Flashcards in GUM - Management of HIV Deck (20):
How can opportunistic infections be avoided in HIV?
Effective ART is the best protection, but other protective measures remain important:
- Avoidance of contaminated water
- Barrier contraception
- Avoidance of animal-borne infection(cats)
- Malaria vector control in endemic areas
- Co-trimoxazole prophylaxis: protects against Pneumocystis, toxoplasmosis and Isospora belli
- Vaccination against pneumococcus, seasonal influenza and hepatitis B is useful once CD4 counts are >200 cells/mm3.
How is HIV infection treated?
Highly active anti-retroviral therapy (HAART) involves a combination of at least three drugs, typically two nucleoside reverse transcriptase inhibitors (NRTI) and either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). This combination both decreases viral replication but also reduces the risk of viral resistance emerging.
When should HAART be started?
Following the 2015 BHIVA guidelines it is now recommended that patients start HAART as soon as they have been diagnosed with HIV, rather than waiting until a particular CD4 count, as was previously advocated.
What is the mechanism of action of nucleoside reverse transcriptase inhibitors?
NRTIs inhibit the action of the viral reverse transcriptase of HIV viruses. Most of these drugs are phosporylated by host cell enzymes to produce triphosphate compounds that interfere with viral DNA synthesis.
Examples include: zidovudine (AZT), didanosine, lamivudine, stavudine, zalcitabine
How are NRTIs administered?
They are usually given orally, but can be given by IV infusion. The concentration in the CSF is 65% of the blood level.
What are the adverse side effects associated with NRTIs?
general NRTI side-effects: peripheral neuropathy
zidovudine: anaemia, myopathy, black nails
What is the mechanism of action of non-nucleoside reverse transcriptase inhibitors?
Inhibits the action of the viral reverse transcriptase of the immunodeficiency virus. Active against HIV-1 but not HIV-2. They do so by binding to and denaturing the viral reverse transcriptase enzyme. NNRTIs are particularly good at reducing maternal to foetal transmission.
Examples include: nevirapine, efavirenz
How can NNRTIs be administered?
These can only be given orally. The concentration in the CSF is approximately 45% of plasma level.
What side effects are associated with NNRTIs?
Hepatotoxicity. Rash, Stevens-Johnson syndrome. Less common: GIT disturbances, myalgia. Efavirenz can cause disturbances of sleep and dreaming.
What is the mechanism of action of protease inhibitors?
These agents reversibly inhibit the viral specific protease that, during assembly and budding, cleavers precursor viral proteins to give the structural and functional proteins of the new virions.
Examples include: indinavir, saquinavir
How are protease inhibitors administered?
Given orally but subject to extensive first pass metabolism*.
*Remember first pass metabolism means that 90% of the active drug is metabolised during its first pass through the liver
What adverse effects are associated with protease inhibitors?
side-effects: diabetes, hyperlipidaemia, buffalo hump, central obesity, P450 enzyme inhibition
indinavir: renal stones, asymptomatic hyperbilirubinaemia
ritonavir: a potent inhibitor of the P450 system
How can adherence to lifelong treatment in HIV be improved?
Disclosure of HIV status
Joining support groups
Patient nominated treatment supporters
Management of co-existing depression and substance abuse
How should treatment be monitored?
Treatment should be monitored by measuring viral load, which should drop tenfold in the first 4–8 wks of ART. Within 6 mths, viral load should be below the limit of detection (usually < 50 copies/mL). Treatment failure is defined as a subsequent rise to >400–1000 copies/mL. CD4 count rises with treatment and falls with treatment failure, and can be used for monitoring in countries where viral load is unavailable.
How common is HIV infection in pregnancy?
With the increased incidence of HIV infection amongst the heterosexual population there are an increasing number of HIV positive women giving birth in the UK. In London the incidence may be as high as 0.4% of pregnant women. The aim of treating HIV positive women during pregnancy is to minimise harm to both the mother and fetus, and to reduce the chance of vertical transmission.
What factors reduce vertical transmission?
maternal antiretroviral therapy
mode of delivery (caesarean section)
neonatal antiretroviral therapy
infant feeding (bottle feeding)
Should women be screened for HIV?
NICE guidelines recommend offering HIV screening to all pregnant women
How is HIV in pregnancy managed?
1) All pregnant women should be offered antiretroviral therapy regardless of whether they were taking it previously
2) Mode of delivery:
- vaginal delivery is recommended if viral load is less than 50 copies/ml at 36 weeks, otherwise caesarian section is recommended
- a zidovudine infusion should be started four hours before beginning the caesarean section
What anti-retroviral therapy should the neonate be offered if borne to a HIV infected mother?
Zidovudine is usually administered orally to the neonate if maternal viral load is <50 copies/ml. Otherwise triple ART should be used. Therapy should be continued for 4-6 weeks.
Women should not breast feed.