HIV Medicine

St.Jamess Hospital, Dublin

Student teaching
2017
 Agenda
Global epidemic
Basic virology
Modes of transmission
Symptoms
Diagnosis
Treatment
 Antiretroviral Therapy: Past,
Present & Future 1. New Drugs

2. NRTI Sparing
regimens
Single The Integrase
era 3. Long acting
Triple drug tablet
agents?
therapy regimens
ZDV
monotherapy

HIV-1
discovered

1983 1987 1996 2006 2012/13 2018ff

 Global epidemic

36.7 million people living with HIV

2.1 million new HIV infections annually
Source: WHO Statistics 2016
35 million deaths since 1981
 HIV in Ireland

512 new diagnoses of HIV in 2016 (11.2/100,000)

75% male
49.7% MSM, 23.8% heterosexual, 9.2% IVDU, <1% MTCT
Many late diagnosis! (45.7% had CD4 T cell count <350 at
diagnosis, 22% <200 )
Source: Health Protection Surveillance Centre
 Basic virology
Virus nucleic acid + capsid
Cannot grow or multiply alone - need a host cell
Attach via specific receptors

Retrovirus
RNA DNA
Enveloped
2x single-stranded RNA
Nucleocapsid proteins
Diagnostic testing
Reverse transcriptase and integrase
enzymes
Drug targets
Infects:
CD4+ T-cells
Macrophages
Dendritic cells
Basic virology
 Serum evaluation
CD4 Count
surrogate measure of stage of disease
Opportunistic infections
CD4 < 500 - shingles, thrush, skin infections,
bacterial infections, TB
Cd4 < 200 - PCP
CD4 <100 MAC +toxoplasmosis
CD4 <50 - CMV

Viral Load

Platelets
Chronic HIV

Modified from Fauci et al., Ann Intern Med 1996;124:654

 Modes of Transmission
Sexual
Anal > Vaginal > Oral
Receptive > Insertive

Intravenous drug use

Needlestick injury

Mother-to-child
In utero
Intrapartum
Breastfeeding

Blood transfusion
 Risk of Transmission
Type of Exposure Risk of HIV Transmission

Blood transfusion 92.5%

Perinatal 10%-50%

Sexual intercourse 0.04-1.4%

Injecting drug use 0.6%

Needle Stick Injury 0.23%

Human Bite negligible

NB- Risk increases with

1. Concurrent STIs (if exposure through sexual means)
2. Higher Viral loads/advanced disease
Patel P, Borkowf CB, Brooks JT. Et al. Estimating per-act HIV transmission risk: a systematic
review. AIDS. 2014.
Pretty LA, Anderson GS, Sweet DJ. Human bites and the risk of human immunodeficiency virus
 Acute HIV
Seroconversion illness

2-4 weeks post exposure, lasts 1-3 weeks

Fever, sweats, fatigue, malaise, arthralgia, myalgia
Maculopapular rash
Generalised lymphadenopathy
Oral and genital ulceration, pharyngitis
Lymphocytic/aseptic meningitis, headache

Most seek medical attention!

 Opportunistic Infections
Pneumocystis jirovecii pneumonia
CD4+ T-cells <200 cells/l
Subacute, progressive dyspnoea, cough
Bilateral infiltrate on CXR
Dx: stain on BAL on bronchoscopy
Tx: co-trimoxazole

Cryptococcal meningitis
Subacute, headache, fever, altered mental status,
meningism, photophobia
CSF: opening pressure, WCC, protein, glucose
Dx: Cryptococcal antigen from CSF
Tx: Amphotericin B /flucytosine, may need regular LPs to
reduce pressure
 Opportunistic Infections
Cerebral toxoplasmosis
CD4+ T-cells <100 cells/l
Neurological signs and symptoms
Multifocal ring-enhancing lesions
Dx: CSF Toxoplasma PRC/serology, bx
Tx: pyrimethamine/sulfadiazine

Disseminated mycobacterium avium -complex

CD4+ T-cells <50 cells/l
Fever, weight loss, fatigue, anaemia, diarrhoea,
hepatosplenomegaly, abdominal pain, lung infiltrates
Elevated ALP
Dx: blood culture/ bone marrow
Tx: clarithromycin, ethambutol, rifabutin
 Opportunistic Infections
CMV - Multisystem disease
Retinitis
Pneumonitis
Oesophagitis
Colitis
CNS, adrenalitis, skin, etc.

