sábado, 1 de diciembre de 2018

AIDS Treatment

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By Ananya Mandal, MDReviewed by April Cashin-Garbutt, MA (Cantab)

Infection with Human Immunodeficiency virus or HIV leads to AIDS (Acquired immunodeficiency syndrome) which is mostly fatal and has no cure. AIDS occurs at a later stage in the disease.

At present, HIV positive patients are managed with antiretroviral drugs that prevent the replication of the virus within the body and delay the onset of AIDS. In addition, opportunistic infections in AIDS may be prevented by using drugs targeted against the organisms and the cancers.

History of HIV treatment

Initially in the late 1980s, monotherapy with zidovudine was the only anti-retroviral therapy (ARV). By 1996 more drugs emerged against HIV and combination therapies became more widely used. This highly active combination therapy is now known as highly active anti-retroviral therapy (HAART).

Drug classes

The ARVs mainly act on an enzyme called reverse transcriptase. This enzyme helps in multiplication of the viral particles. The drugs inhibit this enzyme and prevent the viral replication. There are four main classes of drugs that are used as anti-retroviral agents:

Nucleoside reverse transcriptase inhibitors (NRTIs)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Protease inhibitors
Ribonucleotide reductase inhibitor

The drugs, along with their possible side effects, are shown in the table below:

Drug Category	Drug Hame	Toxicity
Nucleoside reverse transcriptase inhibitors (NRTI)	Zidovudine (AZT)	Hepatic steatosis, lactic acidosis, myopathy, cardiomyopathy, dyshaemopoiesis (anaemia, macrocytosis, neutropaenia)
	Didanosien (ddI), Stavudine (d4T)	Hepatic steatosis, lactic acidosi, pancreatitis, myopathy, peripheral neuropathy, dyshaemopoiesis, gynaecomastia
	Lamivudine (3TC)	Dyshaemopoiesis
Non-Nucleoside reverse transcriptase inhibitors (NNRTI)	Nevaripine, Efavirenz	Skin rashes, Stevens-Johnson syndrome, hepatitis
Protease inhibitors (PI)	Saquinavir, Ritonavir, Indinavir, Nefinavir	Lipodystrophy, hyperglycaemia, hyperlipidaemia, hepatitis
Ribonucleotide reductase inhibitor (RNR)	Hydroxyurea	Bone marrow suppression, mouth ulcers, hepatitis

Management of HIV positive patients

Management of HIV positive patients according to the British HIV Association (BHIVA) guidelines:

All patients with HIV infection need antiretroviral therapy if they have a CD4 cell count of below 350 cells/mm3 or signs of nervous system involvement. If an AIDS defining condition is present therapy may be indicated despite normal CD4 levels.
If CD4 cell counts are 351-500 cells/mm3 patients require treatment if they have Hepatitis B or C infection, low percentage of CD4 cells (less than 14%) and have a high risk of heart disease.
Those with late-stage HIV need ARV except in presence of tuberculosis when CD4 cell counts are more than 350 cells/mm3

How is therapy begun and maintained?

Initial therapy is with three drugs: efavirenz plus tenofovir or abacavir, plus lamivudine or emtricitabine

Patients need vaccination against hepatitis B, pneumococcal disease and Haemophilus influenzae type b (and possibly influenza and hepatitis A). Live viral or organism vaccines like BCG, yellow fever, oral typhoid or live oral polio immunisations should not be administered to these patients.

Those with a risk of opportunistic infections need preventive antifungal or antibiotic agents.

How to manage accidental exposure to HIV infection?

This scenario is common among healthcare workers and those who take care of HIV positive patients. There may be an accidental needle stick injury or exposure to HIV contaminated blood or body fluids of the patients.

Those who have been exposed to the virus within the last 72 hours (three days) need to take anti-HIV medication to possibly prevent the infection.

This is called post-exposure prophylaxis or PEP. PEP must be started within 72 hours of coming into contact with the virus. The quicker PEP is started the better - ideally within hours of coming into contact with HIV.

PEP is a month-long treatment with a combination of antiretroviral drugs, which has serious side effects and does not guarantee absolute protection.

HIV infection in pregnancy

Anti retroviral drugs given to pregnant women with HIV helps to prevent passing on the infection to the child. Without treatment, there is a one in four chance that the baby will develop the infection. With treatment, the risk is less than one in a hundred.

Breastfeeding is not recommended in women with HIV since the virus can infect the baby via breast milk.

Patients who wish to get pregnant via artificial techniques need special measures like sperm washing etc. to prevent the infection in the father from passing on to the mother and the baby.

HIV vaccine

Efforts are in place to develop a vaccine against this infection. However, to date there is no approved vaccine against the infection as HIV 1 virus forms a difficult target against which a vaccine may be developed.