AIDS
From Wikipedia, the free encyclopedia
| The Red ribbon is a symbol for solidarity with HIV-positive people and those living with AIDS. | |
| ICD-10 | B24. |
| ICD-9 | 042 |
| DiseasesDB | 5938 |
| MedlinePlus | 000594 |
| eMedicine | emerg/253 |
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome (AIDS or Aids) is a collection of symptoms and infections in humans resulting from the specific damage to the immune system caused by the human immunodeficiency virus (HIV).<ref name=Marx>Marx, J. L. (1982). "New disease baffles medical community". Science 217 (4560): 618-621. PubMed.</ref> The late stage of the condition leaves individuals prone to opportunistic infections and tumors. Although treatments for AIDS and HIV exist to slow the virus's progression, there is no known cure. HIV is transmitted through direct contact of a mucous membrane or the bloodstream with a bodily fluid containing HIV, such as blood, semen, vaginal fluid, preseminal fluid, and breast milk.<ref name=CDCtransmission>Divisions of HIV/AIDS Prevention (2003). HIV and Its Transmission. Centers for Disease Control & Prevention. Retrieved on 2006-05-23.</ref><ref name=sfaf>San Francisco AIDS Foundation (2006-04-14). How HIV is spread. Retrieved on 2006-05-23.</ref> This transmission can come in the form of anal, vaginal or oral sex, blood transfusion, contaminated hypodermic needles, exchange between mother and baby during pregnancy, childbirth, or breastfeeding, or other exposure to one of the above bodily fluids.
Most researchers believe that HIV originated in sub-Saharan Africa during the twentieth century;<ref name=Gao>
Gao, F., Bailes, E., Robertson, D. L., Chen, Y., Rodenburg, C. M., Michael, S. F., Cummins, L. B., Arthur, L. O., Peeters, M., Shaw, G. M., Sharp, P. M. and Hahn, B. H. (1999). "Origin of HIV-1 in the Chimpanzee Pan troglodytes troglodytes". Nature 397 (6718): 436-441. PubMed DOI:10.1038/17130.</ref> it is now a pandemic, with an estimated 38.6 million people now living with the disease worldwide.<ref name=UNAIDS2006>UNAIDS (2006). “Overview of the global AIDS epidemic”, 2006 Report on the global AIDS epidemic (PDF). Retrieved on 2006-06-08.</ref> As of January 2006, the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization (WHO) estimate that AIDS has killed more than 25 million people since it was first recognized on June 5, 1981, making it one of the most destructive epidemics in recorded history. In 2005 alone, AIDS claimed an estimated 2.4–3.3 million lives, of which more than 570,000 were children.<ref name=UNAIDS2006 /> A third of these deaths are occurring in sub-Saharan Africa, retarding economic growth and destroying human capital. Antiretroviral treatment reduces both the mortality and the morbidity of HIV infection, but routine access to antiretroviral medication is not available in all countries.<ref name=Palella>Palella, F. J. Jr, Delaney, K. M., Moorman, A. C., Loveless, M. O., Fuhrer, J., Satten, G. A., Aschman and D. J., Holmberg, S. D. (1998). "Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators". N. Engl. J. Med 338 (13): 853-860. PubMed.</ref> HIV/AIDS stigma is more severe than that associated with other life-threatening conditions and extends beyond the disease itself to providers and even volunteers involved with the care of people living with HIV.
Contents |
[edit] Infection by HIV
- For more details on this topic, see HIV.
AIDS is the most severe manifestation of infection with HIV. HIV is a retrovirus that primarily infects vital components of the human immune system such as CD4+ T cells (a subset of T cells), macrophages and dendritic cells. It directly and indirectly destroys CD4+ T cells. CD4+ T cells are required for the proper functioning of the immune system. When HIV kills CD4+ T cells so that there are fewer than 200 CD4+ T cells per microliter (µL) of blood, cellular immunity is lost, leading to the condition known as AIDS. Acute HIV infection progresses over time to clinical latent HIV infection and then to early symptomatic HIV infection and later to AIDS, which is identified on the basis of the amount of CD4+ T cells in the blood and the presence of certain infections.
In the absence of antiretroviral therapy, the median time of progression from HIV infection to AIDS is nine to ten years, and the median survival time after developing AIDS is only 9.2 months.<ref name=Morgan2>Morgan, D., Mahe, C., Mayanja, B., Okongo, J. M., Lubega, R. and Whitworth, J. A. (2002). "HIV-1 infection in rural Africa: is there a difference in median time to AIDS and survival compared with that in industrialized countries?". AIDS 16 (4): 597-632. PubMed.</ref> However, the rate of clinical disease progression varies widely between individuals, from two weeks up to 20 years. Many factors affect the rate of progression. These include factors that influence the body's ability to defend against HIV such as the infected person's general immune function.<ref name=Clerici>Clerici, M., Balotta, C., Meroni, L., Ferrario, E., Riva, C., Trabattoni, D., Ridolfo, A., Villa, M., Shearer, G.M., Moroni, M. and Galli, M. (1996). "Type 1 cytokine production and low prevalence of viral isolation correlate with long-term non progression in HIV infection". AIDS Res. Hum. Retroviruses. 12 (11): 1053-1061. PubMed.</ref><ref name=Morgan>Morgan, D., Mahe, C., Mayanja, B. and Whitworth, J. A. (2002). "Progression to symptomatic disease in people infected with HIV-1 in rural Uganda: prospective cohort study". BMJ 324 (7331): 193-196. PubMed.</ref> Older people have weaker immune systems, and therefore have a greater risk of rapid disease progression than younger people. Poor access to health care and the existence of coexisting infections such as tuberculosis also may predispose people to faster disease progression.<ref name=Morgan2 /><ref name=Gendelman>Gendelman, H. E., Phelps, W., Feigenbaum, L., Ostrove, J. M., Adachi, A., Howley, P. M., Khoury, G., Ginsberg, H. S. and Martin, M. A. (1986). "Transactivation of the human immunodeficiency virus long terminal repeat sequences by DNA viruses". Proc. Natl. Acad. Sci. U. S. A. 83 (24): 9759-9763. PubMed.</ref><ref name=Bentwich>Bentwich, Z., Kalinkovich., A. and Weisman, Z. (1995). "Immune activation is a dominant factor in the pathogenesis of African AIDS.". Immunol. Today 16 (4): 187-191. PubMed.</ref> The infected person's genetic inheritance plays an important role and some people are resistant to certain strains of HIV.<ref name=Tang>Tang, J. and Kaslow, R. A. (2003). "The impact of host genetics on HIV infection and disease progression in the era of highly active antiretroviral therapy". AIDS 17 (Suppl 4): S51-S60. PubMed.</ref> An example of this is people with the CCR5-Δ32 mutation are resistant to infection with certain strains of HIV. HIV is genetically variable and exists as different strains, which cause different rates of clinical disease progression.<ref name=Quinones>Quiñones-Mateu, M. E., Mas, A., Lain de Lera, T., Soriano, V., Alcami, J., Lederman, M. M. and Domingo, E. (1998). "LTR and tat variability of HIV-1 isolates from patients with divergent rates of disease progression". Virus Research 57 (1): 11-20. PubMed.</ref><ref name=Campbell>Campbell, G. R., Pasquier, E., Watkins, J., Bourgarel-Rey, V., Peyrot, V., Esquieu, D., Barbier, P., de Mareuil, J., Braguer, D., Kaleebu, P., Yirrell, D. L. and Loret E. P. (2004). "The glutamine-rich region of the HIV-1 Tat protein is involved in T-cell apoptosis". J. Biol. Chem. 279 (46): 48197-48204. PubMed.</ref><ref name=Kaleebu>Kaleebu P, French N, Mahe C, Yirrell D, Watera C, Lyagoba F, Nakiyingi J, Rutebemberwa A, Morgan D, Weber J, Gilks C, Whitworth J. (2002). "Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression in a large cohort of HIV-1-positive persons in Uganda". J. Infect. Dis. 185 (9): 1244-1250. PubMed.</ref> The use of highly active antiretroviral therapy prolongs both the median time of progression to AIDS and the median survival time.
