Factors affecting HIV progression

Related Terms

Acquired immune deficiency syndrome, acquired immunodeficiency syndrome, AIDS, alcohol, antiretroviral, antiretroviral therapy, ART, blood test, Candida albicans,CD4 cells, CD4 T-cells, CD8 T-cells, chemical messengers, chemokines, cocaine, cytokines, cytomegalovirus, drug use, emphysema, genetics, HAART, HCV, hepatitis C virus, hereditary, herpes, highly active antiretroviral therapy, HIV, HLA, human immunodeficiency virus, human leukocyte antigens, immune, immune defense system, immune system, immune response, immunocompromised, immunodeficiency, inhaled nitrates, injection-drug use, infection, leukocytes, lung infection, lymphocytes, lymphoid organs, multi-drug transporters, multidrug, OI, opportunistic infection, marijuana, methamphetamine, nutrition, poppers, retrovirus, stress, superinfection, thrush, viral, viral infection, viral load, viral set-point, virus, vitamin A, vitamin B12, weakened immune system, white blood cells, zinc.

Background

The human immunodeficiency virus (HIV) is a retrovirus that causes AIDS (acquired immune deficiency syndrome). The retrovirus primarily attacks the immune defense system, making the body extremely vulnerable to opportunistic infections. Opportunistic infections occur in individuals who are immunocompromised (have weakened immune systems).
HIV is transmitted from person to person via bodily fluids, including blood, semen, vaginal discharge, and breast milk. It can be spread by sexual contact with an infected person, by sharing needles/syringes with someone who is infected, through breastfeeding, during vaginal birth or, less commonly (and rare in countries where blood is screened for HIV antibodies), through transfusions with infected blood. HIV has been found in saliva and tears in very low quantities and concentrations in some AIDS patients. However, contact with saliva, tears, or sweat has never been shown to result in HIV transmission.
Currently, there is no cure for HIV/AIDS. Patients receive antiretroviral drugs, which suppress the virus. These drugs do not reduce the risk of transmitting the disease to someone else.
HIV can infect and kill many different types of cells in the body, but the primary targets are immune cells called CD4 T-cells. The CD4 T-cells are white blood cells that help coordinate the immune system's response to infection and disease. These cells express a molecule called CD4 on their surfaces, which allows them to detect foreign substances, including viruses that enter the body. HIV binds to the receptors on CD4 cells and enters the white blood cell. Once inside the cell, HIV begins replicating.
The first stage of HIV, known as the primary or acute infection, is the most infectious stage of the disease, and it typically lasts several weeks. During this phase, the virus replicates rapidly, which leads to an abundance of the virus in the bloodstream, and a drastic decline in the number of CD4 T-cells. The CD8 T-cells (cells that kill abnormal or infected body cells) are then activated to destroy HIV-infected body cells and antibodies are produced. An estimated 80-90% of HIV patients experience flu-like symptoms during this stage.
The next stage, called clinical latency, may last anywhere from two weeks to 20 years. During this phase, HIV is active in the lymph nodes, where large amounts of the virus become trapped. The surrounding tissues, which contain high levels of CD4 T-cells, may also become infected. The virus accumulates in infected cells and in the blood as free virus.
Patients progress to AIDS when their CD4 cell counts drop below 200 cells per microliter of blood. Healthy individuals have a CD4 cell count between 600 and 1,200 cells per microliter of blood. Individuals with a CD4 cell lower than 200 cells per microliter of blood have the greatest risk of developing opportunistic infections.
Many factors can affect how quickly HIV infection progresses to AIDS. Factors such as age, co-infections (infection other than HIV), ethnicity, geographic location, genetics, infection route (how the disease was transmitted), nutrition, pregnancy, stress, and whether or not the patient smokes or uses recreational drugs can affect the rate at which an HIV patient develops AIDS. In addition, the healthcare provider's experience treating HIV can influence how quickly the virus progresses.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

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Liu KL, Peters V, Weedon J, et al. l. Sex differences in morbidity and mortality among children with perinatally acquired human immunodeficiency virus infection in New York City. Arch Pediatr Adolesc Med. 2004 Dec;158(12):1187-8.
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Integrative therapies

Note: Integrative therapies should not be used in place of antiretroviral therapy. Patients should consult their healthcare providers before taking any herbs or supplements because they may interact with treatment.
Unclear or conflicting scientific evidence:
Aloe vera: Clear gel from the pulp of Aloe vera leaves has been used on the skin for thousands of years to treat wounds, skin infections, minor burns and other skin conditions. Although aloe has been suggested as a possible treatment for HIV, further research is needed before a firm conclusion can be made.
Avoid if allergic to aloe or other plants of the Liliaceae family (garlic, onions, tulips). Avoid injecting aloe. Do not apply to open skin, surgical wounds or pressure ulcers. Avoid taking by mouth with diarrhea, bowel blockage, intestinal diseases, bloody stools or hepatitis. Avoid with a history of irregular heartbeat (arrhythmia), electrolyte imbalances, diabetes, heart disease or kidney disease. Avoid taking by mouth if pregnant or breastfeeding.
