View source for HIV AIDS medical therapy

[[Image:Abacavir (Ziagen) 300mg.jpg|right|thumb|100px|''[[Abacavir]]'' – a nucleoside analog reverse transcriptase inhibitors (NARTIs or NRTIs)]]
[[Image:Abacavir_structure.svg|thumb|The chemical structure of Abacavir]]

{{AIDS}}

'''For AIDS Patient Information click [[AIDS Patient Information|here]]'''

{{CMG}}

==Overview==
'''Acquired immune deficiency syndrome (AIDS''') is a [[syndrome|collection of symptoms and infections]] resulting from the specific damage to the [[immune system]] caused by the [[HIV|human immunodeficiency virus]] (HIV) in humans,<ref>{{cite web
|url=http://www.niaid.nih.gov/Publications/hivaids/hivaids.htm
|title=The Relationship Between the Human Immunodeficiency Virus and the Acquired Immunodeficiency Syndrome |publisher= NIAID
|accessdate=2008-03-10}}</ref> and similar viruses in other species ([[Simian immunodeficiency virus|SIV]], [[Feline immunodeficiency virus|FIV]], etc.)

Anti-HIV medications (also called antiretrovirals) are grouped into six drug classes according to their mechanism of action. 
The six classes are as follows:

# [[Non-nucleoside reverse transcriptase inhibitors]] (NNRTIs).
# [[Nucleoside reverse transcriptase inhibitors]] (NRTIs).
# [[Protease inhibitors]] (PIs).
# [[Fusion inhibitor]]s.
# [[CCR5]] antagonists.
# [[Integrase inhibitors]].

Multidrug regimen has proved to be very beneficial because of reduction in progression to AIDS, opportunistic infections, rate of hospitalizations and deaths. <ref name="pmid16054937">{{cite journal |author=Sterne JA, Hernán MA, Ledergerber B, Tilling K, Weber R, Sendi P, Rickenbach M, Robins JM, Egger M |title=Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study |journal=Lancet |volume=366 |issue=9483 |pages=378–84 |year=2005 |pmid=16054937 |doi=10.1016/S0140-6736(05)67022-5 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(05)67022-5 |accessdate=2012-02-15}}</ref>

==Goals of therapy==
DHHS ART Guidelines present the following goals for therapy: 
* Durable suppression of HIV viral load ( to <50 cells/mL ).
* Restoration of normal CD4 cell count.
* Prevention of transmission of the disease.
* Prevention of building of drug resistance.
* Improvement in quality of life of the patient.

Uncontrolled viremia causes inflammation and immune activation, which has an overall effect on cardiovascular, renal and hepatic systems. Controlling viremia also controls these effects.

==Anti Retroviral Therapy (ART)==
===Indications===
The DHHS guidelines currently recommend the follwing:

{|border="1" align="center" style="background:white"
|-
| bgcolor="white" |'''Symptoms'''
| bgcolor="white" |'''CD4 count'''
| bgcolor="white" |'''Treatment'''
|-
| Asymptomatic
| <500
| Treatment should be offered.
|-
| Asymptomatic
| >500
| Treatment is optional.
|-
| [[AIDS history and symptoms#History and Symptoms|Symptomatic]]
| Any value
| Treatment should be initiated.<ref name="pmid20639566">{{cite journal |author=Thompson MA, Aberg JA, Cahn P, Montaner JS, Rizzardini G, Telenti A, Gatell JM, Günthard HF, Hammer SM, Hirsch MS, Jacobsen DM, Reiss P, Richman DD, Volberding PA, Yeni P, Schooley RT |title=Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel |journal=JAMA |volume=304 |issue=3 |pages=321–33 |year=2010 |month=July |pmid=20639566 |doi=10.1001/jama.2010.1004 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=20639566 |accessdate=2012-02-15}}</ref>
|}

===Selection of the regimen===
US Department of Health and Human Services (DHHS) have published guidelines for initial ART based on data from randomized controlled trials. 