[edit] Diagnosis
Since June 5, 1981, many definitions have been developed for epidemiological surveillance such as the Bangui definition and the 1994 expanded World Health Organization AIDS case definition. However, clinical staging of patients was not an intended use for these systems as they are neither sensitive, nor specific. In developing countries, the World Health Organization staging system for HIV infection and disease, using clinical and laboratory data, is used and in developed countries, the Centers for Disease Control (CDC) Classification System is used.
[edit] WHO disease staging system for HIV infection and disease
In 1990, the World Health Organization (WHO) grouped these infections and conditions together by introducing a staging system for patients infected with HIV-1.<ref name=WHO>World Health Organization (1990). "Interim proposal for a WHO staging system for HIV infection and disease". WHO Wkly Epidem. Rec. 65 (29): 221-228. PubMed.</ref> An update took place in September 2005. Most of these conditions are opportunistic infections that are easily treatable in healthy people.
- Stage I: HIV disease is asymptomatic and not categorized as AIDS
- Stage II: includes minor mucocutaneous manifestations and recurrent upper respiratory tract infections
- Stage III: includes unexplained chronic diarrhea for longer than a month, severe bacterial infections and pulmonary tuberculosis
- Stage IV: includes toxoplasmosis of the brain, candidiasis of the esophagus, trachea, bronchi or lungs and Kaposi's sarcoma; these diseases are indicators of AIDS.
[edit] CDC classification system for HIV infection
The Centers for Disease Control and Prevention (CDC) originally classified AIDS as GRID which stood for Gay Related Immune Disease. However, after determining that AIDS is not isolated to homosexual people the name was changed to the neutral AIDS. In 1993, the CDC expanded their definition of AIDS to include all HIV positive people with a CD4+ T cell count below 200 per µL of blood or 14% of all lymphocytes.<ref name=MMWR>CDC (1992). 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults. CDC. Retrieved on 2006-02-09.</ref> The majority of new AIDS cases in developed countries use either this definition or the pre-1993 CDC definition. The AIDS diagnosis still stands even if, after treatment, the CD4+ T cell count rises to above 200 per µL of blood or other AIDS-defining illnesses are cured.
[edit] HIV test
Many people are unaware that they are infected with HIV.<ref name=Kumaranayake>
Kumaranayake, L. and Watts, C. (2001). "Resource allocation and priority setting of HIV/AIDS interventions: addressing the generalized epidemic in sub-Saharan Africa". J. Int. Dev. 13 (4): 451-466. DOI:10.1002/jid.798.</ref> Less than 1% of the sexually active urban population in Africa has been tested, and this proportion is even lower in rural populations. Furthermore, only 0.5% of pregnant women attending urban health facilities are counseled, tested or receive their test results. Again, this proportion is even lower in rural health facilities.<ref name=Kumaranayake>
Kumaranayake, L. and Watts, C. (2001). "Resource allocation and priority setting of HIV/AIDS interventions: addressing the generalized epidemic in sub-Saharan Africa". J. Int. Dev. 13 (4): 451-466. DOI:10.1002/jid.798.</ref> Therefore, donor blood and blood products used in medicine and medical research are screened for HIV. Typical HIV tests, including the HIV enzyme immunoassay and the Western blot assay, detect HIV antibodies in serum, plasma, oral fluid, dried blood spot or urine of patients. However, the window period (the time between initial infection and the development of detectable antibodies against the infection) can vary. This is why it can take 3-6 months to seroconvert and test positive. Commercially available tests to detect other HIV antigens, HIV-RNA, and HIV-DNA in order to detect HIV infection prior to the development of detectable antibodies are available. For the diagnosis of HIV infection these assays are not specifically approved, but are nonetheless routinely used in developed countries.
[edit] Symptoms and complications
The symptoms of AIDS are primarily the result of conditions that do not normally develop in individuals with healthy immune systems. Most of these conditions are infections caused by bacteria, viruses, fungi and parasites that are normally controlled by the elements of the immune system that HIV damages. Opportunistic infections are common in people with AIDS.<ref name=Holmes>Holmes, C. B., Losina, E., Walensky, R. P., Yazdanpanah, Y., Freedberg, K. A. (2003). "Review of human immunodeficiency virus type 1-related opportunistic infections in sub-Saharan Africa". Clin. Infect. Dis. 36 (5): 656-662. PubMed.</ref> HIV affects nearly every organ system. People with AIDS also have an increased risk of developing various cancers such as Kaposi's sarcoma, cervical cancer and cancers of the immune system known as lymphomas.
