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HIV Diagnosis and Treatment
Jakob Nilsson MD, PhD
Karolinska Institutet
When to suspect HIV?
When to suspect HIV?
When to suspect HIV?
When to suspect HIV?
Bottieau E et al. Fever after a stay in the
tro...[PMID: 18645519]
Matteelli A et al. Sexually transmitted
diseases...[PMID: 11264035]
How to find HIV
Ferrantelli F., et al., Curr Opin Immunol. 14: 495 (2002).
How to find HIV
Ferrantelli F., et al., Curr Opin Immunol. 14: 495 (2002).
Acute retroviral syndrome
 Incubation time 12-16
days
 ~70% have symptoms
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Fever
Sore throat
Lymphadenopathy
Rash, macupapular on upper body
Mucosal ulcers
Gastrointestinal symptoms
Enlarged liver/spleen
Meningitis
Case
 A 31 year old male, visited Phuket, Thailand for 2
weeks on vacation and stayed the last days in
Bangkok. Falls ill 16 days after arriving back in
Stockholm with fever, sore throat and a
macupapular rash.
Case
 A 31 year old male, visited Phuket, Thailand for 2
weeks on vacation and stayed the last days in
Bangkok. Falls ill 16 days after arriving back in
Stockholm with fever, sore throat and a
macupapular rash.
 As further epidemiological questions are asked the
patient informs that he had a condom rupture while
having intercourse with a prostitute in Bangkok.
Case
 A 31 year old male, visited Phuket, Thailand for 2
weeks on vacation and stayed the last days in
Bangkok. Falls ill 16 days after arriving back in
Stockholm with fever, sore throat and a
macupapular rash.
 As further epidemiological questions are asked the
patient informs that he had a condom rupture while
having intercourse with a prostitute in Bangkok.
 Diagnostics?
HIV testing
HIV testing
HIV testing
Antigen
Antibody
(serology)
How to find HIV
Ferrantelli F., et al., Curr Opin Immunol. 14: 495 (2002).
Chronic asymptomatic HIV infection
 How to find patients during the chronic
asymptomatic phase.
 Look in groups with high HIV prevalence.
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Prejudice?
 Signs
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Anemia
Trombycytopenia
Leukopenia
“Zoster too early or too much”
How to find HIV
Ferrantelli F., et al., Curr Opin Immunol. 14: 495 (2002).
AIDS
 How to find patients with AIDS.
 Look for opportunistic infections.
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Tuberculosis
Candida esofagitis (or thrush)
Varicella Zoster
Pneumocystis (PCP, PCJ)
CMV
Kaposis sarcoma HHV-8
Lymphoma
(HIV encephalopaty)
Cryptococcal meningitis
Toxoplasmosis
Case
 40 year old woman originally from Eritrea
seeks medical car at the ER because of
cough, fatigue and
 Temp 39, Sat 72% on RA. HR 100.
BP 110/70. Chest, sparse wheezing
otherwise clear bilaterally.
Case
CRP 46
Case
P.Jiroveci sputum, silver stain.
Goals for antiretroviral treatment
(ART)
 Suppress HIV replication
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Improve the immune defense to avoid opportunistic infections
Limit pathology associated with uncontrolled HIV replication
Limit the patients contagiousness
Prevent mother to child transmission
PEP (post exposure prophylaxis)
When to start treatment?
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Risk for opportunistic
infections
Risks associated with
untreated HIV infection
Risk of transmission (MTCT)
Other risk factors
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Risk of bad compliance and
resistance
Long term side effects
Drug interactions
Cost
When to start treatment?
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Risk for opportunistic
infections
Risks associated with
untreated HIV infection
Risk of transmission (MTCT)
Other risk factors
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Risk of bad compliance and
resistance
Long term side effects
Drug interactions
Cost
Treat everyone immediately !!
What to treat with?
Drugs
Reverse transcriptase inhibitors
 Nucleoside reverse transcriptase inhibitors
NRTI
 Non-nucleoside reverse transcriptase
inhibitors NNRTI
Mono-therapy vs combination therapy
 Should we use mono-therapy with AZT
(zidovudine, Retrovir) ?
Mono-therapy vs combination therapy
 Should we use mono-therapy with AZT
(zidovudine, Retrovir) ?
 Mono-therapy results in emergence of drug
resistant virus
Drug resistance
 HIV RT is “sloppy” creating approximately 3 x 10 -5
errors per nucleotide base per cycle of replication (i.e. 3
errors per copy)
 Replication is fast with estimated production of HIV virus
around 1 000 000 000 – 10 000 000 000 copies
produced /day
 This means that all possible mutations happen
statistically every day
How to avoid resistance
 Keep the virus replication low
 Have sufficient concentration of drug
 Use combination therapy to raise the genetic
barrier to resistance and to assist in lowering
the virus production
What do we use today?
NRTI
 Abacavir (ABC)
 Didanosine (ddI)
 Emtricitabine (FTC)
 Lamivudine (3TC)
 Stavudine (d4T)
 Tenofovir (TDF)
 Zidovudine (AZT)
NNRTI
 Delavirdine (DLV)
 Efavirenz (EFV)
 Etravirine (ETR)
 Nevirapine (NVP)
 Rilpivirine (RPV)
PI
 Atazanavir (ATV)
 Amprenavir (APV)
 Darunavir (DRV)
 Fosamprenavir (FPV)
 Indinavir (IDV)
 Lopinavir (LPV)
 Nelfinavir (NFV)
 Ritonavir (RTV)
 Saquinavir (SQV)
 Tipranavir (TPV)
Fusion Inhibitor
 Enfuvirtide (ENF)
CCR5 Antagonist
 Maraviroc (MVC)
Integrase Inhibitor
 Raltegravir (RAL)
 Dolutegravir (DTG)
 Elvitegravir (EVG)
What do we use initially
 1 NNRTI + 2 NRTI
Atripla (Efavirenz, Tenofovir, Emtricitabin)
What do we use initially
 1 INSTI + 2 NRTI
Tivicay+Truvada (Dolutegravir, Tenofovir, Emtricitabin)
What do we use initially
 1 PI + boost + 2 NRTI
Reyataz + Norvir + Kivexa/Truvada (Atazanavir, Ritonavir)
Kaletra + Kivexa/Truvada (Lopinavir, Ritonavir)
What happens when we treat?
What happens when we treat?
What happens when we treat?
What happens when we treat?
What happens when we treat?
What happens when we treat?
Post exposure prophylaxis (PEP)