Antineoplastons: Antineoplastons are substances found in human blood and urine. A small preliminary study reported increased energy and weight in patients with HIV, as well as a decreased number of opportunistic infections, and increased CD4 cell counts. These patients were treated with antineoplaston AS2-1. However, this evidence cannot be considered conclusive. Currently, there are drug therapy regimens available for HIV with clearly demonstrated effects (highly active anti-retroviral therapy), and patients with HIV are recommended to consult with their physicians about treatment options.
Avoid if allergic or hypersensitive to antineoplastons. Use cautiously with high medical or psychiatric risk. Use cautiously with an active infection due to a possible decrease in white blood cells. Use cautiously with high blood pressure, heart conditions, chronic obstructive pulmonary disease, liver disease/damage or kidney disease/damage. Avoid if pregnant or breastfeeding.
Beta sitosterol: Beta-sitosterol is found in plant-based foods, such as fruits, vegetables, soybeans, breads, peanuts and peanut products. It is also found in bourbon and oils (such as olive oil, flaxseed and tuna). Due to data that suggest immune modulating effects of beta-sitosterol and beta-sitosterol glucoside, these sterols have been studied in combination in the treatment of HIV. Larger populations of patients with HIV should be evaluated in randomized controlled trials to draw any conclusions.
Avoid if allergic or hypersensitive to beta-sitosterol, beta-sitosterol glucoside or pine. Use cautiously with asthma or breathing disorders, diabetes, primary biliary cirrhosis (destruction of the small bile duct in the liver), ileostomy, neurodegenerative disorders (like Parkinson's disease or Alzheimer's disease), diverticular disease (bulging of the colon), short bowel syndrome, celiac disease and sitosterolemia. Use cautiously with a history of gallstones. Avoid if pregnant or breastfeeding.
Bitter melon: Laboratory studies have shown that a protein in bitter melon called MAP30 may have antiviral activity. However, this has not been studied in humans. Further research is needed before a firm conclusion can be made.
Avoid if allergic to bitter melon or members of the Curcurbitaceae (gourd or melon) family. Avoid ingesting bitter melon seeds. Avoid with glucose-6-phosphate dehydrogenase deficiency. Use cautiously with diabetes, glucose intolerance or with hypoglycemic agents due to the risk of hypoglycemia. Avoid if pregnant or breastfeeding.
Chiropractic: Chiropractic care focuses on how the relationship between musculoskeletal structure (mainly the spine) and bodily function (mainly nervous system) affects health. There is not enough reliable scientific evidence to conclude the effects of chiropractic techniques on CD4 cell count or quality of life in patients with HIV/AIDS.
Use extra caution during cervical adjustments. Use cautiously with acute arthritis, conditions that cause decreased bone mineralization, brittle bone disease, bone softening conditions, bleeding disorders or migraines. Use cautiously with the risk of tumors or cancers. Avoid with symptoms of vertebrobasilar vascular insufficiency, aneurysms, unstable spondylolisthesis or arthritis. Avoid with agents that increase the risk of bleeding. Avoid in areas of para-spinal tissue after surgery. Avoid if pregnant or breastfeeding due to a lack of scientific data.
Coenzyme Q10: Coenzyme Q10 (CoQ10) is produced by the body, and it is necessary for basic functioning of cells. CoQ10 levels decrease with age. There is limited evidence that natural levels of CoQ10 in the body may be reduced in people with HIV/AIDS. There is no reliable scientific research showing that CoQ10 supplements have any effect on this disease.
There are currently no documented cases of allergy associated with Coenzyme Q10 supplements, although rash and itching have rarely been reported. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk and do not use immediately after these procedures. Use cautiously with history of blood clots, diabetes, high blood pressure, heart attack or stroke. Use cautiously with anticoagulants (blood thinners), antiplatelet drugs, blood pressure drugs, blood sugar drugs, cholesterol drugs or thyroid drugs. Avoid if pregnant or breastfeeding.
DHEA: DHEA (Dehydroepiandrosterone) is a hormone that is secreted by the adrenal glands. Although some studies suggest that DHEA supplementation may be beneficial in patents with HIV, results from different studies do not agree with each other. There is currently not enough scientific evidence to recommend DHEA for this condition, and other therapies are more proven in this area.
Avoid if allergic to DHEA. Avoid with a history of seizures. Use cautiously with adrenal or thyroid disorders. Use cautiously if taking anticoagulants, or drugs, herbs or supplements for diabetes, heart disease, seizures or stroke. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Avoid if pregnant or breastfeeding.
Flaxseed: Flaxseed and flaxseed oil/linseed oil are rich sources of the essential fatty acid alpha-linolenic acid (omega-6). While flaxseed has been used to treat HIV, no strong evidence supports its use, and no recommendation can be made without further research.