Additionally, people with AIDS often have systemic symptoms of infection like fevers, sweats (particularly at night), swollen glands, chills, weakness, and weight loss.<ref name=Guss>Guss, D. A. (1994). "The acquired immune deficiency syndrome: an overview for the emergency physician, Part 1". J. Emerg. Med. 12 (3): 375-384. PubMed.</ref><ref name=Guss2>Guss, D. A. (1994). "The acquired immune deficiency syndrome: an overview for the emergency physician, Part 2". J. Emerg. Med. 12 (4): 491-497. PubMed.</ref> After the diagnosis of AIDS is made, the current average survival time with antiretroviral therapy (as of 2005) is estimated to be more than 5 years,<ref name=Schneider>Schneider, M. F., Gange, S. J., Williams, C. M., Anastos, K., Greenblatt, R. M., Kingsley, L., Detels, R., and Munoz, A. (2005). "Patterns of the hazard of death after AIDS through the evolution of antiretroviral therapy: 1984-2004". AIDS 19 (17): 2009-2018. PubMed.</ref> but because new treatments continue to be developed and because HIV continues to evolve resistance to treatments, estimates of survival time are likely to continue to change. Without antiretroviral therapy, death normally occurs within a year.<ref name=Morgan2 /> Most patients die from opportunistic infections or malignancies associated with the progressive failure of the immune system.<ref name=Lawn>Lawn, S. D. (2004). "AIDS in Africa: the impact of coinfections on the pathogenesis of HIV-1 infection". J. Infect. Dis. 48 (1): 1-12. PubMed.</ref>
The rate of clinical disease progression varies widely between individuals and has been shown to be affected by many factors such as host susceptibility and immune function<ref name=Clerici /><ref name=Morgan /><ref name=Tang /> health care and co-infections,<ref name=Morgan2 /><ref name=Lawn /> as well as factors relating to the viral strain.<ref name=Campbell /><ref name=Campbell2>Campbell, G. R., Watkins, J. D., Esquieu, D., Pasquier, E., Loret, E. P. and Spector, S. A. (2005). "The C terminus of HIV-1 Tat modulates the extent of CD178-mediated apoptosis of T cells". J. Biol. Chem. 280 (46): 38376-39382. PubMed.</ref><ref name=Senkaali>Senkaali, D., Muwonge, R., Morgan, D., Yirrell, D., Whitworth, J. and Kaleebu, P. (2005). "The relationship between HIV type 1 disease progression and V3 serotype in a rural Ugandan cohort". AIDS Res. Hum. Retroviruses. 20 (9): 932-937. PubMed.</ref> The specific opportunistic infections that AIDS patients develop depend in part on the prevalence of these infections in the geographic area in which the patient lives.
[edit] Major pulmonary illnesses
- Pneumocystis jiroveci pneumonia (originally known as Pneumocystis carinii pneumonia, often-abbreviated PCP) is relatively rare in healthy, immunocompetent people, but common among HIV-infected individuals. Before the advent of effective diagnosis, treatment and routine prophylaxis in Western countries, it was a common immediate cause of death. In developing countries, it is still one of the first indications of AIDS in untested individuals, although it does not generally occur unless the CD4 count is less than 200 per µL.<ref name=Feldman>Feldman, C. (2005). "Pneumonia associated with HIV infection". Curr. Opin. Infect. Dis. 18 (2): 165-170. PubMed.</ref>
- Tuberculosis (TB) is unique among infections associated with HIV because it is transmissible to immunocompetent people via the respiratory route, is easily treatable once identified, may occur in early-stage HIV disease, and is preventable with drug therapy. However, multidrug resistance is a potentially serious problem. Even though its incidence has declined because of the use of directly observed therapy and other improved practices in Western countries, this is not the case in developing countries where HIV is most prevalent. In early-stage HIV infection (CD4 count >300 cells per µL), TB typically presents as a pulmonary disease. In advanced HIV infection, TB often presents atypically with extrapulmonary (systemic) disease a common feature. Symptoms are usually constitutional and are not localized to one particular site, often affecting bone marrow, bone, urinary and gastrointestinal tracts, liver, regional lymph nodes, and the central nervous system.<ref name=Decker>Decker, C. F. and Lazarus, A. (2000). "Tuberculosis and HIV infection. How to safely treat both disorders concurrently". Postgrad Med. 108 (2): 57-60, 65-68. PubMed.</ref> Alternatively, symptoms may relate more to the site of extrapulmonary involvement.
[edit] Major gastro-intestinal illnesses
- Esophagitis is an inflammation of the lining of the lower end of the esophagus (gullet or swallowing tube leading to the stomach). In HIV infected individuals, this is normally due to fungal (candidiasis) or viral (herpes simplex-1 or cytomegalovirus) infections. In rare cases, it could be due to mycobacteria.<ref name=Zaidi>Zaidi, S. A. and Cervia, J. S. (2002). "Diagnosis and management of infectious esophagitis associated with human immunodeficiency virus infection". J. Int. Assoc. Physicians AIDS Care (Chic Ill) 1 (2): 53-62. PubMed.</ref>
- Unexplained chronic diarrhea in HIV infection is due to many possible causes, including common bacterial (Salmonella, Shigella, Listeria, Campylobacter, or Escherichia coli) and parasitic infections, and uncommon opportunistic infections such as cryptosporidiosis, microsporidiosis, Mycobacterium avium complex (MAC) and cytomegalovirus (CMV) colitis. In some cases, diarrhea may be a side effect of several drugs used to treat HIV, or it may simply accompany HIV infection, particularly during primary HIV infection. It may also be a side effect of antibiotics used to treat bacterial causes of diarrhea (common for Clostridium difficile). In the later stages of HIV infection, diarrhea is thought to be a reflection of changes in the way the intestinal tract absorbs nutrients, and may be an important component of HIV-related wasting.<ref name=Guerrant>Guerrant, R. L., Hughes, J. M., Lima, N. L., Crane, J. (1990). "Diarrhea in developed and developing countries: magnitude, special settings, and etiologies". Rev. Infect. Dis. 12 (Suppl 1): S41-S50. PubMed.</ref>
[edit] Major neurological illnesses
- Toxoplasmosis is a disease caused by the single-celled parasite called Toxoplasma gondii; it usually infects the brain causing toxoplasma encephalitis but it can infect and cause disease in the eyes and lungs.<ref name=Luft>Luft, B. J. and Chua, A. (2000). "Central Nervous System Toxoplasmosis in HIV Pathogenesis, Diagnosis, and Therapy". Curr. Infect. Dis. Rep. 2 (4): 358-362. PubMed.</ref>
- Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease, in which the gradual destruction of the myelin sheath covering the axons of nerve cells impairs the transmission of nerve impulses. It is caused by a virus called JC virus which occurs in 70% of the population in latent form, causing disease only when the immune system has been severely weakened, as is the case for AIDS patients. It progresses rapidly, usually causing death within months of diagnosis.<ref name=Sadler>Sadler, M. and Nelson, M. R. (1997). "Progressive multifocal leukoencephalopathy in HIV". Int. J. STD AIDS 8 (6): 351-357. PubMed.</ref>
- AIDS dementia complex (ADC) is a metabolic encephalopathy induced by HIV infection and fueled by immune activation of HIV infected brain macrophages and microglia which secrete neurotoxins of both host and viral origin.<ref name=Gray>Gray, F., Adle-Biassette, H., Chrétien, F., Lorin de la Grandmaison, G., Force, G., Keohane, C. (2001). "Neuropathology and neurodegeneration in human immunodeficiency virus infection. Pathogenesis of HIV-induced lesions of the brain, correlations with HIV-associated disorders and modifications according to treatments". Clin. Neuropathol. 20 (4): 146-155. PubMed.</ref> Specific neurological impairments are manifested by cognitive, behavioral, and motor abnormalities that occur after years of HIV infection and is associated with low CD4+ T cell levels and high plasma viral loads. Prevalence is 10-20% in Western countries<ref name=Grant>Grant, I., Sacktor, H., and McArthur, J. (2005). “HIV neurocognitive disorders”, H. E. Gendelman, I. Grant, I. Everall, S. A. Lipton, and S. Swindells. (ed.): The Neurology of AIDS (PDF), 2nd, London, UK: Oxford University Press, 357-373. ISBN 0-19-852610-5.</ref> but only 1-2% of HIV infections in India.<ref name=Satischandra>Satishchandra, P., Nalini, A., Gourie-Devi, M., Khanna, N., Santosh, V., Ravi, V., Desai, A., Chandramuki, A., Jayakumar, P. N., and Shankar, S. K. (2000). "Profile of neurologic disorders associated with HIV/AIDS from Bangalore, south India (1989-96)". Indian J. Med. Res. 11: 14-23. PubMed.</ref><ref name=Wadia>Wadia, R. S., Pujari, S. N., Kothari, S., Udhar, M., Kulkarni, S., Bhagat, S., and Nanivadekar, A. (2001). "Neurological manifestations of HIV disease". J. Assoc. Physicians India 49: 343-348. PubMed.</ref> This difference is possibly due to the HIV subtype in India.
- Cryptococcal meningitis is an infection of the meninx (the membrane covering the brain and spinal cord) by the fungus Cryptococcus neoformans. It can cause fevers, headache, fatigue, nausea, and vomiting. Patients may also develop seizures and confusion; left untreated, it can be lethal.
[edit] Major HIV-associated malignancies
Patients with HIV infection have substantially increased incidence of several malignant cancers. This is primarily due to co-infection with an oncogenic DNA virus, especially Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human papillomavirus (HPV).<ref name=Boshoff>Boshoff, C. and Weiss, R. (2002). "AIDS-related malignancies". Nat. Rev. Cancer 2 (5): 373-382. PubMed.</ref><ref name=Yarchoan>Yarchoan, R., Tosatom G. and Littlem R. F. (2005). "Therapy insight: AIDS-related malignancies - the influence of antiviral therapy on pathogenesis and management". Nat. Clin. Pract. Oncol. 2 (8): 406-415. PubMed.</ref> The following confer a diagnosis of AIDS when they occur in an HIV-infected person.
- Kaposi's sarcoma (KS) is the most common tumor in HIV-infected patients. The appearance of this tumor in young homosexual men in 1981 was one of the first signals of the AIDS epidemic. Caused by a gammaherpes virus called Kaposi's sarcoma-associated herpes virus (KSHV), it often appears as purplish nodules on the skin, but can affect other organs, especially the mouth, gastrointestinal tract, and lungs.
- High-grade B cell lymphomas such as Burkitt's lymphoma, Burkitt's-like lymphoma, diffuse large B-cell lymphoma (DLBCL), and primary central nervous system lymphoma present more often in HIV-infected patients. These particular cancers often foreshadow a poor prognosis. In some cases these lymphomas are AIDS-defining. Epstein-Barr virus (EBV) or KSHV cause many of these lymphomas.
- Cervical cancer in HIV-infected women is considered AIDS-defining. It is caused by human papillomavirus (HPV).
In addition to the AIDS-defining tumors listed above, HIV-infected patients are at increased risk of certain other tumors, such as Hodgkin's disease and anal and rectal carcinomas. However, the incidence of many common tumors, such as breast cancer or colon cancer, does not increase in HIV-infected patients. In areas where HAART is extensively used to treat AIDS, the incidence of many AIDS-related malignancies has decreased, but at the same time malignant cancers overall have become the most common cause of death of HIV-infected patients.<ref name=Bonnet>Bonnet, F., Lewden, C., May, T., Heripret, L., Jougla, E., Bevilacqua, S., Costagliola, D., Salmon, D., Chene, G. and Morlat, P. (2004). "Malignancy-related causes of death in human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy". Cancer 101 (2): 317-324. PubMed.</ref>
[edit] Other opportunistic infections
AIDS patients often develop opportunistic infections that present with non-specific symptoms, especially low-grade fevers and weight loss. These include infection with Mycobacterium avium-intracellulare and cytomegalovirus (CMV). CMV can cause colitis, as described above, and CMV retinitis can cause blindness. Penicilliosis due to Penicillium marneffei is now the third most common opportunistic infection (after extrapulmonary tuberculosis and cryptococcosis) in HIV-positive individuals within the endemic area of Southeast Asia.<ref name=Skoulidis>Skoulidis, F., Morgan, M. S., and MacLeod, K. M. (2004). "Penicillium marneffei: a pathogen on our doorstep?". J. R. Soc. Med. 97 (2): 394-396. PubMed.</ref>
[edit] Transmission and prevention
| Exposure Route | Estimated infections per 10,000 exposures to an infected source | |||
|---|---|---|---|---|
| Blood Transfusion | 9,000<ref name=Donegan>Donegan, E., Stuart, M., Niland, J. C., Sacks, H. S., Azen, S. P., Dietrich, S. L., Faucett, C., Fletcher, M. A., Kleinman, S. H., Operskalski, E. A., et al. (1990). "Infection with human immunodeficiency virus type 1 (HIV-1) among recipients of antibody-positive blood donations". Ann. Intern. Med. 113 (10): 733-739. PubMed.</ref> | |||