Typical regimens consist of:
* Two [[nucleoside analogue reverse transcriptase inhibitor]]s (NARTIs or NRTIs) '''PLUS'''
* Either a [[protease inhibitor (pharmacology)|protease inhibitor]] or a [[non-nucleoside reverse transcriptase inhibitor]] (NNRTI). 
Following regimens are recommended by DHHS:
* An [[NNRTI]], [[efavirenz]] plus 2 [[NRTI]]s '''OR'''

* A boosted PI: [[atazanavir]] (ATV/r) once daily or [[darunavir]] (DRV/r) once daily plus 2 NRTIs  '''OR''' 

* An integrase inhibitor, [[raltegravir]] (400 mg twice daily) with 2 NRTIs.

The recommended NRTI coformulation is TDF/FTC in all of the above combinations.
In treatment-naive patients, four drug regimen is not found to be more efficacious than three-drug regimens and is associated with more adverse events.<ref name="pmid14668456">{{cite journal |author=Shafer RW, Smeaton LM, Robbins GK, De Gruttola V, Snyder SW, D'Aquila RT, Johnson VA, Morse GD, Nokta MA, Martinez AI, Gripshover BM, Kaul P, Haubrich R, Swingle M, McCarty SD, Vella S, Hirsch MS, Merigan TC |title=Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection |journal=N. Engl. J. Med. |volume=349 |issue=24 |pages=2304–15 |year=2003 |month=December |pmid=14668456 |doi=10.1056/NEJMoa030265 |url=http://dx.doi.org/10.1056/NEJMoa030265 |accessdate=2012-02-16}}</ref><ref name="pmid20735258">{{cite journal |author=Puls RL, Srasuebkul P, Petoumenos K, Boesecke C, Duncombe C, Belloso WH, Molina JM, Li L, Avihingsanon A, Gazzard B, Cooper DA, Emery S |title=Efavirenz versus boosted atazanavir or zidovudine and abacavir in antiretroviral treatment-naive, HIV-infected subjects: week 48 data from the Altair study |journal=Clin. Infect. Dis. |volume=51 |issue=7 |pages=855–64 |year=2010 |month=October |pmid=20735258 |doi=10.1086/656363 |url=http://www.cid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=20735258 |accessdate=2012-02-16}}</ref>

===Treatment-naive patients===
The DHHS Guidelines recommend that therapy should be initiated in the following patient populations:

* Patients with history of an AIDS-defining illness or with a CD4 count of less than 350/µL.

* Pregnant women with HIV infection.

* Patients with HIV-associated nephropathy.

* Patients with HIV and hepatitis B virus (HBV) coinfection who require treatment for HBV infection.

[[Fusion inhibitor]]s (eg, [[enfuvirtide]]) are not approved for treatment-naive patients.

===Treatment-experienced patients===
Treatment failure is defined by the following factors:
* '''Virologic failure''': which is defined as suboptimal viral suppression or loss of suppression (>50 HIV-1 RNA copies/mL).

* '''Immunologic failure ''': which is defined as failure to achieve or maintain CD4 cell count recovery despite effective viral suppression.

* Development of new opportunistic infections or neoplasms despite apparent CD4 count recovery.

===Initial HIV therapy===

NNRTI, PI, or integrase inhibitor-based regimen in combination with dual NRTIs is considered as an initial HIV therapy. Currently, CCR5 inhibitors are not  recommended due to lack of sufficient published data.  The particular choice of agent depends on the following factors:
*Side effect profiles.
*Comorbidities in patient.
*Potential drug interactions.
*Allergy history.
*Pregnancy status.
*Patient convenience.

=== Highly Active Anti-Retroviral Therapy ===
Current treatment for HIV infection consists of [[highly active antiretroviral therapy]], or HAART.<ref name=DhhsHivTreatment>{{

 cite web
 | publisher=Department of Health and Human Services
 | date=February 2006
 | url=http://hab.hrsa.gov/tools/HIVpocketguide/PktGARTtables.htm
 | title=A Pocket Guide to Adult HIV/AIDS Treatment February 2006 edition
 | accessdate = 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. 
Current optimal HAART options consist of combinations (or "cocktails") consisting of at least three drugs belonging to at least two types, or "classes," of [[antiretroviral]] agents. 

