Haart
Synonym(s)
DefinitionThis section has been translated automatically.
General definitionThis section has been translated automatically.
HAART is the acronym for Highly Active Anti-Retroviral Therapy.
Notice! Due to the complexity of the therapy, it should only be initiated, discontinued or changed in close consultation with a specialised centre.
- By targeting the right combination of active ingredients at the right time, the measured viral load (detection by PCR) of sometimes 1.5 million copies/ml of blood can be pushed below the detection limit (this should not be confused with a cure). The life expectancy of HAART-treated patients gradually adjusts to normal life expectancy. A normal life is thus (almost) possible, although individual more aggressive forms of the disease and an increasing resistance problem should not be negated. It must therefore be stressed that there is no alternative to infection control (safer sex) as yet.
- HAART consists of a combination of at least three antiretroviral drugs from at least two drug classes. Currently, several drug classes are available:
- Nucleosidal reverse transcriptase inhibitors ( nucleoside analogues, NRTI)
- Nucleotidal reverse transcriptase inhibitors (nucleotide analogues, NtRTI)
- Non-nucleosidal reverse transcriptase inhibitors (NNRTI)
- protease inhibitors (PI)
- Fusion inhibitors
- Entry inhibitors
- Coreceptor antagonists
- Integrase inhibitors.
IndicationThis section has been translated automatically.
Undesirable effectsThis section has been translated automatically.
- Frequently, dermatological side effects are seen under HAART, especially drug exanthema, lipodystrophy syndromes. Clinically significant is the immune reconstruction syndrome with the unmasking of latent infectious diseases or the new occurrence or reactivation of pre-existing diseases.
- Antiretroviral therapy must be switched in up to 25% of all patients within the first year due to side effects.
- Drug exanthema: Drug exanthema is triggered primarily by NNRTIs. In cases of mild, non-bullous reactions without general symptoms or mucosal involvement, HAART can be continued. The differential diagnostic differentiation from, for example, viral exanthema and syphilis can be difficult.
- Hypersensitivity syndrome: The presence of a possibly life-threatening hypersensitivity reaction (HSR), which is sometimes also referred to as DRESS syndrome (= drug rush with eosinophilia and systemic symptoms), is indicated by the combined occurrence of usually 3-4 symptoms simultaneously (morbilliform to maculopapular exanthema, fever, nausea or vomiting) on average about 11 days after the start of treatment. In one third of the patients the hypersensitivity reaction proceeds without exanthema. Epicutaneous testing often demonstrates sensitization to abacavir. The allele HLA-B5701, which occurs in Caucasians, is positive in up to 90% of HSR and can be determined before starting therapy with abacavir. Re-exposure should be avoided after an HRS.
- Immune reconstitution syndrome (IRIS): Especially patients with an advanced cellular immunodeficiency who start antiretroviral combination therapy are at risk of developing an aberrant, often pathogen-specific immune response. The skin, as a mirror of the immune system, is also frequently affected. In addition to infections (e.g. herpes zoster, herpes simplex, molluscum, HPV-associated changes), multifactorial (psoriasis, acne, eosinophilic folliculitis) and autoimmune-mediated skin changes occur. Antiretroviral therapy should be continued if possible and specific therapy initiated.
- Lipodystrophy syndrome: Lipodystrophy syndrome is the term used to describe fat distribution disorders and metabolic changes in patients on HAART. Loss of subcutaneous adipose tissue is most apparent in the face, extremities, and gluteal. Lipohypertrophy is seen primarily visceral, less commonly nuchal. Associated metabolic changes include insulin resistance, glucose tolerance disorders, diabetes mellitus, hypertriglyceridemia, hypercholesterolemia, and hyperlactatemia. Switching antiretroviral therapy should be considered, and drug treatment of metabolic disorders should take into account interactions with agents of antiretroviral therapy.
- Mitochondrial toxicity: NRTIs in particular can competitively inhibit RNA-dependent DNA polymerase in mitochondria and thus their DNA replication. This results in impairment of mitochondrial enzymes. The thymidine analogues stavudine, and didanosine, in particular, and to a lesser extent zidovudine, are thought to be responsible for this.
- Hyperpigmentation: Rarely, melanonychia striata medicamentosa occurs under zidovudine and emtricitabine.
Complication(s)This section has been translated automatically.
Note(s)This section has been translated automatically.