| Childbirth | 2,500<ref name=Coovadia>Coovadia, H. (2004). "Antiretroviral agents—how best to protect infants from HIV and save their mothers from AIDS". N. Engl. J. Med. 351 (3): 289-292. PubMed.</ref> | |||
| Needle-sharing injection drug use | 67<ref name=Kaplan>Kaplan, E. H. and Heimer, R. (1995). "HIV incidence among New Haven needle exchange participants: updated estimates from syringe tracking and testing data". J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 10 (2): 175-176. PubMed.</ref> | |||
| Receptive anal intercourse* | 50<ref name=ESG>European Study Group on Heterosexual Transmission of HIV (1992). "Comparison of female to male and male to female transmission of HIV in 563 stable couples". BMJ. 304 (6830): 809-813. PubMed.</ref><ref name=Varghese>Varghese, B., Maher, J. E., Peterman, T. A., Branson, B. M. and Steketee, R. W. (2002). "Reducing the risk of sexual HIV transmission: quantifying the per-act risk for HIV on the basis of choice of partner, sex act, and condom use". Sex. Transm. Dis. 29 (1): 38-43. PubMed.</ref> | |||
| Percutaneous needle stick | 30<ref name=Bell>Bell, D. M. (1997). "Occupational risk of human immunodeficiency virus infection in healthcare workers: an overview.". Am. J. Med. 102 (5B): 9-15. PubMed.</ref> | |||
| Receptive penile-vaginal intercourse* | 10<ref name=ESG /><ref name=Varghese /><ref name=Leynaert>Leynaert, B., Downs, A. M. and de Vincenzi, I. (1998). "Heterosexual transmission of human immunodeficiency virus: variability of infectivity throughout the course of infection. European Study Group on Heterosexual Transmission of HIV". Am. J. Epidemiol. 148 (1): 88-96. PubMed.</ref> | |||
| Insertive anal intercourse* | 6.5<ref name=ESG /><ref name=Varghese /> | |||
| Insertive penile-vaginal intercourse* | 5<ref name=ESG /><ref name=Varghese /> | |||
| Receptive oral intercourse* | 1<ref name=Varghese />§ | |||
| Insertive oral intercourse* | 0.5<ref name=Varghese />§ | |||
| * assuming no condom use </br> § Source refers to oral intercourse performed on a man | ||||
The three main transmission routes of HIV are sexual contact, exposure to infected body fluids or tissues, and from mother to fetus or child during perinatal period. It is possible to find HIV in the saliva, tears, and urine of infected individuals, but due to the low concentration of virus in these biological liquids, the risk is negligible.
[edit] Sexual contact
The majority of HIV infections are acquired through unprotected sexual relations between partners, one of whom has HIV. Sexual transmission occurs with the contact between sexual secretions of one partner with the rectal, genital or oral mucous membranes of another. Unprotected receptive sexual acts are riskier than unprotected insertive sexual acts, with the risk for transmitting HIV from an infected partner to an uninfected partner through unprotected insertive anal intercourse greater than the risk for transmission through vaginal intercourse or oral sex. Oral sex is not without its risks as HIV is transmissible through both insertive and receptive oral sex.<ref name=Rothenberg>Rothenberg, R. B., Scarlett, M., del Rio, C., Reznik, D. and O'Daniels, C. (1998). "Oral transmission of HIV". AIDS 12 (16): 2095-2105. PubMed.</ref> The risk of HIV transmission from exposure to saliva is considerably smaller than the risk from exposure to semen; contrary to popular belief, one would have to swallow gallons of saliva from a carrier to run a significant risk of becoming infected.<ref name=Vincenzi>Mastro TD, de Vincenzi I (1996). "Probabilities of sexual HIV-1 transmission". AIDS 10 (Suppl A): S75-S82. PubMed.</ref>
Sexually transmitted infections (STI) increase the risk of HIV transmission and infection because they cause the disruption of the normal epithelial barrier by genital ulceration and/or microulceration; and by accumulation of pools of HIV-susceptible or HIV-infected cells (lymphocytes and macrophages) in semen and vaginal secretions. Epidemiological studies from sub-Saharan Africa, Europe and North America have suggested that there is approximately a four times greater risk of becoming infected with HIV in the presence of a genital ulcer such as those caused by syphilis and/or chancroid. There is also a significant though lesser increased risk in the presence of STIs such as gonorrhea, Chlamydial infection and trichomoniasis which cause local accumulations of lymphocytes and macrophages.<ref name=Laga>Laga, M., Nzila, N., Goeman, J. (1991). "The interrelationship of sexually transmitted diseases and HIV infection: implications for the control of both epidemics in Africa". AIDS 5 (Suppl 1): S55-S63. PubMed.</ref>
Transmission of HIV depends on the infectiousness of the index case and the susceptibility of the uninfected partner. Infectivity seems to vary during the course of illness and is not constant between individuals. An undetectable plasma viral load does not necessarily indicate a low viral load in the seminal liquid or genital secretions. Each 10-fold increment of blood plasma HIV RNA is associated with an 81% increased rate of HIV transmission.<ref name=Laga /><ref name=Tovanabutra>Tovanabutra, S., Robison, V., Wongtrakul, J., Sennum, S., Suriyanon, V., Kingkeow, D., Kawichai, S., Tanan, P., Duerr, A. and Nelson, K. E. (2002). "Male viral load and heterosexual transmission of HIV-1 subtype E in northern Thailand". J. Acquir. Immune. Defic. Syndr. 29 (3): 275-283. PubMed.</ref> Women are more susceptible to HIV-1 infection due to hormonal changes, vaginal microbial ecology and physiology, and a higher prevalence of sexually transmitted diseases.<ref name=Sagar>Sagar, M., Lavreys, L., Baeten, J. M., Richardson, B. A., Mandaliya, K., Ndinya-Achola, J. O., Kreiss, J. K., and Overbaugh, J. (2004). "Identification of modifiable factors that affect the genetic diversity of the transmitted HIV-1 population". AIDS 18 (4): 615-619. PubMed.</ref><ref name=Lavreys>Lavreys, L., Baeten, J. M., Martin, H. L. Jr., Overbaugh, J., Mandaliya, K., Ndinya-Achola, J., and Kreiss, J. K. (2004). "Hormonal contraception and risk of HIV-1 acquisition: results of a 10-year prospective study". AIDS 18 (4): 695-697. PubMed.</ref> People who are infected with HIV can still be infected by other, more virulent strains.