Flaxseed has been well tolerated in studies for up to four months. Avoid if allergic to flaxseed, flaxseed oil or other plants of the Linaceae family. Avoid with prostrate cancer, breast cancer, uterine cancer or endometriosis. Avoid ingestion of immature flaxseed pods. Avoid large amounts of flaxseed by mouth and mix plenty of water or liquid. Avoid flaxseed (not flaxseed oil) with history of esophageal stricture, ileus, gastrointestinal stricture or bowel obstruction. Avoid with history of acute or chronic diarrhea, irritable bowel syndrome (IBS), diverticulitis or inflammatory bowel disease (IBD). Avoid topical flaxseed in open wounds or abraded skin surfaces. Use cautiously with history of a bleeding disorder or with drugs that increase the risk of bleeding (such as anticoagulants and non-steroidal anti-inflammatories). Use cautiously with high triglyceride levels, diabetes, mania, seizures or asthma. Avoid if pregnant or breastfeeding.
Healing Touch: Healing touch (HT) is a combination of hands-on and off-body techniques to influence the flow of energy through a person's biofield. Data from small preliminary studies are insufficient to support any recommendations for or against use of HT in HIV/AIDS. Studies of better design are needed before any conclusions can be reached.
HT should not be regarded as a substitute for established medical treatments. Use cautiously if pregnant or breastfeeding.
L-carnitine: L-carnitine may be beneficial in AIDS treatment by increasing proliferation of mononuclear cells and increasing CD4 counts. Additional study is needed to make a firm recommendation
Avoid if allergic or hypersensitive to carnitine. Use cautiously with peripheral vascular disease, high blood pressure, alcohol-induced liver cirrhosis and diabetes. Use cautiously in low birth weight infants and individuals on hemodialysis. Use cautiously if taking anticoagulants (blood thinners), beta-blockers or calcium channel blockers. Avoid if pregnant or breastfeeding.
Meditation: Various forms of meditation have been practiced for thousands of years throughout the world, with many techniques originating in Eastern religious practices. A common goal is to attain a state of "thoughtless awareness" of sensations and mental activities occurring at the present moment. More studies are needed to establish how meditation may be useful as an adjunctive therapy in HIV/AIDS patients.
Use cautiously with underlying mental illnesses. People with psychiatric disorders should consult with their primary mental healthcare professionals before starting a program of meditation, and they should explore how meditation may or may not fit in with their current treatment plans. Avoid with risk of seizures. The practice of meditation should not delay the time to diagnosis or treatment with more proven techniques or therapies, and it should not be used as the sole approach to illnesses.
Melatonin: Melatonin is a neurohormone produced in the brain. There is a lack of well-designed scientific evidence to recommend for or against the use of melatonin as a treatment for AIDS. Melatonin should not be used in place of more proven therapies, and patients with HIV/AIDS should be treated under the supervision of their healthcare professionals.
Based on available studies and clinical use, melatonin is generally regarded as safe in recommended doses for short-term use. There are rare reports of allergic skin reactions after taking melatonin by mouth. Use cautiously with bleeding disorders, seizure disorders or if taking drugs that increase the risk of bleeding.
Mistletoe: Once considered a sacred herb in Celtic tradition, mistletoe has been used for centuries for high blood pressure, epilepsy, exhaustion, anxiety, arthritis, vertigo (dizziness) and degenerative inflammation of the joints. Treatment of HIV patients with mistletoe has been done in Europe since the beginning of the AIDS epidemic. Treatment seems to be tolerable with minimal side effects reported. Mistletoe may assist in inhibiting disease progression. However, not all mistletoe preparations have shown equal effects. Further study is needed before a firm conclusion can be made.
Avoid if allergic or hypersensitive to mistletoe or to any of its constituents. Anaphylactic reactions (life threatening, shock) have been described after injections of mistletoe. Avoid with acute, highly febrile, inflammatory disease, thyroid disorders, seizure disorders or heart disease. Use cautiously with diabetes, glaucoma or with cholinergics.
Prayer/distant healing: Prayer can be defined as a "reverent petition," the act of asking for something while aiming to connect with God or another object of worship. Limited study of prayer in patients with AIDS reports fewer new AIDS-related illnesses and hospitalizations. However, due to methodological problems, these results cannot be considered conclusive.
Prayer is not recommended as the sole treatment approach for potentially serious medical conditions, and it should not delay the time it takes to consult with a healthcare professional or receive established therapies. Sometimes religious beliefs come into conflict with standard medical approaches and require an open dialog between patients and caregivers.
Psychotherapy: Psychotherapy is an interactive process between a person and a qualified mental health professional. The patient will explore thoughts, feelings and behavior to help with problem solving. Psychotherapy, especially supportive psychotherapy, may reduce depression in HIV-positive patients. It may also help with treating substance abuse when used in combination with prescription medicine. Supportive-expressive group therapy may also have concomitant improvements in CD4 cell count and viral load. More research is needed in this area, especially to determine the best type of psychotherapy.
Psychotherapy cannot always fix mental or emotional conditions. Psychiatric drugs are sometimes needed. In some cases symptoms may get worse if the proper medication is not taken. Not all therapists are qualified to work with all problems. Use cautiously with serious mental illness or some medical conditions because some forms of psychotherapy may stir up strong emotional feelings and expression.