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>{{

 cite web
 | publisher=Department of Health and Human Services Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children
 | date=2005-11-03
 | url=http://www.aidsinfo.nih.gov/ContentFiles/PediatricGuidelines_PDA.pdf
 | title=Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection
 | format= PDF
 | accessdate = 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>{{

 cite web
 | publisher=Department of Health and Human Services Panel on Clinical Practices for Treatment of HIV Infection
 | date=2005-10-06
 | url=http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
 | title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents
 | format= PDF
 | accessdate = 2006-01-17

}}</ref>

HAART allows the stabilization 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>{{

 cite journal
 | author=Martinez-Picado J, DePasquale MP, Kartsonis N, et al| title=Antiretroviral resistance during successful therapy of human immunodeficiency virus type 1 infection | journal=Proc. Natl. Acad. Sci. U. S. A. | year=2000 | pages=10948&ndash;10953 | volume=97 | issue=20 | pmid=11005867

}}</ref><ref name=Dybul>{{

 cite journal
 | author=Dybul M, Fauci AS, Bartlett JG, Kaplan JE, Pau AK; Panel on Clinical Practices for Treatment of HIV.
 | title=Guidelines for using antiretroviral agents among HIV-infected adults and adolescents
 | journal=Ann. Intern. Med. | year=2002 | pages=381&ndash;433 | volume=137 | issue=5 Pt 2
 | pmid=12617573

}}</ref> Moreover, it would take more than the lifetime of an individual to be cleared of HIV infection using HAART.<ref name=blankson>{{

 cite journal
 | author=Blankson JN, Persaud D, Siliciano RF | title=The challenge of viral reservoirs in HIV-1 infection | journal=Annu. Rev. Med. | year=2002 | pages=557&ndash;593 | volume=53 | issue= | pmid=11818490

}}</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>{{

 cite journal
 | author=Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD | title=Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection | journal=N. Engl. J. Med. | year=1998 | pages=853&ndash;860 | volume=338 | issue=13 | pmid=9516219

}}</ref><ref name=Wood>{{

 cite journal
 | author=Wood E, Hogg RS, Yip B, Harrigan PR, O'Shaughnessy MV, Montaner JS
 | title=Is there a baseline CD4 cell count that precludes a survival response to modern antiretroviral therapy?
 | journal=AIDS | year=2003 | pages=711&ndash;720 | volume=17 | issue=5
 | pmid=12646794

}}</ref><ref name=Chene>{{

 cite journal
 | author=Chene G, Sterne JA, May M, Costagliola D, Ledergerber B, Phillips AN, 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 ME and the Antiretroviral Therapy Cohort Collaboration
 | title=Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies
 | journal=Lancet | year=2003 | pages=679&ndash;686 | volume=362 | issue=9385
 | pmid=12957089 | doi=10.1016/S0140-6736(03)14229-8 

}}</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&nbsp;months. HAART is thought to increase survival time by between 4 and 12&nbsp;years.<ref name=JTKing>{{

 cite journal
 | author=King JT, Justice AC, Roberts MS, Chang CH, Fusco JS and the CHORUS Program Team
 | title=Long-Term HIV/AIDS Survival Estimation in the Highly Active Antiretroviral Therapy Era
 | journal=Medical Decision Making | year=2003 | pages=9&ndash;20 | volume=23 | issue=1
 | pmid=12583451

}}</ref><ref name=Tassie>{{

 cite journal
 | author=Tassie JM, Grabar S, Lancar R, Deloumeaux J, Bentata M, Costagliola D and the Clinical Epidemiology Group from the French Hospital Database on HIV
 | title=Time to AIDS from 1992 to 1999 in HIV-1-infected subjects with known date of infection
 | journal=Journal of acquired immune deficiency syndromes | year=2002 | pages=81&ndash;7 | volume=30 | issue=1
 | pmid=12048367

}}</ref> This average reflects the fact that for some patients &ndash; and in many clinical cohorts this may be more than fifty percent of patients &ndash; 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>{{

 cite journal
 | author=Becker SL, Dezii CM, Burtcel B, Kawabata H, Hodder S. | title=Young HIV-infected adults are at greater risk for medication nonadherence | journal=MedGenMed. | year=2002 | pages=21 | volume=4| issue=3 | pmid=12466764

