meningitis. The World Health Organization recommends cryptococcal antigen screening in HIV-infected persons entering care with CD4<100 cells/μL. This undetected subclinical cryptococcal (if not preemptively treated with anti-fungal therapy) will often go on to develop cryptococcal meningitis, despite receiving HIV therapy. Cryptococcosis accounts for 20-25% of the mortality after initiating HIV therapy in Africa. What is effective preemptive treatment is unknown, with the current recommendations on dose and duration based on expert opinion. Screening in the United States is controversial, with official guidelines not recommending screening, despite cost-effectiveness and a 3% U.S. cryptococcal antigen prevalence in CD4<100 cells/μL.
Dependent on the infectious syndrome, symptoms include fever, fatigue, dry cough, headache, blurred vision, and confusion. Symptom onset is often subacute, progressively worsened over several weeks. The two most common presentations are meningitis (an infection in and around the brain) and pulmonary (lung) infection.
Detection of cryptococcal antigen (capsular material) by culture of CSF, sputum and urine provides definitive diagnosis. Blood cultures may be positive in heavy infections. India ink of the CSF is a traditional microscopic method of diagnosis, although the sensitivity is poor in early infection, and may miss 15-20% of patients with culture-positive cryptococcal meningitis. Unusual morphological forms are rarely seen. Cryptococcal antigen from cerebrospinal fluid is the best test for diagnosis of cryptococcal meningitis in terms of sensitivity. Apart from conventional methods of detection like direct microscopy and culture, rapid diagnostic methods to detect cryptococcal antigen by latex agglutination test, lateral flow immunochromatographic assay (LFA), or enzyme immunoassay (EIA). A new cryptococcal antigen LFA was FDA approved in July 2011. Polymerase chain reaction (PCR) has been used on tissue specimens.
Cryptococcosis can rarely occur in the non-immunosuppressed people, particularly with "Cryptococcus gattii".
Some vertically transmitted infections, such as toxoplasmosis and syphilis, can be effectively treated with antibiotics if the mother is diagnosed early in her pregnancy. Many viral vertically transmitted infections have no effective treatment, but some, notably rubella and varicella-zoster, can be prevented by vaccinating the mother prior to pregnancy.
If the mother has active herpes simplex (as may be suggested by a pap test), delivery by Caesarean section can prevent the newborn from contact, and consequent infection, with this virus.
IgG antibody may play crucial role in prevention of intrauterine infections and extensive research is going on for developing IgG-based therapies for treatment and vaccination.
HIV superinfection (also called HIV reinfection) is a condition in which a person with an established human immunodeficiency virus infection acquires a second strain of HIV, often of a different subtype. The HIV superinfection strain (a recombinant strain) appears when a person becomes simultaneously infected by two different strains, allowing the two viruses to exchange genetic material, resulting in a new unique strain that can possess the resistances of both previous strains. This new strain co-exists with the two prior strains and may cause more rapid disease progression or carry multiple resistances to certain HIV medications.
People with HIV risk superinfection by the same actions that would place a non-infected person at risk of acquiring HIV. These include sharing needles and forgoing condoms with HIV-positive sexual partners. For many years superinfection was thought to occur mainly in high-risk populations. Research from Uganda published in 2012 indicates that HIV superinfection among HIV-infected individuals within a general population remains unknown. Further research from "The Journal of Infectious Diseases" indicates that there have been 16 documented cases of superinfection since 2002.
It is unknown what aspects of the natural immune response to HIV may protect someone from superinfection, but it has been shown that cytotoxic lymphocyte responses do not seem to be protective. In addition, it has been demonstrated that superinfection can occur in individuals that demonstrate a robust anti-HIV antibody response. The anti-HIV antibody response broadens and strengthens in individuals post-superinfection.