CD4+ T-cells <200 cells/l

Fever, fatigue, weight loss, organ-specific symptoms
Dx: histology, CMV PRC
Tx: (val)ganciclovir
 Diagnosis
HIV Antibody
ELISA detects antibodies to HIV
4th generation (HIV Ab/P24 ag) usually positive within 4
weeks
Western Blot
Confirmatory test detects antibodies to specific protein
HIV PCR = Viral load
Detects and quantifies viral RNA
Limited use for primary diagnosis
Rapid point-of-care testing
Buccal swabs opportunistic screening
CD4+ T-cell count
No use for diagnosis
Anti-Retroviral Therapy

1. Fusion Inhibitors
(T20), CCR5
Antagonists
(Maraviroc)
2. NRTI/ NNRTI
3. Integrase Inhibitors
4. Protease Inhibitors
5. Maturation Inhibitors
 Antiretroviral Therapy
NRTIs NNRTIs Protease Integrase Entry
Inhbitors Inhibitors Inhibitors
Tenofovir Efavirenz Atazanavir Raltegravir Maraviroc

Abacavir Nevirapine Darunavir Dolutegravir

Lamivudine Etravirine Lopinavir Elvitegravir

Emtricitabine Rilpivirine Tipranavir

Zidovudine Delavirdine (Fos)amprenavir Fusion

Inhibitors
Stavudine Saquinavir Enfuvirtide

Didanosine Nelfinavir

Zalcitabine Indinavir

Ritonavir
 Prognosis in cART era
Lifetime expectancy is same as for general population1

Poor prognostic predictors:

Older age at diagnosis2,3
Male gender2,3
Black / Hispanic ethicity2,4
Late treatment initiation (CD4 <200)2,3
Premature ART discontinuation2
Injection drug use5
1. Van Sigheim AIDS 2010;24:1527-35
2. Losina CID 2009;49:1570-78
3. May Lancet 2010;376:449-457
4. Harrison JAIDS 2010;53:124-130
5. Lloyd-Smith AIDS 2006;20:445-50
 When to start?
Traditionally
CD4+ T Cell < 350
Symptomatic HIV
Pregnancy
Post Exposure Prophylaxis (short term use)

However:
START trial 2015
Those on treatment had lower rates of illness and hospitalisations
regardless of CD4 count

ART for all HIV+ Patients regardless of CD4 count

Source: European AIDS Clinical Society Guidelines 2014

 Goal of cART
Suppress viral replication as much as possible = HIV
RNA to be undetectable (<40copies/ml)

CD4 cells >200 cells/l

Allow recovery of immune system

Choice of regime depending on lifestyle factors/

compliance/ tolerance/side effects

Viral replication in the presence of drug = resistance

 Post-Exposure Prophylaxis
PEP
Risk of infection depends on:
Viral load / clinical stage of source
Gauge of needle / hollow or solid
Amount of blood
Gloves worn?
Use of cART within 72 hours of exposure to HIV
Sooner the better
4 weeks of therapy recommended
Repeat bloods at 1 and 3 months
 Pre-Exposure Prophylaxis
PrEP / PrEPc
Taking a dose of ARVs before potential HIV exposure
High risk populations
PROUD/ Ipergay Studies
Significantly Reduced numbers contracting HIV
Truvada (Tenofovir-Emtricitabine) currently lienced in US
for use as PREP
Needlestick Injury Dos and Donts
Always wear gloves
Never sheath needles
Always have sharps disposal bin handy
Ensure HBV vaccination, know your HbsAb status

Wash exposed site immediately with soap and water

Flush mucous membranes with water
Avoid alcohol, hydrogen peroxide, Betadine etc.
Dont milk/squeeze/suck the wound
promotes hyperemia and inflammation at the wound site,
potentially increases systemic exposure to HIV
Contact OH
Test source
Attend A&E or GUIDe clinic for PEP assessment
asap, <72hrs!