Treatment of HIV Flashcards
Aims of ART
Reduce HIV replication to achieve an undetectable viral load
To restore the immune system and increase CD4 count
To reduce the transmission of HIV infection
HIV lifecycle
All viruses are obligate intracellular parasites, and HIV uses reverse transcriptase to convert RNA to proviral DNA which is replicated by the cell when it activates
Classes of ARTs
NRTIs (nucleoside reverse transcriptase inhibitors)
NNRTIs (non-nucleoside reverse transcriptase inhibitors)
PIs (protease inhibitors). Integrase inhibitors. Entry inhibitors. Boosters
NRTIs (nucleoside reverse transcriptase inhibitors) 7
Abacavir (ABC). Tenofovir (TDF). Emtricitabine (FTC). Lamivudine (3TC)
Didanosine (DDI). Stavudine (D4T). Zidovudine (AZT)
NNRTIs (non-nucleoside reverse transcriptase inhibitors) 4
Efavirenz
Nevirapine
Rilpivirine
Etravirine
PIs (protease inhibitors) 8
Darunavir Indinavir
Atazanavir Nelfinavir
Lopinavir Saquinavir
Fos-Amprenavir Tipranavir
All end in -navir
Integrase inhibitors 3
Raltegravir
Elvitegravir
Dolutegravir
All end in -gravir
Entry inhibitors
Fusion inhibitors –> Enfuviride (T20)
CCR5 inhibitors –> Maraviroc
Boosters
Ritonavir ( a PI)
Cobicistat
HAART includes
2 NRTIs and 1 PI OR 1 NNRTI OR 1 Integrase inhibitor
1 pill–>Atripla (efavirenz+Tenofovir+Emtricitabine(FTC))
BHIVA guidelines recommend Tenofovir + FTC+atazanavir/r)
Ritonavir
Originally used as an PI ART but it caused massive GI problems but it was found to inhibit P450s and so is not used at a lower dose to potentiate other PI ARTs
Why use triple therapy?
Prevents rapid selection of resistant variants
Successful suppression of replication means that less mutation happens
Short term side effects of ART
GI intolerance (PIs) Hypersensitivity (Abacvir) CNS side effects (Efavirenz) Hepatotoxicity (nevirapine) Skin rashes--> SJS (NNRTIs) Hyperbilirubinaemia (Atazanavir)
Long Term Toxicities of ART
Fat redistribution–>previously lipoatrophy but not lipohypertrophy
Metabolic abnormalities–> Diabetes, increased lipids (PIs)
Risk of renal damage or reduced bone density (tenofovir)
Mitochondrial toxicity–>Peripheral neuropathy, liver steatosis, myopathy, lactic acidosis (NRTIs), pancreatitis
ART interactions
Induction or inhibition of p450s–>may need to change dose
Drugs to worry about–> rifampacin, phenytoin, asthma drugs (ritonavir potentiates), statins, recreational (MDMA)
When do you start HAART?
When CD4 is below 350 (low)
When there is any AIDs defining illness
When there is any neurological involvement
Any related STI or cancers requiring treatment
If they have an HIV neg partner
Benefits of starting HAART early
Avoid the <200 danger zone
better CD4 recovery
Prevent non-AIDs illness eg MI/CVA due to immune activation and inflammation
Factors to consider when prescribing HAART
Sequence the virus to assess the resistances
Potency and durability and Patient adherence
Tolerability, safety and side effects
Co-morbidities, viral load and CD4 count
Patient genetics (HLA B57 01)
Monitoring on HAART
CD4 count is most important –>measures immune recovery
VL–> should be undetectable
FBC, liver and renal screen, lipids
Virological failure
When the VL starts to rise due to viral resistance,
poor compliance or absorption, concurrent illness or drug interactions.
Super-infection
Adherence to HAART
General adherence to low term medications is 1/3 to 1/2–> more important for HAART–> should never miss doses
Poor compliance drives resistance
Transmission of Infection
96% reduction of transmission if on ART
Post-exposure prophylaxis is important and often used
Pre-exposure prophylaxis is an issue of ongoing research–> mixed results in studies
Mother to child transmission
34% if nothing is done and breast feeding
20% if not breast feeding
<1% if not breast feeding and on HAART
Post exposure prophyaxis (PEP)
Use of ARTs immediately after exposure (occupational or sexual) to reduce risk of infection
72hr window between exposure and infection where PEP is useful before HIV has got to lymph nodes.
Can be used up to five days after exposure but evidence is less good
Efficacy of PEP
81% reduction in infection post occupational exposure
Also some evidence for PSPSE and for preventing vertical transmission
When should you take PEP
Any form of vaginal or anal where there is a detectable viral load–> if VL is undetectable or status unknown still take if receiving anal sex
Also oral if seman was happening and when needlestick if VL is detectable–> with needle stick better safe than sorry
How do you PEP?
Start within 72hrs and take for 28 days
2 NRTI drugs (Truvada and Kaletra)
Important considerations when giving PEPSE
confirm HIV neg status at baseline Renal and liver monitoring for 2 weeks HIV test at 6 and 12 weeks Use condoms until clear at 12 week stage Inform pt of unlicensed usage and SEs
MAC infection in HIV
Disseminated if CD4 <50. Present with Fever, sweating, malaise, dyspnoea, diarrhoea, weight loss with wasting, pallor.
Can have lymphadenopathy, pallor, tender hepatosplenomegaly and cutaneous involvement.
Treatment of CNS Toxoplasmosis in HIV
Pyrimethamine plus sulphadiazine
Treatment of intestinal cyclosporiasis
Co-trimoxazole
Treatment of cryptococcal meningitis
Amphotericin B plus flucytosine
Treatment of Babesia microti in immunologically compromised
IV clindamycin plus quinine
Treatment of microsporidiosis
Albendazole
