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


===Anti Retroviral Drug Classes===
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===Guidelines for Initiation of ART===
===Initiation of ART===
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Skipping medications makes it easier for drug resistance to develop. HIV can develop resistance to the anti-HIV medications in a person’s current regimen or to other, similar anti-HIV medications not yet taken, limiting options for successful HIV treatment. And drug-resistant strains of HIV can be transmitted to others, too. Although there are many different anti-HIV medications and treatment regimens, studies show that a person’s first regimen offers the best chance for long-term treatment success. Adhering to the regimen from the start will help ensure that the HIV treatment is successful.
Skipping medications makes it easier for drug resistance to develop. HIV can develop resistance to the anti-HIV medications in a person’s current regimen or to other, similar anti-HIV medications not yet taken, limiting options for successful HIV treatment. And drug-resistant strains of HIV can be transmitted to others, too. Although there are many different anti-HIV medications and treatment regimens, studies show that a person’s first regimen offers the best chance for long-term treatment success. Adhering to the regimen from the start will help ensure that the HIV treatment is successful.
==Patient Monitoring during ART==
A patient monitoring system is the backbone of clinical care, treatment and prevention by the clinical team caring for groups of patients.


===Visit Frequency===
===Visit Frequency===
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Transient increase in the viral load can be present in acute illness and [[vaccination]]s.




Transient increase in the viral load can be present in acute illness and [[vaccination]]s.
===Virologic Failure===
===Virologic Failure===
It is defined either as primary failure to achieve a viral load <50 copies/mL or any sustained recurrence of viremia to >50 copies/mL after initial viral suppression.<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=2012-02-20}}</ref>
It is defined either as primary failure to achieve a viral load <50 copies/mL or any sustained recurrence of viremia to >50 copies/mL after initial viral suppression.<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=2012-02-20}}</ref>
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}}</ref>
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==NIH Recommendations==
==NIH Recommendations==
===NIH Recommendations:Treatment-Naive Patients===
===NIH Recommendations:Treatment-Naive Patients===

Revision as of 20:56, 1 October 2014

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

Overview

The primary goal of antiretroviral therapy (ART) is to reduce HIV-associated morbidity and mortality. This goal is best accomplished by using effective ART to maximally inhibit HIV replication, as defined by achieving and maintaining plasma HIV RNA (viral load) below levels detectable by commercially available assays. Durable viral suppression improves immune function and quality of life, lowers the risk of both AIDS-defining and non-AIDS-defining complications, and prolongs life. Based on emerging evidence, additional benefits of ART include a reduction in HIV-associated inflammation and possibly its associated complications.

Medical Therapy

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

  1. Non-nucleoside reverse transcriptase inhibitors (NNRTIs).
  2. Nucleoside reverse transcriptase inhibitors (NRTIs).
  3. Protease inhibitors (PIs).
  4. Fusion inhibitors.
  5. CCR5 antagonists.
  6. Integrase inhibitors.

Multidrug regimen has proved to be very beneficial because of reduction in progression to AIDS, opportunistic infections, rate of hospitalizations and deaths. [1]

Anti Retroviral Drug Classes
Drug Name Dose
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
300 mg BID or 600 mg once daily
400 mg once daily
In combination with TDF: 200 mg once daily
200 mg once daily
250-300 mg BID
150 mg BID or 300 mg once daily
>60 kg: 40 mg BID
<60 kg: 250 mg BID
300 mg once daily
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
600 mg once daily
200 mg BID
200 mg once daily for 14 days, then 200 mg BID or 400 mg once daily
25 mg once daily
Protease Inhibitors (PIs)
400 mg once daily
In combination with TDF: 300 mg + RTV 100 mg once daily
In combination with EFV: 400 mg + RTV 100 mg once daily
800 mg/d
1400 mg BID or
700 mg + RTV 100 mg BID
In combination with EFV: 700 mg + RTV 100 mg BID or 1400 mg + RTV 300 mg once daily
800 mg q8h
400 mg/100 mg BID or 800 mg/200 mg once daily
1250 md BID or 750 mg TID
100-400 mg/d q12-24h
1000 mg BID
500 mg BID
Integrase Inhibitors
50 mg q12-24h
150 mg once daily
400 mg BID
Fusion Inhibitor
90 mg SQ BID
CCR5 Antagonist
150-600 mg BID
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [2]

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)

  • Current optimal HAART options consist of drug combinations consisting of at least three drugs belonging to at least two classes of antiretroviral agents.
  • Typical regimens consist of:
  • 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.[3][4]
  • Antiretroviral therapy should be initiated in the following patient populations:
  • 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.

Anti Retroviral Regimens

▸ Click on the following categories to expand treatment regimens.