During a sexual act, only male or female condoms can reduce the chances of infection with HIV and other STDs and the chances of becoming pregnant. The best evidence to date indicates that typical condom use reduces the risk of heterosexual HIV transmission by approximately 80% over the long-term, though the benefit is likely to be higher if condoms are used correctly on every occasion.<ref name=Cayley>Cayley, W. E. Jr. (2004). "Effectiveness of condoms in reducing heterosexual transmission of HIV". Am. Fam. Physician 70 (7): 1268-1269. PubMed.</ref> The effective use of condoms and screening of blood transfusion in North America, Western and Central Europe is credited with contributing to the low rates of AIDS in these regions.
Promoting condom use, however, has often proved controversial and difficult. Many religious groups, most noticeably the Catholic Church, have opposed the use of condoms on religious grounds, and have sometimes seen condom promotion as an affront to the promotion of marriage, monogamy and sexual morality. This attitude is found among some health care providers and policy makers in sub-Saharan African nations, where HIV and AIDS prevalence is extremely high.<ref name=HRW>Human Rights Watch (2005). “Restrictions on Condoms”, The Less They Know, the Better. New York NY: Human Rights Watch.</ref> They also believe that the distribution and promotion of condoms is tantamount to promoting sex amongst the youth and sending the wrong message to uninfected individuals. However, no evidence has been produced that promotion of condom use increases sexual promiscuity.[citation needed] Pope Benedict XVI commissioned a report on whether it might be acceptable for Catholics to use condoms to protect life inside a marriage when one partner is infected with HIV, or is sick with AIDS.<ref name=Fisher>
Fisher, I.. "Ideals Collide as Vatican Rethinks Condom Ban", The New York Times, 2006-05-02. Retrieved on 2006-05-08. </ref> Defenders of the Catholic Church's role in AIDS and general STD prevention state that, while they may be against the use of contraception, they are strong advocates of abstinence outside marriage.<ref name=catechism>Catholic Church (1997). “Offenses against chastity”, Catechism of the Catholic Church : Second Edition. Vatican: Amministrazione Del Patrimonio Della Sede Apostolica, 2353. Retrieved on 2006-06-14.</ref> Conversely, some religious groups have argued that preventing HIV infection is a moral task in itself and that condoms are therefore acceptable or even praiseworthy from a religious point of view.
The male latex condom, if used correctly without oil-based lubricants, is the single most effective available technology to reduce the sexual transmission of HIV and other sexually transmitted infections. Manufacturers recommend that oil-based lubricants such as petroleum jelly, butter, and lard not be used with latex condoms as they weaken the latex, making the condoms porous. If necessary, manufacturers recommend using water-based lubricants. Oil-based lubricants can however be used with polyurethane condoms.<ref name=Durex>Durex. Module 5/Guidelines for Educators (Microsoft Word). Retrieved on 2006-04-17.</ref> Latex degrades over time, making them porous, which is why condoms have expiration dates. In Europe and the United States, condoms have to conform to European (EC 600) or American (D3492) standards to be considered protective against HIV transmission.
The female condom is an alternative to the male condom and is made from polyurethane, which allows it to be used in the presence of oil-based lubricants. They are larger than male condoms and have a stiffened ring-shaped opening, and are designed to be inserted into the vagina. The female condom contains an inner ring, which keeps the condom in place inside the vagina – inserting the female condom requires squeezing this ring.
With consistent and correct use of condoms, there is a very low risk of HIV infection. Studies on couples where one partner is infected show that with consistent condom use, HIV infection rates for the uninfected partner are below 1% per year.<ref name=WHOCondoms>WHO (August, 2003). Condom Facts and Figures. Retrieved on 2006-01-17.</ref>
The United States government and health organizations both endorse the ABC Approach to lower the risk of acquiring AIDS during sex:
- Abstinence or delay of sexual activity, especially for youth,
- Being faithful, especially for those in committed relationships,
- Condom use, for those who engage in risky behavior.
This approach has been very successful in Uganda, where HIV prevalence has decreased from 15% to 5%. However, more has been done than just this. As Edward Green, a Harvard medical anthropologist, put it, "Uganda has pioneered approaches towards reducing stigma, bringing discussion of sexual behavior out into the open, involving HIV-infected people in public education, persuading individuals and couples to be tested and counseled, improving the status of women, involving religious organizations, enlisting traditional healers, and much more." Other programs and initiatives promote condom use more heavily. Condom use is an integral part of the CNN Approach. This is:
- Condom use, for those who engage in risky behavior,
- Needles, use clean ones,
- Negotiating skills; negotiating safer sex with a partner and empowering women to make smart choices.
Criticism of the ABC approach is widespread because a faithful partner of an unfaithful partner is at risk of contracting HIV.<ref name=EconomistABC>The Economist (2005). Too much morality, too little sense. Retrieved on 2006-03-28.</ref>
Current research is clarifying the relationship between male circumcision and HIV in differing social and cultural contexts.<ref name=Siegfred>
Siegfried, N., Muller, M., Deeks, J., Volmink, J., Egger, M., Low, N., Walker, S. and Williamson, P. (2005). "HIV and male circumcision--a systematic review with assessment of the quality of studies". Lancet Infect. Dis. 5 (3): 165-173. PubMed.</ref> UNAIDS believes that it is premature to recommend male circumcision services as part of HIV prevention programs<ref name=WHOcircumcision>WHO (2005). UNAIDS statement on South African trial findings regarding male circumcision and HIV. Retrieved on 2006-03-28.</ref> even though male circumcision may lead to a reduction of infection risk in heterosexual men by up to 60%.<ref name=Williams>Williams BG, Lloyd-Smith JO, Gouws E, Hankins C, Getz WM, Hargrove J, de Zoysa I, Dye C, Auvert B. (2006). "The Potential Impact of Male Circumcision on HIV in Sub-Saharan Africa.". PLoS Med 3 (7): e262. PubMed.</ref> Moreover, South African medical experts are concerned that the repeated use of unsterilized blades in the ritual circumcision of adolescent boys may be spreading HIV.<ref name=Kaisercircum>Various (2005). Repeated Use of Unsterilized Blades in Ritual Circumcision Might Contribute to HIV Spread in S. Africa, Doctors Say. Kaisernetwork.org. Retrieved on 2006-03-28.</ref>