- Interactions in HIV therapy are manifold and have so far only been rudimentarily investigated. NNRTIs and PIs are largely degraded by the cytochrome P450 system. Drug level measurements should be performed in cases of unclear interaction. Information on interactions with frequently used drugs can be found at www.ifi-interaktions-hotline.de.
- Resistance analyses: Rule-based and data-based interpretation systems are available for the interpretation of genotypic and phenotypic resistance analyses.
- Rule-based interpretation systems:
- HIV-GRADE: http://www.hiv-grade.de/cms/grade/homepage.ht ml
- Stanford database: http://hiv.net/link.php?id=24
- HIV Genotypic Drug Resistance Interpretation - ANRS AC11: http://hiv.net/link.php?id=138
- Los Alamos database: http://hiv.net/link.php?id=25
- Data-based interpretation systems: geno2pheno: http://hiv.net/link.php?id=26.
LiteratureThis section has been translated automatically.
- Esser S, Helbig D, Hillen U, Dissemond J, Grabbe S (2007) HIV-therapy associated side effects. JDDG 5: 745-754
- May MT et al (2006) HIV treatment response and prognosis in Europe and North America in the first decade of highly active antiretroviral therapy: a collaborative analysis. Lancet 368: 451-458
- Salzberger B, Marcus U, Vielhaber B, Arasteh K, Golz J, Brockmeyer NH, Rockstroh J (2004) German-Austrian recommendations for the antiretroviral therapy of HIV infection (status May 2004). Eur J Med Res 9: 491-504
TablesThis section has been translated automatically.
Substance or group of substances |
Trade name |
Most important side effects |
dietary regulation |
Dosage form |
Dose* |
|---|---|---|---|---|---|
Nucleoside reverse transcriptase inhibitors (nucleoside analogues, NRTI) |
|
Hepatic steatosis, rarely lactate acidosis, lipodystrophies syndrome§ |
|
|
|
Abacavir |
Ziagen |
hypersensitivity syndrome |
|
Tablets of 300 mg, juice |
2 times/day 300 mg p.o. |
Didanosine |
Videx |
pancreatitis, neuropathy |
take in soberly |
Capsules of 400 mg, capsules of 250 mg, capsules of 125 mg, powder |
> 60 kg KG: once/day 400 mg p.o. |
< 60 kg bw: once/day 250 mg or twice/day 125 mg p.o. | |||||
Emtricitabine |
Emtriva |
Headaches, gastrointestinal complaints (diarrhoea, nausea) |
|
125 milligram capsules, Solution with 10 mg/ml |
> 4 months and > 33 kg KG: once/day 200 mg p.o. |
Lamivudine |
Epivir |
Headaches |
|
Tablets of 300 mg, tablets of 150 mg, solution |
once/day 300 mg or twice/day 150 mg p.o. |
Stavudine |
Zerit |
neuropathy, pancreatitis |
|
Capsules of 40 mg, capsules of 30 mg |
> 60 kg KG: 2 times/day 40 mg p.o. |
< 60 kg KG: 2 times/day 30 mg p.o. | |||||
Zidovudine |
Retrovir |
Neutropenia, anemia, myopathy |
|
250 mg capsules, juice |
2 times/day 250 mg p.o. |
Combination preparation: lamivudine + zidovudine |
Combivir |
Headache, neutropenia, anaemia, myopathy |
|
Tablets à (150 mg/300 mg) |
2 times/day 150 mg/300 mg p.o. |
Combination preparation: Lamivudine + Abacavir |
Kivexa |
Nausea, headache, gastrointestinal side effects such as vomiting and diarrhoea |
Tablets à (300 mg/600 mg) |
once/day 300 mg/600 mg p.o. |
|
combined preparation: lamivudine + zidovudine + abacavir |
Trizivir |
Headache, neutropenia, anaemia, myopathy, hypersensitivity syndrome |
|
Tablets à (150 mg/ 300 mg/300 mg) |
2 times/day 150 mg/300 mg/300 mg p.o. |
Nucleotidal reverse transcriptase inhibitors (nucleotide analogues, NtRTI) |
|
|
|
|
|
Tenofovir |
Viread |
Gastrointestinal complaints (diarrhoea, nausea) |
|
Tablets of 300 mg |
once/day 300 mg p.o. |