Recommended Regimens

  ▸  NNRTI-Based Regimen

  ▸  PI-Based Regimen

  ▸  INSTI-Based Regimen

Alternative Regimens

  ▸  PI-Based Regimen

  ▸  INSTI-Based Regimen


Recommended Regimen
NNRTI-Based Regimen
▸ Efavirenz/Tenofovir/Emtricitabine†
NNRTI-based regimen for patients with HIV RNA < 100,000 copies/mL
▸ Efavirenz
PLUS
▸ Abacavir/Lamivudine† (only for HLA-B*5701 negative patients)
OR
▸ Rilpivirine/Tenofovir/Emtricitabine† (only for patients with CD4 < 200 cells/mm³)
†Emtricitabine may be substituted for lamivudine or vice versa
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [2]
Recommended Regimen
PI-Based Regimen
▸ Atazanavir/Ritonavir(low dose)
PLUS
▸ Tenofovir/Emtricitabine†
OR
▸ Darunavir/Ritonavir(low dose)
PLUS
▸ Tenofovir/Emtricitabine†
PI-based regimen for patients with HIV RNA < 100,000 copies/mL
OR
▸ Atazanavir/Ritonavir(low dose)
PLUS
▸ Abacavir/Lamivudine† (only for HLA-B*5701 negative patients)
†Emtricitabine may be substituted for lamivudine or vice versa
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [2]
Recommended Regimen
INSTI-Based Regimen
▸ Dolutegravir
PLUS
▸ Abacavir/Lamivudine† (only for HLA-B*5701 negative patients)
OR
▸ Dolutegravir
PLUS
▸ Tenofovir/Emtricitabine†
OR
▸ Elvitegravir/Cobicistat/Tenofovir/Emtricitabine†(contraindicated in patients with CrCl <70mL/min)
OR
▸ Raltegravir
PLUS
▸ Tenofovir/Emtricitabine†
†Emtricitabine may be substituted for lamivudine or vice versa
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.[2]
Alternative Regimen
PI-Based Regimens
▸ Darunavir/Ritonavir(low dose)
PLUS
▸ Abacavir/Lamivudine† (only for HLA-B*5701 negative patients)
OR
▸ Lopinavir/Ritonavir(low dose)
PLUS
▸ Abacavir/Lamivudine† (only for HLA-B*5701 negative patients)
OR
▸ Lopinavir/Ritonavir(low dose)
PLUS
▸Tenofovir/Emtricitabine†
†Emtricitabine may be substituted for lamivudine or vice versa
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [2]
Alternative Regimen
INSTI-Based Regimens
▸ Raltegravir
PLUS
▸ Abacavir/Lamivudine† (only for HLA-B*5701 negative patients)
†Emtricitabine may be substituted for lamivudine or vice versa
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [2]


Monitoring CD4 and Viral Load
Scenario CD4 Monitoring Viral Load Monitoring
Before receiving ART Yes Yes
While receiving ART 3 month after initiation of ART 2-4 weeks after initiation of ART, then every 4-8 weeks
ART regimen is modified due to drug toxicity Will depend on previous CD4 counts 4-8 weeks after modification of regimen
ART regimen is modified due to virologic failure Every 3-6 months 2-4 weeks after initiation of ART, then every 4-8 weeks
During the first 2 years of ART Every 3-6 months Every 3-4 months
While on ART with detectable viremia (>200 copies/mL) Every 3-6 months Every 3 months
Change in clinical status
(new HIV clinical symptom or initiation of interferon, chronic systemic corticosteroids, or antineoplastic therapy) 		Will depend on the clinical scenario Every 3 months
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [2]

References

  1. ↑ Sterne JA, Hernán MA, Ledergerber B, Tilling K, Weber R, Sendi P, Rickenbach M, Robins JM, Egger M (2005). "Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study". Lancet. 366 (9483): 378–84. doi:10.1016/S0140-6736(05)67022-5. PMID 16054937. Retrieved 2012-02-15.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014".
  3. ↑ 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 (2003). "Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection". N. Engl. J. Med. 349 (24): 2304–15. doi:10.1056/NEJMoa030265. PMID 14668456. Retrieved 2012-02-16. Unknown parameter |month= ignored (help)
  4. ↑ Puls RL, Srasuebkul P, Petoumenos K, Boesecke C, Duncombe C, Belloso WH, Molina JM, Li L, Avihingsanon A, Gazzard B, Cooper DA, Emery S (2010). "Efavirenz versus boosted atazanavir or zidovudine and abacavir in antiretroviral treatment-naive, HIV-infected subjects: week 48 data from the Altair study". Clin. Infect. Dis. 51 (7): 855–64. doi:10.1086/656363. PMID 20735258. Retrieved 2012-02-16. Unknown parameter |month= ignored (help)
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