Relaxation therapy: Relaxation techniques include behavioral therapeutic approaches that differ widely in philosophy, methodology and practice. Mental health and quality-of-life improvements have been seen in preliminary studies of HIV/AIDS patients. These findings suggest the need for further, well-controlled research.
Avoid with psychiatric disorders like schizophrenia/psychosis. Jacobson relaxation (flexing specific muscles, holding that position, then relaxing the muscles) should be used cautiously with illnesses like heart disease, high blood pressure or musculoskeletal injury. Relaxation therapy is not recommended as the sole treatment approach for potentially serious medical conditions, and it should not delay the time to diagnosis or treatment with more proven techniques.
Selenium: Selenium is a mineral found in soil, water and some foods. Selenium supplementation has been studied in HIV/AIDS patients, and some reports associate low selenium levels with complications, such as cardiomyopathy. It remains unclear if selenium supplementation is beneficial in patients with HIV, particularly during antiretroviral therapy.
Avoid if allergic or sensitive to products containing selenium. Avoid with history of non-melanoma skin cancer. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects.
Shiitake: Shiitake mushrooms were originally grown on natural oak logs found in Japan. Today, they are available in the United States. These mushrooms are large, black-brown and have an earthy rich flavor. Based on preliminary studies, lentinan may increase CD4 counts and may qualify in future multi-drug studies in HIV patients. Further well-designed studies are needed to confirm these results. Side effects have been reported and more proven therapies are recommended at this time.
Avoid if allergic or hypersensitive to shiitake mushrooms. Avoid if pregnant or breastfeeding.
Thymus extract: Thymus extracts for nutritional supplements are usually derived from young calves. Preliminary evidence found no improvement in HIV progression to AIDS or immunostimulation, although some immunological activity was noted in a non-randomized controlled trial. Additional study is needed in this area.
Avoid if allergic or hypersensitive to thymus extracts. Use bovine thymus extract supplements cautiously due to potential for exposure to the virus that causes "mad cow disease." Avoid use with an organ transplant or other forms of allografts or xenografts. Avoid if receiving immunosuppressive therapy or hormone therapy. Avoid with thymic tumors, myasthenia gravis (neuromuscular disorder) or untreated hypothyroidism. Avoid if pregnant or breastfeeding. Thymic extract increases human sperm motility and progression.
Traditional Chinese medicine (TCM): Traditional Chinese medicine (TCM) is a broad term that refers to many different treatments and traditions of healing. They share a common heritage of technique or theory rooted in ancient Chinese philosophy (Taoism) that dates back over 5,000 years. TCM herbs are a popular complementary therapy in HIV/AIDS. However, study results conflict. More studies are needed before the potential benefits of TCM herbs in HIV/AIDS can be established.
Chinese herbs can be potent and may interact with other herbs, foods or drugs. Consult a qualified healthcare professional before taking. There have been reports of manufactured or processed Chinese herbal products being tainted with toxins or heavy metal or not containing the listed ingredients. Herbal products should be purchased from reliable sources. Avoid ma huang, which is the active ingredient in ephedra. Avoid ginseng if pregnant or breastfeeding.
Turmeric: Turmeric is a perennial plant native to India and Indonesia, and it is often used as a spice in cooking. Several laboratory studies suggest that curcumin, a component of turmeric, may have activity against HIV. However, reliable human studies are lacking in this area.
Avoid if allergic or hypersensitive to turmeric (curcumin), yellow food colorings or plants belonging to the Curcuma or Zingiberaceae (ginger) families. Use cautiously with history of bleeding disorders, immune system deficiencies, liver disease or gallstones. Use cautiously with blood-thinners (e.g. warfarin). Use cautiously if pregnant or breastfeeding.
Vitamin A: Vitamin A is a fat-soluble vitamin, which is derived from two sources - retinoids and carotenoids. Retinoids are found in animal sources (such as the liver, kidney, eggs and dairy products). Carotenoids are found in plants like dark or yellow vegetables and carrots. The role of vitamin A in the prevention, transmission, or treatment of HIV is controversial and not well established. A clear conclusion cannot be formed based on the available scientific research.
Avoid if allergic or hypersensitive to vitamin A. Vitamin A toxicity can occur if taken at high dosages. Use cautiously with liver disease or alcoholism. Smokers who consume alcohol and beta-carotene may have an increased risk for lung cancer or heart disease. Vitamin A appears safe in pregnant women if taken at recommended doses. Use cautiously if breastfeeding because the benefits or dangers to nursing infants are not clearly established.
Zinc: Zinc formulations have been used since Ancient Egyptian times to enhance wound healing. Patients with HIV/AIDS, especially in those with low zinc levels, may benefit from zinc supplementation. Some low quality studies cite reduction in infections, enhanced weight gain and immune system function, including increased CD4 and CD8 cells. However, other low quality studies conflict with these findings. Further research is needed before a conclusion can be drawn.
Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride since studies have not been done on its safety or effectiveness. While zinc appears safe during pregnancy in amounts lower than the established upper intake level, caution should be used since studies cannot rule out the possibility of harm to the fetus.