Taken with the finding that super-infection is common and occurs within and between HIV subtypes it has been suggested that the immune response elicited by primary infection may confer limited protection and raises concerns that HIV-vaccine strategies designed to replicate the natural anti-HIV immune response may have limited effectiveness in preventing new infections. However at the same time, HIV-infected individuals at high risk for super-infection who do not become superinfected may also provide a very interesting avenue for new vaccine research.
Use of male condoms or female condoms may help prevent the spread of trichomoniasis, although careful studies have never been done that focus on how to prevent this infection. Infection with Trichomoniasis through water is unlikely because "Trichomonas vaginalis" dies in water after 45–60 minutes, in thermal water after 30 minutes to 3 hours and in d urine after 5–6 hours.
Currently there are no routine standard screening requirements for the general U.S. population receiving family planning or STI testing. The Centers for Disease Control and Prevention (CDC) recommends Trichomoniasis testing for females with vaginal discharge and can be considered for females at higher risk for infection or of HIV-positive serostatus.
The advent of new, highly specific and sensitive trichomoniasis tests present opportunities for new screening protocols for both men and women. Careful planning, discussion, and research are required to determine the cost-efficiency and most beneficial use of these new tests for the diagnosis and treatment of trichomoniasis in the U.S., which can lead to better prevention efforts.
A number of strategies have been found to improve follow-up for STI testing including email and text messaging as reminders of appointments.
There are three main ways to test for Trichomoniasis.
- The first is known as saline microscopy. This is the most commonly used method and requires an endocervical, vaginal, or penile swab specimen for examination under a microscope. The presence of one or multiple trichomonads constitutes a positive result. This method is cheap but has a low sensitivity (60-70%) often due to an inadequate sample, resulting in false negatives.
- The second diagnostic method is culture, which has historically been the "gold standard" in infectious disease diagnosis. Trichomonas Vaginalis culture tests are relatively cheap; however, sensitivity is still somewhat low (70-89%).
- The third method includes the nucleic acid amplification tests (NAATs) which are more sensitive. These tests are more costly than microscopy and culture, and are highly sensitive (80-90%).
Successful diagnosis of XDR-TB depends on the patient’s access to quality health-care services. If TB bacteria are found in the sputum, the diagnosis of TB can be made in a day or two, but this finding will not be able to distinguish between drug-susceptible and drug-resistant TB. To evaluate drug susceptibility, the bacteria need to be cultivated and tested in a suitable laboratory. Final diagnosis in this way for TB, and especially for XDR-TB, may take from 6 to 16 weeks. To reduce the time needed for diagnosis, new tools for rapid TB diagnosis are urgently needed.
The original method used to test for MDR-TB and XDR-TB was the Drug Susceptibility Testing (DST). DST is capable of determining how well four primary antitubercular drugs inhibit the growth of Mycobacterium Tuberculosis. The four primary antitubercular drugs are Isoniazid, Rifampin, Ethambutol and Pyrazinamide. Drug Susceptibility testing is done by making a Lowenstein-Jensen medium plate and spreading the bacteria on the plate. Disks containing one of the four primary drugs are added to the plate. After weeks of allowing the bacteria to grow the plate is checked for clear areas around the disk. If there is a clear area, the drug has killed the bacteria and most likely the bacteria is not resistant to that drug.
As "Mycobacterium tuberculosis" evolved new strains of resistant bacteria were being found such as XDR-TB. The problem was that primary DST was not suitable for testing bacteria strains that were extensively drug resistant. This problem was starting to be fixed when drug susceptibility tests started including not just the four primary drugs, but secondary drugs. This secondary test is known as Bactec MGIT 960 System. Although Bactec MGIT 960 System was accurate it was still slow at determining the level of resistance.
Diagnosis of MDR and XDR-TB in children is challenging. With an increasing number of cases being reported worldwide there is a great need for better diagnostic tools available for pediatric patients.