[edit] Exposure to infected body fluids
This transmission route is particularly relevant to intravenous drug users, hemophiliacs and recipients of blood transfusions and blood products. Sharing and reusing syringes contaminated with HIV-infected blood represents a major risk for infection with not only HIV, but also hepatitis B and hepatitis C. Needle sharing is the cause of one third of all new HIV-infections and 50% of hepatitis C infections in Northern America, China, and Eastern Europe. The risk of being infected with HIV from a single prick with a needle that has been used on an HIV infected person is thought to be about 1 in 150 (see table above). Post-exposure prophylaxis with anti-HIV drugs can further reduce that small risk.<ref name=Fan>Fan, H. (2005). Fan, H., Conner, R. F. and Villarreal, L. P. eds: AIDS: science and society, 4th, Boston, MA: Jones and Bartlett Publishers. ISBN 0-7637-0086-X.</ref> Health care workers (nurses, laboratory workers, doctors etc) are also concerned, although more rarely. This route can affect people who give and receive tattoos and piercings. Universal precautions are frequently not followed in both sub-Saharan Africa and much of Asia because of both a shortage of supplies and inadequate training. The WHO estimates that approximately 2.5% of all HIV infections in sub-Saharan Africa are transmitted through unsafe healthcare injections.<ref name=WHOJapan>WHO (2003-03-17). WHO, UNAIDS Reaffirm HIV as a Sexually Transmitted Disease. Retrieved on 2006-01-17.</ref> Because of this, the United Nations General Assembly, supported by universal medical opinion on the matter, has urged the nations of the world to implement universal precautions to prevent HIV transmission in health care settings.<ref name=PHR>Physicians for Human Rights (2003-03-13). HIV Transmission in the Medical Setting: A White Paper by Physicians for Human Rights. Partners in Health. Retrieved on 2006-03-01.</ref><ref name=UNGA>United Nations General Assembly (2001). Declaration of Commitment on HIV/AIDS Global Crisis — Global Action. Retrieved on 2006-03-01.</ref>
The risk of transmitting HIV to blood transfusion recipients is extremely low in developed countries where improved donor selection and HIV screening is performed. However, according to the WHO, the overwhelming majority of the world's population does not have access to safe blood and "between 5% and 10% of HIV infections worldwide are transmitted through the transfusion of infected blood and blood products".<ref name=WHO070401>WHO (2001). Blood safety....for too few. Retrieved on 2006-01-17.</ref>
Medical workers who follow universal precautions or body substance isolation such as wearing latex gloves when giving injections and washing the hands frequently can help prevent infection of HIV.
All AIDS-prevention organizations advise drug-users not to share needles and other material required to prepare and take drugs (including syringes, cotton balls, the spoons, water for diluting the drug, straws, crack pipes, etc). It is important that people use new or properly sterilized needles for each injection. Information on cleaning needles using bleach is available from health care and addiction professionals and from needle exchanges. In some developed countries, clean needles are available free in some cities, at needle exchanges or safe injection sites. Additionally, many nations have decriminalized needle possession and made it possible to buy injection equipment from pharmacists without a prescription.
[edit] Mother-to-child transmission (MTCT)
The transmission of the virus from the mother to the child can occur in utero during the last weeks of pregnancy and at childbirth. In the absence of treatment, the transmission rate between the mother to the child during pregnancy, labor and delivery is 25%. However, when the mother has access to antiretroviral therapy and gives birth by caesarean section, the rate of transmission is just 1%.<ref name=Coovadia /> A number of factors influence the risk of infection, particularly the viral load of the mother at birth (the higher the load, the higher the risk). Breastfeeding increases the risk of transmission by 10–15%. This risk depends on clinical factors and may vary according to the pattern and duration of breast-feeding.
Studies have shown that antiretroviral drugs, caesarean delivery and formula feeding reduce the chance of transmission of HIV from mother to child.<ref name=Sperling>Sperling, R. S., Shapirom D. E., Coombsm R. W., Todd, J. A., Herman, S. A., McSherry, G. D., O'Sullivan, M. J., Van Dyke, R. B., Jimenez, E., Rouzioux, C., Flynn, P. M. and Sullivan, J. L. (1996). "Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant". N. Engl. J. Med. 335 (22): 1621-1629. PubMed.</ref> Current recommendations state that when replacement feeding is acceptable, feasible, affordable, sustainable and safe, HIV-infected mothers should avoid breast-feeding their infant. However, if this is not the case, exclusive breast-feeding is recommended during the first months of life and discontinued as soon as possible.<ref name=UNAIDS2006>UNAIDS (2005). AIDS epidemic update, 2005 (PDF). Retrieved on 2006-01-17.</ref> In 2005, around 700,000 children under 15 contracted HIV, mainly through MTCT, with 630,000 of these infections occurring in Africa.<ref name=avert> Berry, S. (2006-06-08). Children, HIV and AIDS. avert.org. Retrieved on 2006-06-15.</ref> Of the estimated 2.3 million [1.7-3.5 million] children currently living with HIV, 2 million (almost 90%) live in sub-Saharan Africa.<ref name=UNAIDS2006 />
Prevention strategies are well known in developed countries, however, recent epidemiological and behavioral studies in Europe and North America have suggested that a substantial minority of young people continue to engage in high-risk practices and that despite HIV/AIDS knowledge, young people underestimate their own risk of becoming infected with HIV. <ref name=Dias>Dias, S. F., Matos, M. G. and Goncalves, A. C. (2005). "Preventing HIV transmission in adolescents: an analysis of the Portuguese data from the Health Behaviour School-aged Children study and focus groups". Eur. J. Public Health 15 (3): 300-304. PubMed.</ref> However, transmission of HIV between intravenous drug users has clearly decreased, and HIV transmission by blood transfusion has become quite rare in developed countries.
