Highly active antiretroviral therapy

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The term highly active antiretroviral therapy (abbreviated HAART for English highly active antiretroviral therapy ) refers to an introduced in 1996, combination therapy of at least three different anti-retroviral drugs (ARVs) to treat HIV infection, if untreated, is almost always to the onset of AIDS leads. Recently, the more neutral and therefore more correct term antiretroviral combination therapy (cART, combined antiretroviral therapy ) has been used instead of HAART .

Concept / advantages / effect

In the highly active antiretroviral therapy, the HIV patient i. d. Usually treated with a combination of three antiretroviral agents from at least two classes of agents. Established therapy schemes consist of the combination of two nucleoside reverse transcriptase inhibitors (NRTI) with a non-nucleoside reverse transcriptase inhibitor (NNRTI) or with an integrase inhibitor (INI) or with a protease inhibitor (PI), whose pharmacological effectiveness is determined by a small dose of ritonavir or cobicistat is increased ("booster"). Successful HAART inhibits virus replication to such an extent that HIV can no longer be detected with the usual diagnostic methods (“below the detection limit”), but it cannot completely prevent it. Reducing the viral load through antiretroviral therapy reduces the risk of AIDS progression , regression of HIV-related symptoms, and long-term, if not always complete, recovery of the immune system (immune reconstitution). HAART thus lowers the mortality of HIV-positive patients from both HIV-related and non-HIV-related causes of death (liver, heart, cancer).

The regular HIV test using ELISA and Western blot remains positive in HAART patients, as antibodies are detected here. The number of viruses sometimes drops from 1.5 million per milliliter of blood to levels that can no longer be detected (less than 20 virus copies / milliliter), but this should not be confused with a cure. The life expectancy of patients with combination therapy gradually equates to normal life expectancy. A normal life is (almost) possible, although individual more aggressive forms and an increasing resistance problem should not be negated. It must therefore be emphasized that so far there is no alternative to infection protection (keyword safer sex ).

If a person's viral load drops to 200 copies / ml or less due to HAART, it is called "virological (or also viral) suppression". Virological suppression prevents the sexual transmission of HIV and at the same time improves the health of people with HIV. Studies show that virologically suppressed people cannot transmit HIV to sexual partners. HAART can lower a person's viral load so much (below 40 virus copies / ml) that it can no longer be detected with the usual tests. It is then said that this person has an “undetectable viral load”, which prevents the sexual transmission of HIV while improving the health of the person with HIV. HAART cannot completely remove HIV infection from the body or cure it. In order to achieve an undetectable viral load, a high level of therapy compliance (taking the HAART according to the instructions) is important.

The likelihood of transmission of the HI virus from mother to her newborn child (mother-to-child transmission of HIV, vertical transmission) can also be a. can be significantly reduced through the use of several antiretroviral agents. The combination of the following measures in Germany has resulted in the mother-to-child transmission rate being reduced from up to 40% to 1–2% since 1995:

  • Controlled birth of the child by caesarean section
  • Treating the mother with antiretroviral drugs before and during delivery
  • Treating the newborn with antiretroviral drugs in the first few weeks after birth
  • Weaning

New developments

Since patients who do not take the antiretroviral drugs correctly can develop long-term resistance even under HAART , medical research is continuously looking for new active ingredients from the known substance classes (NRTIs, NNRTIs, PIs) and for drugs with new mechanisms of action against HIV . In Germany, for example, the first fusion inhibitor (T20 = Enfuvirtide) was approved in 2003 and the entry inhibitor maraviroc and the integrase inhibitor raltegravir were approved in 2007 . These new substances expand the therapeutic options for HI viruses with resistance to older antiretroviral agents. Despite these advances, there is still a need for new drugs.

Side effects

In general, most patients tolerate antiretroviral therapy well for years. Nevertheless, mild side effects such as gastrointestinal complaints are frequent, especially at the beginning of treatment. Adherence problems, changes or discontinuations of therapy can be the result of side effects. Therefore, when starting therapy, it is necessary to prepare the patient for any side effects and possible treatment of the symptoms. It can be difficult to tell whether a symptom is caused by HIV infection or by antiretroviral therapy.