Combination preparation: Emtricitabine + Tenofovir |
Truvada |
Headaches, gastrointestinal complaints (diarrhoea, nausea) |
Take with meal |
Tablets à (200 mg/300 mg) |
once/day 200 mg/300 mg p.o. |
Non-nucleosidal reverse transcriptase inhibitors (NNRTI) |
|
Drug reactions |
|
|
|
Efavirenz***** |
Sustiva, Stocrin |
Psychotropic NW; drug exanthema |
|
Capsules of 200 mg, capsules of 600 mg |
once/day 600 mg p.o. |
Nevirapine**** |
Viramune |
drug exanthema, hepatotoxicity |
|
Tablets of 100 mg |
Initial: 100 mg once/day for 14 days, then dose adjustment to 200 mg p.o. twice/day or 400 mg p.o. once/day. |
Etravirin |
Intelence |
diarrhea, headache, drug anthema, itching |
|
Tablets of 100 mg |
2 times/day 200 mg p.o. |
Protease inhibitors (PI)** |
Glucose intolerance, lipometabolic disorders, lipodystrophy syndrome§ |
|
|
|
|
Atazanavir |
Reyataz |
Diarrhea, headaches, hyperbilirubinemia (icterus) |
Take with meal |
Capsules of 100, 150, 200 mg |
once/day 400 mg p.o. |
Recommendation in combination with ritonavir: once/day 300 mg p.o. + ritonavir once/day 100 mg p.o. | |||||
Darunavir |
Prezista |
Nausea, diarrhoea, hyperlipidemia |
|
Tablets of 400 mg |
2 times/day 600 mg + ritonavir 2 times/day 100 mg p.o. |
Fosamprenavir |
Telzir |
Diarrhoea |
|
Film sheet 700 mg or suspension 50 mg/ml |
2 times/day 1400 mg p.o. |
Recommendation in combination with ritonavir: 2 times/day 700 mg p.o. + ritonavir: 2 times/day 100 mg p.o. Alternatively: 1 time / day 1400 mg p.o. + ritonavir: 1 time / day 200 mg p.o. | |||||
Indinavir |
Crixivan |
nephrolithiasis, hyperbilirubinaemia |
Take on an empty stomach or on a low-fat diet |
Capsules of 400 mg |
As mono PI: 3 times/day 800 mg p.o. |
Recommendation in combination with ritonavir: 2 times/day 400 mg indinavir + 2 times/day 100 mg ritonavir p.o. | |||||
Lopinavir + ritonavir |
Kaletra |
lipometabolic disorders, nausea, diarrhoea |
Take with meal |
Capsules à (133 mg/33 mg), solution |
2 times/day 400 mg p.o. Lopinavir + 2 times/day 100 mg p.o. Ritonavir |
Nelfinavir |
Viracept |
diarrhea, nausea |
Not to be taken sober |
250 mg tablets, powder |
2 times/day 1250 mg p.o. |
Ritonavir |
Norvir |
diarrhea, nausea, hypertriglyceridemia |
|
Capsules of 100 mg, juice |
2 times/day 600 mg p.o.; juice: 2 times/day 7,5 ml p.o. |
Saquinavir |
Invirase*** |
Diarrhoea, nausea (usually mild) |
To be taken with protein- or fat-rich food |
Filmbl. 500 mg |
Recommendation in combination with ritonavir: 2 times/day 1000 mg saquinavir + 100 mg ritonavir p.o. |
Fusion inhibitors/entry inhibitors |
|
Local reactions at the injection site, flu-like symptoms |
|
|
|
Enfuvirtide (T-20) |
Fuzeon |
Reactions at the injection site (erythema, urtica) |
|
hypodermic injection |
2 times/day 90 mg (1 ml) s.c. |
|
* normal kidney function, body weight > 60 kg; ** all protease inhibitors are inhibitors of cytochrome P450; ritonavir is the most potent inhibitor, some isoenzymes are also induced by ritonavir *** use only in combination with ritonavir; **** Possibly increase the lopinavir/ritonavir dose in PI-pretreated patients to 533/133 mg 2 times/day in combination with efavirenz or nevirapin. In general, due to the mutual interactions when combining NNRTIs and PI, dose adjustments and, if necessary, drug monitoring must be considered; ***** different trade names in Germany and Austria; § the pathogenesis of lipodystrophies syndrome is still unclear. Both protease inhibitors and reverse transcriptase inhibitors appear to be involved in the development of the syndrome. | |||||
|
|
I |
II |