In recent years drug resistant tuberculosis testing has shown a lot of progress. Some studies have found an in-house assay that could rapidly detect resistance to drugs involved in the definition of XDR-TB directly from smear-positive specimens. The assay is called Reverse Line Blot Hybridization Assay also known as RLBH. The study showed that the results of RLBH were as accurate as other drug susceptibility tests, but at the same time didn`t take weeks to get results. RLBH testing only took 3 days to determine how resistant the strain of bacteria was.
The current research has shown progress in the testing of drug resistance. A recent study found that a research technique known as direct nitrate reductase assay (D-NRA) showed efficient accuracy for the rapid and simultaneous detection of resistance to isoniazid (INH), rifampicin (RIF), kanamycin (KAN) and ofloxacin (OFL). D-NRA results were obtained in 16.9 days, comparably less than other drug susceptibility testing. At the same time the study mentioned how D-NRA is a low-cost technology, easy to set up in clinical laboratories and suitable to be used for DST of M. tuberculosis in all smear-positive samples.
Exposure to antiretroviral treatments has led to the evolution of HIV in response to selection pressure that eliminates strains of HIV that do not express resistance mechanisms. Drug resistance occurs in all antiretroviral treatments if patients are non-adherent, meaning that they do not take their medication regimens as prescribed. Lack of adherence may result from unreliable access to the medication, due to prohibitive cost or inadequate supply.
Current medical and scientific opinion is mixed on the most effective treatment methods, but is focused on drug cocktails and the importance of first-line regimens . The World Health Organization advocates a public-health approach to HIV treatment in order to make treatment uniform and available to patients around the world. As of July 2017, the WHO is implementing the Global Action Plan on HIV drug resistance 2017-2021. It is a 5-year initiative intended to help countries around the world manage HIV drug resistance.
Among treatment methods, the World Health Organization acknowledges the importance of successful first-line treatments. First-line treatments are known to affect the virus’ future response to other treatments, making the effectiveness of first-line treatments an issue of vital importance. The most successful treatments are combinations of three drugs used simultaneously, as this greatly reduces the probability of the virus developing resistance.
In an effort to further refine the United Nations guideline for optimal infant feeding options for HIV-infected mothers, the World Health Organization (WHO) held a three-day convention in Geneva in 2006 to review new evidence that had been established since they last established a guideline in 2000. Participants included UN agencies, representative from nongovernmental organizations, researchers, infant feeding experts, and WHO headquarters departments. The convention concluded with the following recommendations: If replacement feeding is acceptable, feasible, affordable and safe, HIV-infected mothers are recommended to use replacement feeding. Otherwise, exclusive breastfeeding is recommended. At six months, if replacement feeding is still not available, HIV-infected mothers are encouraged to slowly introduce food while continuing breastfeeding. Those with HIV-infected infants are recommended to continue breastfeeding even after 6 months.
In microbiology, coinfection is the simultaneous infection of a host by multiple pathogen species. In virology, coinfection includes simultaneous infection of a single cell by two or more virus particles. An example is the coinfection of liver cells with Hepatitis B virus and Hepatitis D virus, which can arise incrementally by initial infection followed by superinfection.
Global prevalence or incidence of coinfection among humans is unknown, but it is thought to be commonplace, sometimes more common than single infection. Coinfection with helminths affects around 800 million people worldwide.
Coinfection is of particular human health importance because pathogen species can interact within the host. The net effect of coinfection on human health is thought to be negative. Interactions can have either positive or negative effects on other parasites. Under positive parasite interactions, disease transmission and progression are enhanced and this is also known as syndemism. Negative parasite interactions include microbial interference when one bacterial species suppresses the virulence or colonisation of other bacteria, such as "Pseudomonas aeruginosa" suppressing pathogenic "Staphylococcus aureus" colony formation. The general patterns of ecological interactions between parasite species are unknown, even among common coinfections such as those between sexually transmitted infections. However, network analysis of a food web of coinfection in humans suggests that there is greater potential for interactions via shared food sources than via the immune system.