[edit] Treatment
There is currently no vaccine or cure for HIV or AIDS. The only known methods of prevention are based on avoiding exposure to the virus or, failing that, an antiretroviral treatment directly after a highly significant exposure, called post-exposure prophylaxis (PEP).<ref name=Fan> (2005) Fan, H., Conner, R. F. and Villarreal, L. P. eds: AIDS : science and society, 4th edition, Boston, MA: Jones and Bartlett Publishers. ISBN 0-7637-0086-X.</ref> PEP has a very demanding four week schedule of dosage. It also has very unpleasant side effects including diarrhea, malaise, nausea and fatigue.<ref name=PEPpocketguide>Department of Health and Human Services (February, 2006). A Pocket Guide to Adult HIV/AIDS Treatment February 2006 edition. Retrieved on 2006-09-01.</ref>
Current treatment for HIV infection consists of highly active antiretroviral therapy, or HAART.<ref name=DhhsHivTreatment>Department of Health and Human Services (February, 2006). A Pocket Guide to Adult HIV/AIDS Treatment February 2006 edition. Retrieved on 2006-09-01.</ref> This has been highly beneficial to many HIV-infected individuals since its introduction in 1996 when the protease inhibitor-based HAART initially became available.<ref name=Pallelal>Palella, F. J., Delaney, K. M., Moorman, A. C., Loveless, M. O., Fuhrer, J., Satten, G. A., Aschman, D. J. and Holmberg, S. D. (1998). "Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection". N. Engl. J. Med. 338 (13): 853-860. PubMed.</ref> Current optimal HAART options consist of combinations (or "cocktails") consisting of at least three drugs belonging to at least two types, or "classes," of anti-retroviral agents. Typical regimens consist of two nucleoside analogue reverse transcriptase inhibitors (NARTIs or NRTIs) plus either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI). Because HIV disease progression in children is more rapid than in adults, and laboratory parameters are less predictive of risk for disease progression, particularly for young infants, treatment recommendations are more aggressive for children than for adults.<ref name=2005dhhsHivChildren>Department of Health and Human Services Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children (November 3, 2005). Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection (PDF). Retrieved on 2006-01-17.</ref> In developed countries where HAART is available, doctors assess the viral load, rapidity in CD4 decline, and patient readiness while deciding when to recommend initiating treatment.<ref name=2005DhhsHivTreatment>Department of Health and Human Services Panel on Clinical Practices for Treatment of HIV Infection (October 6, 2005). Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents (PDF). Retrieved on 2006-01-17.</ref>
HAART allows the stabilisation of the patient’s symptoms and viremia, but it neither cures the patient of HIV, nor alleviates the symptoms, and high levels of HIV-1, often HAART resistant, return once treatment is stopped.<ref name=martinez>Martinez-Picado, J., DePasquale, M. P., Kartsonis, N., Hanna, G. J., Wong, J., Finzi, D., Rosenberg, E., Gunthard, H. F., Sutton, L., Savara, A., Petropoulos, C. J., Hellmann, N., Walker, B. D., Richman, D. D., Siliciano, R. and D'Aquila, R. T. (2000). "Antiretroviral resistance during successful therapy of human immunodeficiency virus type 1 infection". Proc. Natl. Acad. Sci. U. S. A. 97 (20): 10948-10953. PubMed.</ref><ref name=Dybul>Dybul, M., Fauci, A. S., Bartlett, J. G., Kaplan, J. E., Pau, A. K.; Panel on Clinical Practices for Treatment of HIV. (2002). "Guidelines for using antiretroviral agents among HIV-infected adults and adolescents". Ann. Intern. Med. 137 (5 Pt 2): 381-433. PubMed.</ref> Moreover, it would take more than the lifetime of an individual to be cleared of HIV infection using HAART.<ref name=blankson>Blankson, J. N., Persaud, D., Siliciano, R. F. (2002). "The challenge of viral reservoirs in HIV-1 infection". Annu. Rev. Med. 53: 557-593. PubMed.</ref> Despite this, many HIV-infected individuals have experienced remarkable improvements in their general health and quality of life, which has led to the plummeting of HIV-associated morbidity and mortality.<ref name=Pallelal>Palella, F. J., Delaney, K. M., Moorman, A. C., Loveless, M. O., Fuhrer, J., Satten, G. A., Aschman, D. J. and Holmberg, S. D. (1998). "Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection". N. Engl. J. Med. 338 (13): 853-860. PubMed.</ref><ref name=Wood>Wood, E., Hogg, R. S., Yip, B., Harrigan, P. R., O'Shaughnessy, M. V. and Montaner, J. S. (2003). "Is there a baseline CD4 cell count that precludes a survival response to modern antiretroviral therapy?". AIDS 17 (5): 711-720. PubMed.</ref><ref name=Chene>Chene, G., Sterne, J. A., May, M., Costagliola, D., Ledergerber, B., Phillips, A. N., Dabis, F., Lundgren, J., D'Arminio Monforte, A., de Wolf, F., Hogg, R., Reiss, P., Justice, A., Leport, C., Staszewski, S., Gill, J., Fatkenheuer, G., Egger, M. E. and the Antiretroviral Therapy Cohort Collaboration. (2003). "Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies". Lancet 362 (9385): 679-686. PubMed.</ref> In the absence of HAART, progression from HIV infection to AIDS occurs at a median of between nine to ten years and the median survival time after developing AIDS is only 9.2 months.<ref name=Morgan2 /> Still, for some patients - and in many clinical cohorts this may be more than fifty percent of patients - HAART achieves far less than optimal results. This is due to a variety of reasons such as medication intolerance/side effects, prior ineffective antiretroviral therapy and infection with a drug-resistant strain of HIV. However, non-adherence and non-persistence with antiretroviral therapy is the major reason most individuals fail to get any benefit from and develop resistance to HAART.<ref name=becker>Becker SL, Dezii CM, Burtcel B, Kawabata H, Hodder S. (2002). "Young HIV-infected adults are at greater risk for medication nonadherence". MedGenMed. 4 (3): 21. PubMed.</ref> The reasons for non-adherence and non-persistence with HAART are varied and overlapping. Major psychosocial issues, such as poor access to medical care, inadequate social supports, psychiatric disease and drug abuse contribute to non-adherence. The complexity of these HAART regimens, whether due to pill number, dosing frequency, meal restrictions or other issues along with side effects that create intentional non-adherence also has a weighty impact.<ref name=Nieuwkerk>Nieuwkerk, P., Sprangers, M., Burger, D., Hoetelmans, R. M., Hugen, P. W., Danner, S. A., van Der Ende, M. E., Schneider, M. M., Schrey, G., Meenhorst, P. L., Sprenger, H. G., Kauffmann, R. H., Jambroes, M., Chesney, M. A., de Wolf, F., Lange, J. M. and the ATHENA Project. (2001). "Limited Patient Adherence to Highly Active Antiretroviral Therapy for HIV-1 Infection in an Observational Cohort Study". Arch. Intern. Med. 161 (16): 1962-1968. PubMed.</ref><ref name=Kleeberger>Kleeberger, C., Phair, J., Strathdee, S., Detels, R., Kingsley, L. and Jacobson, L. P. (2001). "Determinants of Heterogeneous Adherence to HIV-Antiretroviral Therapies in the Multicenter AIDS Cohort Study". J. Acquir. Immune Defic. Syndr. 26 (1): 82-92. PubMed.</ref><ref name=heath>Heath, K. V., Singer, J., O'Shaughnessy, M. V., Montaner, J. S. and Hogg, R. S. (2002). "Intentional Nonadherence Due to Adverse Symptoms Associated With Antiretroviral Therapy". J. Acquir. Immune Defic. Syndr. 31 (2): 211-217.