Fair negative scientific evidence:
Ozone therapy: Ozone molecules are composed of three oxygen atoms. Ozone exists high in the earth's atmosphere and absorbs radiation from the sun. Reports of using ozone for medicinal purposes date to the late 19th Century. Laboratory studies have shown HIV virus to be sensitive to ozone, but no high-quality human studies exist. A preliminary study measured the safety and effectiveness of ozone-treated blood in the treatment of HIV infection and immune disease. Ozone therapy was not shown to enhance immune activation or diminish HIV virus.
Autohemotherapy has been associated with transmission of viral hepatitis, and with a possible case of dangerously lowered blood cell counts. Insufflation of the ear carries a risk of tympanic membrane ("ear drum") damage, and colon insufflation may increase the risk of bowel rupture. Consult a qualified health professional before undergoing any ozone-related treatment
St John's wort: St. John's wort is a perennial herb that grows up to 32 inches tall and is commonly found in many parts of the world, including eastern North America and the Pacific coast. Anti-viral effects of St. John's wort have been observed in laboratory studies, but were not found in one human study. Multiple reports of significant adverse effects and interactions with drugs used for HIV/AIDS, including protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), suggest that patients being treated for HIV/AIDS should avoid this herb. Therefore, there is evidence to recommend against using St. John's wort in the treatment of patients with HIV/AIDS.
Avoid if allergic or hypersensitive to plants in the Hypericaceae family. Rare allergic skin reactions like itchy rash have been reported. Avoid with immunosuppressant drugs (like cyclosporine, tacrolimus or myophenic acid). Avoid with non-nucleoside reverse transcriptase inhibitors or protease inhibitors. Avoid with organ transplants, suicidal symptoms or before surgery. Use cautiously with history of thyroid disorders. Use cautiously with drugs that are broken down by the liver, with monoamine oxidase inhibitors (MAOI) or selective serotonin reuptake inhibitors (SSRIS), digoxin, or birth control pills. Use cautiously with diabetes or with history of mania, hypomania or seasonal affective disorder. Avoid if pregnant or breastfeeding.

Risk factors

Age:
Older patients: The older the HIV patient, the faster he/she is likely to progress to AIDS. The effect is most apparent in patients older than 40. Researchers estimate that the risk of developing AIDS increases 27-55% every ten years.
According to a meta-analysis of 38 studies that involved more than 13,000 HIV patients, age and time since diagnosis were significant factors in determining the rate of HIV progression. Patients who developed HIV antibodies between the ages of 15 and 24 lived an average of 12.5 additional years. These patients progressed to AIDS after an average of 11 years. Patients who developed HIV antibodies between the ages of 45 and 54 lived an average of 7.9 additional years. These patients progressed to AIDS after an average of 7.7 years.
While the exact reason for this is unknown, some researchers suggest that older patients have a decreased ability to replace the CD4 T-cells that HIV infects and destroys. It is also unclear whether this is a result of the thymus gland's inability to produce new CD4 T-cells. Others suggest that older patients may have lower levels of chemokines, white blood cells that help fight off HIV.
Younger patients: HIV progression is also faster among patients who are younger than 13 years old, especially newborn babies who are born with the virus. This is likely because the newborn's immune system is not yet fully developed. Newborn babies do not begin to make their own antibodies (proteins that detect and bind to foreign substances like viruses) until they are about six months old.
Co-infections:
Cytomegalovirus (CMV): Many types of herpes viruses, including cytomegalovirus (CMV), may increase the risk of developing AIDS. Herpes viruses produce proteins that may increase the speed at which HIV replicates. Several studies have suggested that patients who have both HIV and CMV are likely to develop AIDS quicker than those who only have HIV.
However, recent research has produced conflicting results, and the role of CMV as a possible co-factor remains unknown. For instance, one study found that CMV only affected disease progression in individuals who were already diagnosed with AIDS.
Based on the theory that CMV and other herpes viruses may increase HIV replication, researchers have evaluated the effect of anti-herpes treatment in HIV patients. Based on the results of several studies, it has been suggested that high doses of the anti-herpes drug acyclovir (Zovirax?) may increase survival time in HIV patients, particularly in those who have advanced HIV. However, other studies have found no effect of acyclovir treatment on survival time in HIV patients. Further research is warranted in order to make a firm conclusion.
Hepatitis C virus (HCV): Hepatitis C virus (HCV) appears to cause a rapid progression of both HIV and HCV-related diseases. Despite modern-day antiretroviral therapy (ART), patients infected with both HIV and HCV still have a greater risk of death than those only infected with HIV.
According to recent research, HCV's impact on HIV progression varies, depending on the genetic makeup of HCV. Also, patients who are infected with several different genetic types of HCV are likely to experience even faster HIV progression. Some researchers suggest that ART may decrease the impact HCV has on HIV progression.