A globally common coinfection involves tuberculosis and HIV. In some countries, up to 80% of tuberculosis patients are also HIV-positive. The potential for dynamics of these two infectious diseases to be linked has been known for decades. Other common examples of coinfections are AIDS, which involves coinfection of end-stage HIV with opportunistic parasites and polymicrobial infections like Lyme disease with other diseases.
Long-term nonprogressors (LTNPs), sometimes also called "elite controllers", are individuals infected with HIV, who maintain a CD4 count greater than 500 without antiretroviral therapy with a detectable viral load. Many of these patients have been HIV positive for 30 years without progressing to the point of needing to take medication in order not to develop AIDS. They have been the subject of a great deal of research, since an understanding of their ability to control HIV infection may lead to the development of immune therapies or a therapeutic vaccine. The classification "Long-term non-progressor" is not permanent, because some patients in this category have gone on to develop AIDS.
Long-term nonprogressors typically have viral loads under 10,000 copies RNA/ml blood, do not take antiretrovirals, and have CD4+ counts within the normal range. Most people with HIV not on medication have viral loads which are much higher.
It is estimated that around 1 in 300 people with HIV are long-term nonprogressors. Without the symptoms of AIDS, many LTNP patients may not know they are infected.
Genetic traits that confer greater resistance or more robust immune response to HIV are thought to explain why LTNP patients are able to live much longer with HIV than patients who are not LTNP. Some LTNP are infected with a weakened or inactive form of HIV, but it is now known that many LTNP patients carry a fully virulent form of the virus. Genetic traits that may affect progression include:
- Gene mutation. A mutation in the FUT2 gene affects the progression of HIV-1 infection. 20% of Europeans who have that mutation are called "non secretor" because of their absence of a certain type of antigen that also provides strong resistance against norovirus.
- Mitochondrial DNA. Different mitochondrial DNA haplotypes in humans may increase or decrease rates of AIDS progression. Haplotypes associated with more loosely coupled mitochondrial respiration, with reduced ATP and ROS generation, have been associated with faster progression and vice versa.
- Receptor mutations. A low percentage of long-term nonprogressors have been shown to have inherited mutations of the CCR5 receptor of T cell lymphocytes. HIV uses CCR5 to enter these cells. It is believed that the Δ32 (delta 32) variant of CCR5 impairs HIV ability to infect cells and cause disease. An understanding of this mechanism led to the development of a class of HIV medicines, the entry inhibitors. The presence of this mutation, however, is not a unifying theme among LTNPs and is observed in an exceedingly small number of these patients.
- HLA type has also been correlated with long-term non-progressor cohorts. In particular, strong correlations have been found between possessing the class 1 HLA-B*5701, HLA-B*5703, and/or HLA-B*2705 alleles and ability to exert control over HIV.
- Antibody production. All individuals with HIV make antibodies against the virus. In most patients, broadly neutralizing antibodies do not emerge until approximately 2–4 years after the initial infection. At this point, the latent reservoir has already been established and the presence of broadly neutralizing antibodies is not enough to prevent disease progression. In some rare patients, these antibodies emerge earlier and can result in a delayed disease course. These patients, however, are not typically classified as LTNPs, but rather as slow progressors, who will eventually develop AIDS. Induction of broadly neutralizing antibodies in healthy individuals is a potential strategy for a preventive HIV vaccine, as is the elicitation of these antibodies through rationally designed immunogens. Direct production of these antibodies in somatic tissue through plasmid transfection also pose a viable method for making these antibodies available in a large number of humans.
- APOBEC3G protein production. In a small number of people infected with HIV, the virus is naturally suppressed without medical treatment. These people may carry high quantities of a protein called APOBEC3G that disrupts viral replication in cells. APOBEC3G, or "A3" for short, is a protein that sabotages reverse transcription, the process HIV relies on for its replication. This process involves the virus transcribing its singe-stranded RNA genome into double-stranded DNA that is incorporated into the cell's genome. A3 usually stops dormant viruses in the human genome, called endogenous retroviruses, from reawakening and causing infections.