HIV AIDS medical therapy
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HIV AIDS medical therapy On the Web |
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Risk calculators and risk factors for HIV AIDS medical therapy |
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:
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs).
- Nucleoside reverse transcriptase inhibitors (NRTIs).
- Protease inhibitors (PIs).
- Fusion inhibitors.
- 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. [1]
Anti Retroviral Drug Classes
| Drug Name | Dose | Adverse Events |
|---|---|---|
| Nucleoside Reverse Transcriptase Inhibitors (NRTIs) | ||
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300 mg BID or 600 mg once daily | Fever, rash, nausea, vomiting, diarrhea, abdominal pain, malaise, fatigue, sore throat, cough, shortness of breath. |
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400 mg once daily In combination with TDF: 200 mg once daily |
Pancreatitis, nausea, vomiting, peripheral neuropathy, retinal changes, optic neuritis, lactic acidosis with hepatic steatosis. |
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200 mg once daily | Hyperpigmentation, skin discoloration |
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250-300 mg BID | Macrocytic anemia, neutropenia, nausea, vomiting, headache, insomnia, asthenia, nail pigmentation, lactic acidosis, severe hepatomegaly with hepatic steatosis (rare), hyperlipidemia, insulin resistance/diabetes mellitus, lipoatrophy, myopathy. |
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150 mg BID or 300 mg once daily | Minimal toxicity, severe acute exacerbation of hepatitis may occur in HBV coinfected patients who discontinue 3TC. |
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>60 kg: 40 mg BID <60 kg: 250 mg BID |
Peripheral neuropathy, lipoatrophy, pancreatitis, lactic acidosis, severe hepatomegaly with hepatic steatosis (rare), hyperlipidemia, insulin resistance/diabetes mellitus, rapidly progressive ascending neuromuscular weakness (rare). |
| 300 mg once daily | Renal insufficiency, Fanconi syndrome, osteomalacia, decrease in bone mineral density, severe acute exacerbation of
hepatitis may occur in HBV coinfected patients who discontinue TDF, asthenia, headache, diarrhea, nausea, vomiting, and flatulence. | |
| Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) | ||
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600 mg once daily | Rash, increased transaminase levels, hyperlipidemia, dizziness, somnolence, insomnia, depression, suicidality, confusion, abnormal thinking, impaired concentration, amnesia, agitation, depersonalization, hallucinations, and euphoria |
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200 mg BID | Rash, Stevens-Johnson syndrome, nausea |
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200 mg once daily for 14 days, then 200 mg BID or 400 mg once daily | Rash, Stevens-Johnson syndrome, nausea, hepatitis |
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25 mg once daily | Rash, depression, insomnia, headache, hepatotoxicity |
| Protease Inhibitors (PIs) | ||
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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 |
Indirect hyperbilirubinemia, PR interval prolongation, hyperglycemia, fat maldistribution, cholelithiasis, nephrolithiasis, renal insufficiency, increase in transaminase levels, hyperlipidemia, skin rash |
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800 mg once daily | Skin rash, Stevens-Johnson syndrome, hepatotoxicity, diarrhea, nausea, headache, hyperlipidemia, fat maldistribution, hyperglycemia. |
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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 |
Skin rash, diarrhea, nausea, vomiting, headache, hyperlipidemia, hyperglycemia, increase in transaminase levels, nephrolithiasis, fat maldistribution. |
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800 mg q8h | Nephrolithiasis, nausea, hepatitis, indirect hyperbilirubinemia, hyperlipidemia, headache, asthenia, blurred vision, dizziness, rash, metallic taste, thrombocytopenia, alopecia, hemolytic anemia, hyperglycemia, fat maldistribution. |
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400 mg/100 mg BID or 800 mg/200 mg once daily | Diarrhea, nausea, vomiting, pancreatitis, asthenia, hyperlipidemia, hyperglycemia, fat maldistribution, increase in transaminase levels, PR interval prolongation, insulin resistance/diabetes mellitus. |
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1250 md BID or 750 mg TID | Diarrhea, hyperlipidemia, hyperglycemia, fat maldistribution, increase in transaminase levels. |
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100-400 mg/d q12-24h | Diarrhea, nausea, vomiting, paresthesia, hyperlipidemia, hepatitis, asthenia, taste perversion, hyperglycemia, fat maldistribution. |
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1000 mg BID | Diarrhea, nausea, vomiting, headache, hyperlipidemia, hyperglycemia, fat maldistribution, PR interval prolongation, insulin resistance/diabetes mellitus. |
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500 mg BID | Hepatotoxicity, skin rash, hyperlipidemia, hyperglycemia, fat maldistribution. |
| Integrase Inhibitors | ||
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50 mg q12-24h | Rash, insomnia, headache. |
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150 mg once daily | Nausea, diarrhea, decrease bone density, severe acute exacerbation of hepatitis may occur in HBV coinfected patients. |
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400 mg BID | Rash, Steven-Johnson syndrome, toxic epidermal necrolysis, nausea, headache, diarrhea, pyrexia, CPK elevation. |
| Fusion Inhibitor | ||
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90 mg SQ BID | Local injection reactions, increased incidence of bacterial pneumonia, rash, fever, nausea. |
| CCR5 Antagonist | ||
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150-600 mg BID | Abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, upper respiratory tract infections, hepatotoxicity. |
| Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [2] | ||
Goals of 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:
- Two nucleoside analogue reverse transcriptase inhibitors (NARTIs or NRTIs) PLUS
- Either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI).
- 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:
- 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 inhibitors (eg, enfuvirtide) are not approved for treatment-naive 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.
Anti Retroviral Regimens
▸ Click on the following categories to expand treatment regimens.
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Recommended Regimens ▸ NNRTI-Based Regimen ▸ PI-Based Regimen ▸ INSTI-Based Regimen Alternative Regimens ▸ PI-Based Regimen ▸ INSTI-Based Regimen
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Monitoring CD4 and Viral Load
| Scenario | CD4 Monitoring | Viral Load Monitoring |
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| 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] | ||
Other Laboratory Monitoring
| Time-point | Laboratory Tests | ||
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| At HIV diagnosis |
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| At initiation of ART |
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| After 2-8 weeks after ART initiation |
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| Every 3-6 months |
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| Every 6-12 months |
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| Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [2] | |||
References
- ↑ 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.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014".
- ↑ 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) - ↑ 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)