Principles of newly diagnosed HIV

infection an update

Case
Mr SC was a 43yo male from home who works as a night security guard
Due to get married in 2 weeks to partner of 9 months

Background

Lumbar disc herniation

Biceps detachment

Presentation:

Presented to ED with a 4/7 history of severe left facial pain of sudden onset
Associated with developing vesicular rash along left jaw and hearing impairment
Initially presented to ED yesterday and commenced on oral acyclovir, re-presented today due to
worsening pain and unable to tolerate oral intake
Reports improvement of symptoms since commencing acyclovir

No IVDU, not MSM, one current female partner (unprotected sex), no previous Hx
of STIs for either partner

Nil Medications, NKDA

Case
Physical Examination

T: 38.4C

HR: 91

SaO2: 98% RA

BP: 128/91

Head
Vesicular rash extending across distributions of left mandibular, maxillary
and ophthalmic divisions of CN V
Worst in mandibular division

Ulcerated lesions across left side of tongue and left cheek

Gums inflamed
Vesicles within left external auditory canal tympanic membrane not able to
be visualised
Nil facial muscle weakness
Enlarged left submandibular and pre-auricular lymph nodes
Slit lamp: no dendritic ulcers present in presence of fluorescent light

Case
Assessment
Severe herpes zoster involving all three divisions of the left trigeminal nerve
?Immunodeficiency

Plan

Start IV acyclovir
Amitriptyline
IVT
HIV/hepatitis serology
ENT review for consideration of acyclovir ear drops/antibiotics
ID review regarding oral/IV therapy

Case
Progress (Day 3 of Admission)
Informed by ID Registrar that HIV serology has returned positive
(Western blot has also since returned positive)

Possibility of false positive explained to patient

Revisited history
Has had previous unprotected sex with known female partners only
No high risk contacts (overseas partners or sex workers), IVDU or male sexual partners

HCV/HBV serology negative

ID Outpatients
CD4 count: 457 cells/microlitre
Viral load: 57, 600 copies/mL
Discussed legal implications of knowingly transmitting HIV

HIV Epidemiology
Cost of Zidovudine (AZT)
reduced by 75%

Adapted from the Kirby Institute

HIV Epidemiology

Adapted from the Kirby Institute

Transmission
Type of Exposure

Risk per 10,000 exposures

Blood transfusion

9,250

Needle-sharing (IVDU)

63

Needle-stick injury

23

Receptive anal intercourse

138

Insertive anal intercourse

11

Receptive penile-vaginal intercourse

Insertive penile-vaginal intercourse

Adapted from the Patel et. al. 2014

HIV Testing
SA Pathology:

1.

Third generation enzyme immunoassay (EIA) for anti-HIV antibodies

(Sens: >99% Spec >99% False Pos: 1%)
IF POSITIVE

2.

Confirmatory Western-blot for HIV antibodies

Patients not HIV positive following positive EIA

Should be counselled on safe practices and false positive risk

HIV Testing
The Future:

1.

Fourth generation EIA for anti-HIV antibodies and p24 antigen

IF POSITIVE

2.

Confirmatory HIV-1/HIV-2 antibody differentiation assay

Benefits:
Able to identify acute/early infection due to detection of p24 antigen
Early identification allows early antiretroviral treatment
Reduces risk of pre-seroconversion transmission

HIV-1/HIV-2 differentiation assay HIV-2 rare but requires alternate

treatment

Legal Implications of HIV

Laws vary between states these are those that apply in SA

Notifiable disease requiring contact tracing

Do not need to disclose HIV status as long as all reasonable precautions
against HIV are undertaken

Reasonable precautions untested in court

Condoms likely constitute reasonable precautions
?undetectable viral load
?adherence to anti-retroviral drug regime

Criminal charges may be laid if HIV patient engages in unprotected sex

even if there is no transmission of infection

Treatment
Rationale:
Reduction in HIV-associated morbidity and mortality
Prevention of transmission to sexual partners
Prevention of vertical transmission

Antiretroviral therapy (ART) is recommended for all HIV-infected patients

Strength of evidence decreases as CD4 count increases

Patients must be informed and understand the benefits, risks and especially
adherence to treatment
Initiate therapy in all patients with:
If presence of HIV-associated complications (opportunistic infections, constitutional
symptoms, HIV neurological disease, thrombocytopaenia or nephropathy)
Pregnancy
HBV co-infection
CD4 count <500cells/microlitre

Treatment
Optimal antiretroviral regimen consists of:
2 nucleoside reverse transcriptase inhibitors (NRTI)
AND ONE OF

Non-nucleoside reverse transcriptase inhibitor (NNRTI)

Protease inhibitor (PI) and ritonavir (CYP3A4 inhibitor)
Integrase strand transfer inhibitor (INSTI)

INSTI

NRTI/NNRTI

Fusion Inhibitors

PI

Treatment
Factors to consider when selecting initial
regime:

HIV resistance testing

Pre-treatment HIV viral load
Potential adverse effects
Known or potential drug interactions with
other medications
Comorbid conditions (HCV/HBV, liver/renal
disease)
Patient preference and adherence potential
Adverse effects
Pill burden
Dosing frequency

Optimal antiretroviral regimen consists of:

2 nucleoside reverse transcriptase inhibitors (NRTI)
AND ONE OF
Non-nucleoside reverse transcriptase inhibitor (NNRTI)
Protease inhibitor (PI) and ritonavir
Integrase strand transfer inhibitor (INSTI)

 All regimes show potent virological efficacy

in given patient groups
Regimes vary by:
Adverse effect profile (main barrier to
adherence)
Potential for drug interactions
Pill burden/dosing frequency
Barrier to viral resistance

Goals
Viral load reduction to below limit of detection within 12-24 weeks of
initiation of therapy
Long-term maintenance

Virological failure:
The inability to achieve or maintain suppression of viral replication to <200
copies/mL
Assess adherence, potential drug interactions, drug-resistance
Change to new regime consisting of 3 active anti-retrovirals measure response

Post-Exposure Prophylaxis
The risk of transmission is dependant on the nature of the exposure

If source of HIV antibody/antigen negative and unlikely to be in window

period then no further testing of source or exposed person is necessary
If exposure warrants testing then HIV antibody testing at baseline, 4-6
weeks and 3 months post-exposure

Drug choice for post-exposure prophylaxis (PEP) is influenced by:

Sources antiretroviral treatment history, viral load and drug resistance
Medical history of exposed person

For low risk exposures: double ARV therapy

For high risk exposures: triple ARV therapy

Thank you

References
Australasian Society for HIV Medicine 2014, Antiretroviral Guidelines US DHH Guidelines with Australian Commentary,
ASHM 2014.

Bartlett, J 2014, Screening and diagnostic testing for HIV infection, UpToDate, accessed 26 April 2015.
Electronic Therapeutic Guidelines Australia 2014, Postexposure prophylaxis against bloodborne viruses, eTG 2014.
Fauci, AS, Braunwald, E, Kasper, DL, Hauser, SL, Longo, DL, Jameson, JL & Loscalzo, J 2008, Harrisons principles of internal
medicine, 17th edn, McGraw Hill Medical, New York, NY
HIV/AIDS Legal Centre Incorporated 2013, Disclosing your HIV status A guide to some of the legal issues in South
Australia, halc 2013.
Kirby Institute 2014, HIV in Australia Annual Surveillance Report 2014, Centre for Social Research in Health 2014.
Patel, P, Borkowf, C & Brooks, J 2014, Estimating per-act HIV transmission risk: a systematic review, AIDS, vol. 28. no. 10,
pg. 1509-1519.