Herpes virus type 6: Herpes virus type 6 (HHV-6) has also been suggested as a possible factor in HIV progression. The virus infects CD4 T-cells and produces a protein that may make increase the rate at which HIV replicates inside the white blood cells. However, one study evaluated long-term non-progressed HIV patients who had herpes viruses and based on their results, the researchers suggested that HHV-6, HHV-7, and HHV-8 are not co-factors in HIV progression.
T -lymphocyte virus: According to some studies, co-infection with the retrovirus human T-lymphocyte virus type 1 (HTLV-1) may increase the risk of an HIV-infected patient developing AIDS.
Ethnicity and location:
It has been suggested that Africans living in the United Kingdom develop AIDS and die more quickly than non-Africans. However, recent research does not support this claim. According to a review of more than 1,050 HIV-infected Africans and 992 HIV-infected non-Africans diagnosed with the disease between 1982 and 1995, there was not a significant difference in survival rates between the two groups. The Africans lived an average of 82 months, while the non-Africans lived an average of 78 months. The researchers also reported no significant difference in the CD4 cell counts or rates of progression.
The researchers suggested that it was highly likely that the African patients studied were infected with a different strain of HIV (called HIV-2) than the one that normally infects homosexual men and injection-drug users in Europe and North America (called HIV-1). If HIV-2 does not cause HIV progression quicker outside of Africa, this suggests that environmental factors, such as lack of access to antiretroviral therapy (ART) and treatment for opportunistic infections, lead to the faster progression rates in Africa.
Other research suggests that HIV progression rates among individuals living in Uganda are similar to those in developed countries. The researchers estimated that the average time from HIV exposure to an AIDS diagnosis was 9.4 years.
However, some studies suggest that a common genetic mutation among Africans may increase the patient's risk of developing HIV, and increase the rate of disease progression.
Another study conducted in the United States found no difference in viral load levels (number of HIV viral particles in the blood) among different racial groups, after controlling for access to medical care, socio-economic status, and CD4 cell counts.
Gender:
Based on several studies in both adults and children, it appears that gender does not affect the risk of HIV disease progression. In general, women have a lower viral set-point than men. The viral set-point is the point at which HIV replication slows and is suppressed by the body's white blood cells. However, this lower set-point does not appear to influence the rate of HIV disease progression.
Genetics:
Receptors: Patients who have certain genetic mutations or variations may have CD4 cells that are either more or less susceptible to HIV infection. This may occur in patients who either lack the co-receptors CCR5 or CXCR4, or they express them in a different way.
For instance, one meta-analysis found that a variation of the CCR5 co-receptor, called CCR5-?"32, reduced the risk of HIV patients developing AIDS by 31%, and lowered the risk of death by 39%.
Another study showed that patients who had mutations on their CCR5 receptors called 356T were more susceptible to HIV infection. This mutation, according to researchers, may also increase the rate of disease progression.
Chemical messengers: Genetic variation in chemical messengers called cytokines and chemokines may also impact the rate of HIV progression. These chemical messengers signal the white blood cells to move towards an area of infection. According to one study that evaluated 337 slow and fast progressors, genetic variations of two types of cytokines called interleukin-4 and interleukin-10 led to an increased rate of disease progression.
In addition, a low copy number of the gene for a chemokine called CCL3L1 has been associated with a significantly increased risk of HIV progression.
Human leukocyte antigens (HLA): Researchers have also demonstrated a relationship between the genetic makeup of human leukocyte antigens (HLA) and HIV progression. HLA are proteins found in the membranes (outside surface) of nearly every cell in the body. These antigens are found in especially high concentrations on the surface of white blood cells. In healthy individuals, HLA antigens help the body's immune system distinguish between self and non-self (foreign or invading) substances.
Several studies suggest that a diverse range of HLA variations decreases the rate of HIV disease progression. Researchers have discovered that HIV adapts to the most frequent HLA genes in the body. Therefore, individuals who have rare gene types usually have a slower disease progression.
Specific genes that are associated with slow or rapid HIV progression have been identified. According to researchers, patients who have HLA class I genes A1, B14, B44, B27, B5701, and C8 are more likely to experience slow or non-progressive HIV, while patients who have HLA class I genes A29, B22, B54, B55, and B56 are more likely to experience rapid progression.
Researchers have not yet discovered exactly how HLA affects HIV progression. It has been suggested that HLA molecules directly limit HIV's ability to replicate. Other researchers suggest that the HLA molecules that are associated with slow progression may help the immune cells identify HIV quicker and help stimulate a more rapid immune response.
Multi-drug transporter gene: The multi-drug resistance transporter 1 (MDR1) gene has been associated with an increased risk of rapid HIV progression. However, the scientific evidence of this association is controversial.
The MDR1 gene produces P-glycoprotein (P-gp), which is a drug transport molecule that protects the body's cells from toxic chemicals like HIV antiretrovirals by removing them from the cells.
While some researchers suggest that P-gp may influence how susceptible a patient's immune cells are to HIV infection, the results of a new study do not support this claim. The researchers evaluated the type and amount of MDR1 in the T-cells of HIV-negative subjects. The cells were then exposed to HIV in the laboratory. MDR1 and P-gp did not influence the cells' vulnerability to HIV infection.