}}</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>{{

 cite journal
 | author=Nieuwkerk P, Sprangers M, Burger D, Hoetelmans RM, Hugen PW, Danner SA, van Der Ende ME, Schneider MM, Schrey G, Meenhorst PL, Sprenger HG, Kauffmann RH, Jambroes M, Chesney MA, de Wolf F, Lange JM and the ATHENA Project | title=Limited Patient Adherence to Highly Active Antiretroviral Therapy for HIV-1 Infection in an Observational Cohort Study | journal=Arch. Intern. Med. | year=2001 | pages=1962&ndash;1968 | volume=161 | issue=16 | pmid=11525698

}}</ref><ref name=Kleeberger>{{

 cite journal
 | author=Kleeberger C, Phair J, Strathdee S, Detels R, Kingsley L, Jacobson LP | title=Determinants of Heterogeneous Adherence to HIV-Antiretroviral Therapies in the Multicenter AIDS Cohort Study| journal=J. Acquir. Immune Defic. Syndr. | year=2001 | pages=82&ndash;92 | volume=26 | issue=1 | pmid=11176272

}}</ref><ref name=heath>{{

 cite journal
 | author=Heath KV, Singer J, O'Shaughnessy MV, Montaner JS, Hogg RS | title=Intentional Nonadherence Due to Adverse Symptoms Associated With Antiretroviral Therapy | journal=J. Acquir. Immune Defic. Syndr. | year=2002 | pages=211&ndash;217 | volume=31 | issue=2 | pmid=12394800

}}</ref> The side effects include [[lipodystrophy]], [[dyslipidaemia]], [[insulin resistance]], an increase in [[cardiovascular]] risks and [[birth defect]]s.<ref name=Montessori>{{

 cite journal |
 author=Montessori V, Press N, Harris M, Akagi L, Montaner JS |
 title=Adverse effects of antiretroviral therapy for HIV infection. |
 journal=CMAJ | year=2004 | pages=229&ndash;238 | volume=170 | issue=2 | pmid=14734438

}}</ref><ref name=Saitoh>{{

 cite journal
 | author=Saitoh A, Hull AD, Franklin P, Spector SA
 | title=Myelomeningocele in an infant with intrauterine exposure to efavirenz
 | journal=J. Perinatol. | year=2005 | pages=555&ndash;556 | volume=25 | issue=8
 | pmid=16047034 | doi=10.1038/sj.jp.7211343

}}</ref>

Daily multivitamin and mineral supplements have been found to reduce HIV disease progression among men and women. This could become an important low-cost intervention provided during early HIV disease to prolong the time before antiretroviral therapy is required.<ref name=Fawzi>{{

 cite journal
 | author=Fawzi W, Msamanga G, Spiegelman D, Hunter DJ
 | title=Studies of vitamins and minerals and HIV transmission and disease progression
 | journal=J. Nutrition| year=2005 | pages=938&ndash;944 | volume=135 | issue=4
 | pmid=15795466
}}
</ref> Some individual nutrients have also been tried.<ref name=Hurwitz>([[Selenium]]:) {{

 cite journal
 | author=Hurwitz BE, Klaus JR, Llabre MM, Gonzalez A, Lawrence PJ, Maher KJ, Greeson JM, Baum MK, Shor-Posner G, Skyler JS, Schneiderman N
 | title=Suppression of human immunodeficiency virus type 1 viral load with selenium supplementation: a randomized controlled trial
 | journal=Arch Intern Med.| year=2007 | pages=148&ndash;155 | volume=167 | issue=2
 | pmid=17242315
}}</ref><ref name=Cathcart1>([[Vitamin C]]:) {{

 cite journal
 | author=Cathcart RR
 | title=Vitamin C in the Treatment of Acquired Immune Deficiency Syndrome
 | journal=Medical Hypotheses | year=1984 | volume=14 | issue=4 | pages=423-433
 | pmid=6238227 | doi=10.1016/0306-9877(84)90149-X
 | url=http://www.doctoryourself.com/aids_cathcart.html

}}</ref> Anti-retroviral drugs are expensive, and the majority of the world's infected individuals do not have access to medications and treatments for HIV and AIDS.<ref name=Ferrantelli>{{

 cite journal
 | author=Ferrantelli F, Cafaro A, Ensoli B | title=Nonstructural HIV proteins as targets for prophylactic or therapeutic vaccines | journal=Curr Opin Biotechnol. | year=2004 | pages=543&ndash;556 | volume=15 | issue=6
 | pmid=15560981