III |
|
Graduation of therapy recommendations * |
Based on at least one randomized study with clinical endpoints |
On the basis of surrogate marker studies |
According to experts |
A |
Clear recommendation |
A I |
A II |
A III |
B |
Generally advisable |
B I |
B II |
B III |
C |
Substitutable |
C I |
C II |
C III |
D |
To be rejected in general |
D I |
D II |
D III |
E |
Unambiguous rejection |
E I |
E II |
E III |
* Clinical endpoint studies will no longer be conducted due to the changed FDA and EMEA approval requirements for new substances | ||||
Substance or group of substances and preparations |
Most important side effects |
Dose* |
|---|---|---|
Nucleoside reverse transcriptase inhibitors (nucleoside analogues, NRTI) |
Hepatic steatosis, rarely lactate acidosis, lipodystrophies syndrome§ |
|
Abacavir (Ziagen) |
hypersensitivity syndrome |
2 times/day 300 mg p.o. |
Didanosine (Videx) |
pancreatitis, neuropathy |
> 60 kg KG: once/day 400 mg p.o. |
< 60 kg bw: once/day 250 mg or twice/day 125 mg p.o. | ||
Emtricitabine (Emtriva) |
Headaches, gastrointestinal complaints (diarrhoea, nausea) |
> 4 months and > 33 kg KG: once/day 200 mg p.o. |
Lamivudine (Epivir) |
Headaches |
once/day 300 mg or twice/day 150 mg p.o. |
Stavudine (Zerit) |
neuropathy, pancreatitis |
> 60 kg KG: 2 times/day 40 mg p.o. |
< 60 kg KG: 2 times/day 30 mg p.o. | ||
Zalcitabine (Hivid) |
Neuropathy, oral ulcers |
3 times/day 0.75 mg p.o. |
Zidovudine (retrovir) |
Neutropenia, anemia, myopathy |
2 times/day 250 mg p.o. |
Combination preparation: lamivudine + zidovudine (Combivir) |
Headache, neutropenia, anaemia, myopathy |
2 times/day (150 mg + 300 mg) p.o. |
Combination preparation: Lamivudine + Zidovudine + Abacavir (Trizivir) |
Headache, neutropenia, anaemia, myopathy, hypersensitivity syndrome |
2 times/day 150 mg + 2 times 300 mg + 2 times 300 mg p.o. |
Nucleotidal reverse transcriptase inhibitors (nucleotide analogues, NtRTI) |
|
|
Tenofovir (Viread) |
Gastrointestinal complaints (diarrhoea, nausea) |
once/day 300 mg p.o. |
Non-nucleosidal reverse transcriptase inhibitors (NNRTI) |
Drug reactions |
|
Delavirdin (Rescriptor) |
Drug exanthema |
3 times/day 400 mg p.o. |
Efavirenz (Sustiva, Stocrin) ***** |
Psychotropic NW; drug exanthema |
once/day 600 mg p.o. |
Nevirapine (Viramune) **** |
drug exanthema, hepatotoxicity |
Initial: 100 mg once/day for 14 days, then dose adjustment to 200 mg p.o. twice/day or 400 mg p.o. once/day. |
Protease inhibitors (PI)** |
Glucose intolerance, lipometabolic disorders, lipodystrophy syndrome§ |
|
Amprenavir (Agenerase) |
diarrhea, headache, drug exanthema |
2 times/day 1200 mg p.o. |
Recommendation: Combination with ritonavir 2 times/day 600 mg amprenavir + 2 times/day 100 mg ritonavir p.o. | ||
Atazanavir (Reyataz) |
Diarrhea, headaches, hyperbilirubinemia (icterus) |
once/day 400 mg p.o. |
Recommendation in combination with ritonavir: once/day 300 mg p.o. + ritonavir once/day 100 mg p.o. | ||
Fosamprenavir (Lexiva) |
Diarrhoea |
2 times/day 1400 mg p.o. |
Recommended combination with ritonavir: fosamprenavir: once/day 1400 mg p.o. + ritonavir: once/day 200 mg p.o. | ||
Alternative: Fosamprenavir: 2 times/day 700 mg p.o. + ritonavir: 2 times/day 100 mg p.o. | ||
Indinavir (Crixivan) |
nephrolithiasis, hyperbilirubinaemia |
As mono PI: 3 times/day 800 mg p.o. |
Recommendation in combination with ritonavir: 2 times/day 400 mg indinavir + 2 times/day 100 mg ritonavir p.o. | ||
Lopinavir + ritonavir (Kaletra) |
lipometabolic disorders, nausea, diarrhoea |