Other: The human protein called APOBEC3G is an antiviral protein that prevents HIV from replicating inside the body. The protein changes HIV's DNA molecules, which inhibits viral replication. However, HIV produces viral infectivity factor (Vif), which inhibits APOBEC3G's activity.
According to one study that evaluated more than 3,070 HIV patients, variations in the APOBEC3G gene may influence the rate of HIV disease progression. The researchers found that one variant called H186R, common among African Americans, was associated with a rapid drop in CD4 cell counts.
Infection route:
It has been suggested that infection route (how the disease was transmitted) may impact the rate of HIV progression in patients. For instance, HIV can be spread by sexual contact with an infected person, by sharing needles/syringes with someone who is infected, through breastfeeding, during vaginal birth or, less commonly (and rare in countries where blood is screened for HIV antibodies), through transfusions with infected blood. However, research results are conflicting.
Some studies have found faster rates of disease progression among HIV-infected patients who were infected via blood transfusion. However these studies may not have considered the age of the blood transfusion recipients. Patients who are infected at an older age are more likely to experience a faster disease progression.
While it has also been suggested that patients who acquire the disease via injection-drug use are more likely to experience a faster disease progression, there is conflicting scientific evidence. More studies are necessary before any firm conclusions can be made.
Nutrition:
According to several studies, patients who have deficient levels of vitamin A, vitamin B12, or zinc are more likely to experience a rapid decline of CD4 cell counts. This is because the body's white blood cells need sufficient levels of these vitamins in order to grow and maintain health.
Researchers believe that poor absorption of nutrients, diarrhea, and inadequate calorie and protein consumption contribute to HIV progression. For instance, researchers found that poor nutrition in Zambia was the best predictor of death in both HIV-negative and HIV-positive children.
Several studies have shown that multivitamin supplementation can slow the rate of HIV disease progression and death. However, HIV patients who have gastrointestinal problems may have a difficult time absorbing these essential vitamins into the bloodstream. Some HIV patients may need to take vitamins that are injected or in a form that will dissolve in the mouth and be absorbed across the mucus membranes.
Pregnancy:
The majority of studies suggest that pregnancy does not increase the rate of HIV disease progression. However, there is scientific evidence that the patient's viral load (number of HIV viral particles in the blood) increases gradually from delivery until 12 weeks after delivery, even in women receiving consistent antiretroviral therapy.
Recreational drug use:
The majority of studies suggest that recreational drug use does not play a role in HIV disease progression. However, some studies are contradictory.
According to one study involving nearly 1,150 HIV-positive women (40% of whom used cocaine, heroin, methadone, or injection-drugs), there appears to be no association between drug use and CD4 cell percentage, viral loads, or death (of any cause). However, HIV patients who used drugs were more likely to develop other infections, especially herpes, tuberculosis, and recurrent pneumonia. Patients who develop these infections may then have an increased risk of progressing to AIDS.
Alcohol: Alcohol abuse appears to be prevalent among HIV patients. One study found that 41% of HIV-infected patients met the criteria for alcoholism, as defined by a score of five or higher on the Michigan Alcoholism Screening Test (MAST) survey. Recent studies have shown that HIV-infected patients with a history of alcohol problems, who are receiving highly active antiretroviral therapy (HAART) and are currently drinking, have greater HIV progression than those who do not drink.
In vitro studies suggest that Alcohol may block a chemical messenger in the immune system and stimulate the expression of CCR5 co-receptor, which HIV uses to infect cells. This in turn may lead to increased rates of HIV replication. However, human studies have not shown an association between alcohol consumption and HIV progression.
Cocaine: Cocaine use may affect HIV disease progression either directly or indirectly. Some studies have suggested that cocaine may increase the rate of HIV replication and suppress cytokines (chemical messenger that stimulate the immune response). These factors may enable HIV to infect more immune system cells.
Inhaled nitrates (poppers): It has been suggested that inhaled nitrates (poppers) may suppress the immune system. However, human and animal studies that have evaluated this association have produced inconclusive results. Further research is necessary to fully understand the relationship between inhaled nitrates and HIV.
Injection-drug use: Some researchers believe that DNA damage caused by injection-drug use may result in faster HIV replication and greater potential for viral mutations. This may ultimately lead to an increased risk of developing neurological diseases and resistance to antiretroviral drugs. However, more research is necessary to verify these claims.
HIV patients sharing needles may re-expose themselves to HIV, which may increase the rate of HIV disease progression. These patients also have an increased risk of developing other infections.
Marijuana: Marijuana may aggravate symptoms of HIV-induced mental impairment, especially memory loss, in patients who have advanced HIV.
Methamphetamine (meth): Methamphetamine (meth) may increase the risk of HIV disease progression. According to the results of one study, methamphetamine users who were receiving antiretroviral therapy (ART) were more likely to have higher viral loads than non-users. However, there appeared to be no significant difference in methamphetamine users who did not receive antiretroviral therapy. The researchers concluded that the impact on viral load may be the result of poor treatment adherence rather than a direct affect of the drug.