  • Gastrointestinal side effects: Gastrointestinal symptoms such as bloating, loss of appetite, diarrhea, nausea and vomiting are among the most common side effects of HAART. They can occur with almost all antiretroviral drugs, especially in the early stages.
  • Liver toxicity: Slight increases in liver values ​​are common with HAART, severe liver damage occurs in up to 6% of patients. Liver failure is very rare. The hepatotoxicity is common in patients with pre-damage of the liver (viral hepatitis, alcohol abuse, metabolic damage).
  • Renal complications: Tenofovir can cause renal side effects : Severe cases are rare, but a significant number of patients develop renal dysfunction (increase in serum creatinine , acute kidney failure , nephrogenic diabetes insipidus, etc.). Kidney problems can also occur with the protease inhibitor indinavir : About 10% of patients develop x-ray negative nephrolithiasis with renal colic. Kidney stones can also occur with atazanavir , but much less often than with indinavir.
  • Neuropathies : Peripheral polyneuropathies are mainly caused by stavudine and didanosine , which are normally no longer part of a HAART.
  • CNS side effects: With efavirenz , up to 40% of patients experience central nervous symptoms such as dizziness, sleep disorders and nightmares, but also mood swings, depression, changes in personality and suicidal ideation . They are observed especially in the first days and weeks; Discontinuation of therapy is necessary in only 3% of patients.
  • Allergies : Allergies with HAART are common, especially with NNRTIs, with abacavir and the PIs fosamprenavir , atazanavir , tipranavir and darunavir contain a sulfonamide content , so they should be given with caution in sulfonamide allergy .
  • Lactic acidosis : Compared to asymptomatic hyperlactaemia , which occurs in 15–35% of patients treated with NRTIs, lactic acidosis is a very rare but life-threatening complication. It occurs more frequently with stavudine and didanosine , less often with zidovudine , abacavir and lamivudine .
  • Lipodystrophy Syndrome: Lipodystrophy syndrome is a complex of symptoms that includes disorders of fat distribution and metabolic changes. In principle, it can occur with almost all drug combinations, but is found much less often among the therapy combinations used today. The protease inhibitors in particular are responsible for the metabolic changes.

The metabolic changes are complex and can manifest as insulin resistance , glucose tolerance disorders, diabetes mellitus , hypertriglyceridemia , hypercholesterolemia , increased free fatty acids and low “ high-density lipoprotein ” (HDL). Often these metabolic phenomena precede a clinical fat distribution disorder. The fat distribution disorders include a loss of subcutaneous fat tissue (lipoatrophy), especially in the face, buttocks and extremities. Subcutaneous fat loss can occur in isolation or with central obesity. Atypical fat pads on the neck (“ bull's neck ” or “ buffalo hump ”) or on the stomach are less common . In both women and men, there may be (sometimes asymmetrical) enlargement of the breasts. The physical changes can have an adverse effect on the patient's quality of life and adherence.

Other problems from HAART:

See also

literature

  • MT May, JA Sterne, D. Costagliola, CA Sabin, AN Phillips, AC Justice, F. Dabis, J. Gill, J. Lundgren, RS Hogg, F. de Wolf, G. Fätkenheuer, S. Staszewski, Monforte A. D'Arminioo, M. Egger: HIV treatment response and prognosis in Europe and North America in the first decade of highly active antiretroviral therapy: a collaborative analysis. In: The Lancet. 368, No. 9534, 2006, pp. 451-458, doi: 10.1016 / S0140-6736 (06) 69152-6 , PMID 16890831 , deanesmay.com (PDF).
  • RB Reisler, C. Han, WJ Burman, EM Tedaldi, JD Neaton: Grade 4 events are as important as AIDS events in the era of HAART. In: J Acquir Immune Defic Syndr. 34, No. 4, 2003, pp. 379-386, PMID 14615655 .
  • Monforte A. d'Arminio, CA Sabin, A. Phillips, J. Sterne, M. May, A. Justice, F. Dabis, S. Grabar, B. Ledergerber, J. Gill, P. Reiss, M. Egger: The changing incidence of AIDS events in patients receiving highly active antiretroviral therapy. In: Archives of Internal Medicine. 165, No. 4, 2005, pp. 416-423, doi: 10.1001 / archinte.165.4.416 , PMID 15738371 , ama-assn.org (PDF).

Web links

Individual evidence

  1. ↑ S2k guideline : Antiretroviral therapy of HIV infection , AWMF register number 055/001, awmf.org (PDF), as of 05/2014.
  2. ↑ I Kousignian et al .: Effect of HAART, CD4 Cell Counts, and Viral Load on Incidence of AIDS-defining events . Abstract 592. 12th CROI, 22.-25. February 2005.
  3. ↑ Sterne J Boston et al .: Long-term Effect of HAART in Preventing AIDS and Death Compared with No Treatment and with Dual Therapy: The Swiss HIV Cohort Study . Abstract 591.12.CROI, 22.-25. February 2005, Boston.
  4. ↑ Rainer Weber u. a .: HIV and non-HIV-related deaths and their relationship to immunodeficiency: the D: A: D Study. In: 12th conference on retroviruses and opportunistic infections. 2005.
  5. ↑ German-Austrian recommendations on HIV therapy in pregnancy and in newborns exposed to HIV - as of September 2011 ( Memento of the original from March 7, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. (PDF; 207 kB), last accessed on January 26, 2014.  @1@ 2Template: Webachiv / IABot / www.rki.de
  6. ↑ Christian Hoffmann, Jürgen K. Rockstroh (eds.): HIV 2013/2014 . (PDF), accessed on January 26, 2014.