2 times/day 400 mg p.o. Lopinavir + 2 times/day 100 mg p.o. Ritonavir |
Nelfinavir (Viracept) |
diarrhea, nausea |
2 times/day 1250 mg p.o. |
Ritonavir (Norvir) |
diarrhea, nausea, hypertriglyceridemia |
2 times/day 600 mg p.o.; juice: 2 times/day 7,5 ml p.o. |
Saquinavir (Invirase***, Fortovase) |
Diarrhoea, nausea (usually mild) |
3 times/day 1200 mg p.o. |
Recommendation in combination with ritonavir: 2 times/day 1000 mg saquinavir + 2 times/day 100 mg ritonavir p.o. | ||
Fusion inhibitors/entry inhibitors |
Local reactions at the injection site, flu-like symptoms |
|
Enfuvirtide (Fuzeon) |
reactions at the injection site (erythema, urtica) |
2 times/day 90 mg (1 ml) s.c. |
|
* normal kidney function, body weight > 60 kg; ** all protease inhibitors are inhibitors of cytochrome P450, ritonavir is the most potent inhibitor, some isoenzymes are also induced by ritonavir *** use only in combination with ritonavir; **** Possibly increase the lopinavir/ritonavir dose in PI-pretreated patients to 533/133 mg 2 times/day in combination with efavirenz or nevirapin. In general, due to the mutual interactions when combining NNRTIs and PI, dose adjustments and possibly drug monitoring must be considered; ***** different trade names in Germany and Austria; § the pathogenesis of lipodystrophies syndrome is still unclear. Both protease inhibitors and reverse transcriptase inhibitors appear to be involved in the development of the syndrome. | ||
Combination partner 1 |
Degree of recommendation |
|
Combination partner 2 |
Degree of recommendation |
Nucleoside/nucleotide combinations |
Recommended is the combination therapy of at least 2 NRTI/NtRTI (combination partner 1) with at least one NNRTI and/or PI (combination partner 2) |
NNRTI |
|
|
Tenofovir/emtricitabineI |
AII |
Efavirenz AII |
AII |
|
zidovudine/lamivudine |
AI |
nevirapine AII |
AII |
|
|
|
|
||
PI |
|
|||
lopinavir/ritonavir |
AII |
|||
Fosamprenavir |
AII |
|||
Combination partner 1 |
Degree of recommendation |
|
Combination partner 2 |
Degree of recommendation |
NRTI combinations of 2 NRTI |
|
Recommended is the combination therapy of at least 2 NRTI (combination partner 1) with at least one NNRTI and/or PI (combination partner 2) |
NNRTI |
|
abacavir/lamivudine |
BII |
Nevirapine |
BII |
|
didanosin/lamivudine |
BII |
|
|
|
Emtricitabine |
BII |
PI |
|
|
|
|
atazanir/ritonavir |
BII |
|
NRTI combinations of 3 NRTI |
|
Atazanavir |
BII |
|
Abacavir/zidovudine/lamivudine * |
BII |
saquinavir/ritonavir |
BII |
|
|
|
nelfinavir/ritonavir |
CII |
|
|
|
indinavir/ritonavir |
CII |
Organ side effects |
causative NRTIs |
Neuromuscular NW |
|
peripheral polyneuropathy |
DDI, d4T |
Myopathy |
AZT |
Cardiomyopathy |
DDI, AZT |
Hepatic and gastrointestinal NW |
|
Steatosis |
all NRTI (d4T >> other NRTI) |
Pancreatitis |
DDI, d4T |
Haematological NW |
|
Anemia, neutropenia |
AZT |
Nephrological NW |
|
proximal tubule dysfunction, hypophosphatemia |
TDF |
Metabolic and adipocyte NW |
|
Lipoatrophy |
d4T > DDI > AZT > ABC > TDF > 3TC > FTC |
hyperlactataemia, lactate acidosis |
d4T > DDI > AZT > ABC > TDF > 3TC > FTC |
Hyperlipidemia |
d4T |
Clinical |
CD4+lymphocytes/µl |
HIV RNA (copies/ml) (RT-PCR) |
Therapy recommendation |
HIV-associated symptoms and diseases (CDC: C, B) |
All values |
|
A I |
Asymptomatic patients (CDC: A) |
< 200 |
All values |
A I |
|
200-350 |
All values |
B II |
|
350-500 |
> 50,000-100,000 copies |
B II |
|
350-500 |
< 50,000 copies |
C III |
|
> 500 |
All values |
C III |
Acute retroviral syndrome |
All values |
All values |
C II |