Researchers have found that both methamphetamine abuse and HIV infection may cause impaired cognitive (mental) functions. Patients may experience difficulties learning new information, solving problems, concentrating and quickly processing information. The researchers suggest that methamphetamine abuse and HIV infection significantly reduce the size of certain brain structures, which may be associated with impaired cognitive functions. Co-occurring methamphetamine abuse and HIV infection has shown to cause a greater impairment than each condition alone.
Repeated exposure to HIV:
There is some scientific evidence suggesting that repeated exposure to HIV increases the rate of HIV disease progression.
One study involving 937 HIV-infected men who received little or no antiretroviral therapy found that the patients who had unprotected receptive anal intercourse experienced more rapid declines in their CD4 cell counts than men who did not engage in unprotected sex. The men who reported having unprotected sex in the last year were twice as likely to experience a CD4 cell drop as those who did not. The researchers found that the more people the patient had unprotected, receptive anal sex with, the greater the risk of CD4 cell count decline. However, the researchers could not determine whether the CD4 cell count decrease was the result of re-infection with HIV or exposure to other sexually transmitted infections or diseases.
Smoking:
The majority of studies suggest that smoking does not influence the rate of HIV disease progression. However, there is good scientific evidence that HIV patients who smoke tobacco are more likely to develop certain opportunistic infections and diseases. Opportunistic infections occur in individuals who have weakened immune systems.
Candidiasis (thrush): In general, smokers are more likely to develop a yeast infection of the mouth called oral candidiasis (thrush) than non-smokers. More research is necessary to determine whether the same is true for HIV-positive patients.
One study found that even though smoking increased the amount of Candida albicans (yeast that causes the disease) in the mouths of HIV patients, it did not appear to increase the risk of developing thrush.
Another study found that smoking increased the risk of developing thrush, bacterial pneumonia, and another mouth infection called oral hairy leukoplakia in HIV-positive men. Patients who smoked the most had the greatest risk of developing these infections.
Emphysema: In addition, smokers who have HIV are more likely to develop emphysema than non-smokers. Emphysema is a chronic lung disease characterized by shortness of breath. Researchers conducted a study involving HIV-positive and HIV-negative people who smoked for 12 years or more. The researchers found that 37% of the HIV-positive patients showed evidence of emphysema, while none of the HIV-negative patients had signs or symptoms of the disease. HIV-positive patients also had higher levels of cytotoxic CD8 T-cells in their lungs tissues indicating that these immune cells may have caused some of the lung damage.
Kidney disease: Some research suggests that HIV patients who smoke are more likely to develop kidney disease than those who do not.
Lung cancer: HIV patients who smoke tobacco are more likely to develop lung cancer than HIV patients who do not. This is because the smoke contains more than 4,000 different chemicals and many of these chemicals have been shown to be cancer-causing substances.
Lung infection: Smokers typically have slightly higher CD4 cell counts than non-smokers. However, analyses of immune cells in the lung fluid show that the CD4 and CD8 percentages and cytokine activity are significantly lower in smokers than non-smokers. Therefore, smokers have an increased risk of developing lung infections. For instance, a review of 598 HIV patients found that smokers were three times more likely to develop Pneumocystis jiroveci pneumonia (formerly called Pneumocystis carinii pneumonia or PCP) than non-smokers. Patients who smoked the most were at the greatest risk of developing lung infections.
Smoking and pregnancy: HIV-infected pregnant women who smoke may have a greater chance of transmitting the disease to their babies during vaginal delivery, according to one study. However, the study was conducted between 1988 and 1990, before antiretroviral therapy was introduced as a treatment during pregnancy. Currently, antiretroviral therapy is given to pregnant women to reduce the risk of passing the disease. One-third of the patients who smoked in the study transmitted HIV to their babies, compared to less than one-fourth of women who did not smoke. Researchers have suggested that nicotine may cause the membranes surrounding the fetus to rupture prematurely, which increases the time the infant may be exposed to HIV-infected blood during delivery.
Stress:
According to researchers, severe stress can increase the rate of HIV disease progression. Patients who had severe and frequent stress over a two-year period were four times more likely to experience HIV disease progression, according to one study. However, levels of stress that are common to everyday life did not affect the rate of disease progression.
In addition, psychological distress has also shown to increase the rate of HIV disease progression, but did not lead to a shorter survival time, according to one cohort study. The researchers concluded that patients who experienced psychological distress were more likely to develop an AIDS-defining illness within two years. When HIV patients develop an AIDS-defining illness, this means their condition has progressed to AIDS.
Experience of healthcare providers:
Studies have shown that patients who receive medical care from healthcare providers who have experience in treating HIV and AIDS patients are more likely to live longer than those who receive care from less-experienced doctors. One study found that AIDS patients who received care from the most experienced doctors were 43% more likely to survive than patients who received care from the least-experienced doctors.
Another study, conducted by the same researcher, found that patients who received care from experienced healthcare providers were more likely to receive primary care and special services, as well as better access to laboratory and pharmacy services.