}}</ref> It has been postulated that only a vaccine can halt the pandemic because a vaccine would possibly cost less, thus being affordable for developing countries, and would not require daily treatments.<ref name=Ferrantelli/> However, after over 20&nbsp;years of research, HIV-1 remains a difficult target for a vaccine.<ref name=Ferrantelli/>

Research to improve current treatments includes decreasing side effects of current drugs, further simplifying drug regimens to improve adherence, and determining the best sequence of regimens to manage drug resistance. A number of studies have shown that measures to prevent opportunistic infections can be beneficial when treating patients with HIV infection or AIDS. [[Vaccination]] against [[hepatitis]] A and B is advised for patients who are not infected with these viruses and are at risk of becoming infected.<ref name=Laurence>{{

 cite journal
 | author=Laurence J
 | title=Hepatitis A and B virus immunization in HIV-infected persons
 | journal=AIDS Reader | year=2006 | pages=15&ndash;17 | volume=16 | issue=1
 | pmid=16433468

}}</ref> Patients with substantial immunosuppression are also advised to receive prophylactic therapy for [[Pneumocystis jiroveci pneumonia]] (PCP), and many patients may benefit from prophylactic therapy for [[toxoplasmosis]] and [[Cryptococcus]] [[meningitis]] as well.<ref name=PEPpocketguide>{{

 cite web
 | publisher=Department of Health and Human Services
 | date = 2007-02-02
 | url=http://www.guideline.gov/summary/summary.aspx?ss=14&doc_id=6223&string=infected+AND+patients
 | title=Treating opportunistic infections among HIV-infected adults and adolescents. Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America.
 | accessdate = 2007-02-05

}}</ref>

Various forms of [[alternative medicine]] have been used to treat symptoms or alter the course of the disease.<ref name=Saltmarsh>{{

 cite journal
 | author=Saltmarsh S
 | title=Voodoo or valid? Alternative therapies benefit those living with HIV
 | journal=Positively Aware | year=2005 | pages=46 | volume=3 | issue=16
 | pmid=16479668 | url=http://www.tpan.com/publications/pa/may_jun_05/voodoo.shtml

}}
</ref> In the first decade of the [[epidemic]] when no useful conventional treatment was available, a large number of people with AIDS experimented with alternative therapies. The definition of "alternative therapies" in AIDS has changed since that time. Then, the phrase often referred to community-driven treatments, untested by government or pharmaceutical company research, that some hoped would directly suppress the virus or stimulate immunity against it. Examples of alternative medicine that people hoped would improve their symptoms or their quality of life include massage, stress management, herbal and flower remedies such as boxwood,<ref name=Pharo>{{

 cite journal
 | author=Pharo A, et al
 | title=Evaluation of the safety and efficacy of SPV-30 (boxwood extract) in patients with HIV disease
 | journal=Int Conf AIDS | year=1996 | issue=Jul 7–12 | pages=11:19 | id=abstract no. Mo. B.180
 | url=http://www.aegis.org/conferences/iac/1996/MoB180.html

}}
</ref><ref name=Durant>{{

 cite journal
 | author=Durant J, et al
 | title=Efficacy and safety of Buxussempervirens L. preparations (SPV-30) in HIV infected asymptomatic patients: a multi-centre, randomized, double-blind, placebo-controlled trial.
 | journal=Phytomedicine | year = 1998 | issue=5 | pages=1–10

}}
</ref> and [[acupuncture]];<ref name=Saltmarsh /> when used with conventional treatment, many now refer to these as "complementary" approaches. Despite the widespread use of complementary and alternative medicine by people living with HIV/AIDS, the effectiveness of these therapies has not been established.<ref name=Mills>{{

cite journal
 | author=Mills E, Wu P, Ernst E
 | title=Complementary therapies for the treatment of HIV: in search of the evidence.
 | journal=Int. J. STD AIDS.| year=2005 | pages=395&ndash;403 | volume=16 | issue=6
 | pmid=15969772

}}</ref>

==See Also==
*[[HIV#Treatment|HIV Treatment]]
* [[Antiretroviral drug]].
==References==
{{reflist|3}}