Treatment of HIV

Question 1

Aims of ART

Answer 1

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

Question 2

HIV lifecycle

Answer 2

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

Question 3

Classes of ARTs

Answer 3

NRTIs (nucleoside reverse transcriptase inhibitors)
NNRTIs (non-nucleoside reverse transcriptase inhibitors)
PIs (protease inhibitors). Integrase inhibitors. Entry inhibitors. Boosters

Question 4

NRTIs (nucleoside reverse transcriptase inhibitors) 7

Answer 4

Abacavir (ABC). Tenofovir (TDF). Emtricitabine (FTC). Lamivudine (3TC)
Didanosine (DDI). Stavudine (D4T). Zidovudine (AZT)

Question 5

NNRTIs (non-nucleoside reverse transcriptase inhibitors) 4

Answer 5

Efavirenz
Nevirapine
Rilpivirine
Etravirine

Question 6

PIs (protease inhibitors) 8

Answer 6

Darunavir Indinavir
Atazanavir Nelfinavir
Lopinavir Saquinavir
Fos-Amprenavir Tipranavir
All end in -navir

Question 7

Integrase inhibitors 3

Answer 7

Raltegravir
Elvitegravir
Dolutegravir
All end in -gravir

Question 8

Entry inhibitors

Answer 8

Fusion inhibitors –> Enfuviride (T20)

CCR5 inhibitors –> Maraviroc

Question 9

Boosters

Answer 9

Ritonavir ( a PI)

Cobicistat

Question 10

HAART includes

Answer 10

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)

Question 11

Ritonavir

Answer 11

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

Question 12

Why use triple therapy?

Answer 12

Prevents rapid selection of resistant variants

Successful suppression of replication means that less mutation happens

Question 13

Short term side effects of ART

Answer 13

GI intolerance (PIs)     Hypersensitivity (Abacvir)
CNS side effects (Efavirenz) 
Hepatotoxicity (nevirapine)
Skin rashes--> SJS (NNRTIs)
Hyperbilirubinaemia (Atazanavir)

Question 14

Long Term Toxicities of ART

Answer 14

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

Question 15

ART interactions

Answer 15

Induction or inhibition of p450s–>may need to change dose

Drugs to worry about–> rifampacin, phenytoin, asthma drugs (ritonavir potentiates), statins, recreational (MDMA)

Question 16

When do you start HAART?

Answer 16

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

Question 17

Benefits of starting HAART early

Answer 17

Avoid the <200 danger zone
better CD4 recovery
Prevent non-AIDs illness eg MI/CVA due to immune activation and inflammation

Question 18

Factors to consider when prescribing HAART

Answer 18

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)

Question 19

Monitoring on HAART

Answer 19

CD4 count is most important –>measures immune recovery
VL–> should be undetectable
FBC, liver and renal screen, lipids

Question 20

Virological failure

Answer 20

When the VL starts to rise due to viral resistance,
poor compliance or absorption, concurrent illness or drug interactions.
Super-infection

Question 21

Adherence to HAART

Answer 21

General adherence to low term medications is 1/3 to 1/2–> more important for HAART–> should never miss doses
Poor compliance drives resistance

Question 22

Transmission of Infection

Answer 22

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

Question 23

Mother to child transmission

Answer 23

34% if nothing is done and breast feeding
20% if not breast feeding
<1% if not breast feeding and on HAART

Question 24

Post exposure prophyaxis (PEP)

Answer 24

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

Question 25

Efficacy of PEP

Answer 25

81% reduction in infection post occupational exposure | Also some evidence for PSPSE and for preventing vertical transmission

Question 26

When should you take PEP

Answer 26

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

Question 27

How do you PEP?

Answer 27

Start within 72hrs and take for 28 days | 2 NRTI drugs (Truvada and Kaletra)

Question 28

Important considerations when giving PEPSE

Answer 28

``` 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 ```

Question 29

MAC infection in HIV

Answer 29

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.

Question 30

Treatment of CNS Toxoplasmosis in HIV

Answer 30

Pyrimethamine plus sulphadiazine

Question 31

Treatment of intestinal cyclosporiasis

Answer 31

Co-trimoxazole

Question 32

Treatment of cryptococcal meningitis

Answer 32

Amphotericin B plus flucytosine

Question 33

Treatment of Babesia microti in immunologically compromised

Answer 33

IV clindamycin plus quinine

Question 34

Treatment of microsporidiosis

Answer 34

Albendazole