46
Clinical features of Tuberculosis, Hepatitis C and HIV Mas Chaponda Consultant Infectious Diseases Liverpool University Hospitals
Clinical features of Tuberculosis,
Hepatitis C and HIV
Mas Chaponda
Consultant Infectious Diseases
Liverpool University Hospitals
Aims of today
• Understand Epidemiology
• Presentation
• Testing
• Treatment
• Prevention
Case 1
• 62yo Man
• Weightloss
• Headache 4 months
• Progressive confusion
• Falls
2 billion latent infections
26% of avoidable adult deaths in
developing world
1.7 million
deaths /yr
9.4 million new cases/yr
Epidemiology & Pathogenesis of TB
Map Illustrating High Burden Countries
Inhalation of TB
Post-Primary Pulmonary TB
Disseminated Disease
Latent TB
Clearance
Diagnosis of active TB
Reactivation
10% lifetime risk in HIV negative10-20% annual risk in HIV positive
Primary Pulmonary TB
TB Infection vs Disease
Clinical Signs
• Cough
• Fever,
• Night sweats,
• Weight loss
• Lymphadenopathy
• Chest signs
• Haemoptysis
Pleural TB
•Pleural aspiration
•Serous, exudative, lymphocytic fluid
•Pleural biopsy by experienced operator
•Video-assisted thoracoscopy
Pericardial TB
• Often in disseminated disease
• Present with dyspnoea
• Beck’s triad ( hypotension, raised JVP and quiet heart sounds ) signifies tamponade
Meningeal TB
• Basal inflammatory arachnoiditis• Vasculitis, • CN and spinal root compression• Hydrocephalus• Tuberculomas
• Insidious onset- weeks• Altered conciousness• CN palsies• High morbidity and mortality (35%)
Ziehl-Neelsen Stain
Advantages
• Cheap
• Rapid
Disadvantages
• Insensitive (10 000 bacilli/ml sputum)
• Labour-intensive
Treatment of active drug-sensitive TB
• DAILY administration of standard TB
therapy in patients with drug-sensitive TB
• 2RHZE/4RH
• CNS TB: 2RHZE(+steroids)/7-10RH
• Fixed-dose combination tablets
*Vernon et al, Lancet 1999; Burman et al, J Respir Crit Care Med 2006; Narendran et
al, CID 2014; Gopalan et at, JAMA Intern Med 2018;
BCG vaccination• High variability of protective effect across studies
• Overall protective efficacy about 50%
• Mainly prevents severe disseminated disease in young children
(TB meningitis, miliary TB)
• Effects in HIV infected children unclear, not recommended
Case 2
• 32yo MSM
• Bipolar
• Alcohol excess
• Slamming parties
• Abnormal LFTs
The HCV virus• HCV is an blood-borne RNA
virus that infects the liver
cells
• 7 types of HCV (=genotypes, GT7 discovered recently) with multiple subtypes (a, b, c)
• Varying rates of progression & different response totreatment
Prevalence of hepatitis C is rising:
laboratory reports* in England (1992–2011)
*Statutory notification by diagnostic laboratories was introduced in October 2010
Hepatitis C in the UK: 2012 Reporthttp://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/Hepatiti
sC/
Nu
mb
er
of
rep
ort
s
12,000
10,000
8,000
6,000
4,000
2,000
01992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Year
In the beginning….partying “occasionally”
Social site and apps have made
finding Chem-Sex easy and
anonymous
IDU or ‘slamming’ has become
more common place
Natural history of HCV infection
HIV and
Alcohol
Adapted from Mauss, S. et. al., editors. Hepatology: A clinical textbook: Flying Publisher; 2010.
HCV is an asymptomatic slowly progressive
disease evolving over 10 to 20 years
Assessment of Disease
HCV: 7.2KPA (< 7KPa,F2>9.5, F3>12.5, F4 >14)
1. Friedrich-Rust et al. Gastroenterology 2008;134:960-974.
Median of 10 readings:
>60% success rate
IQR:median < 30%
• Hep C ab
• Hep C PCR
• Hep C genotype
• LFTs
• Abdominal USS
• Fibroscan
1. McHutchison JG, et al. N Engl J Med 1998;339:1485–92; 2. Fried M, et al. N Engl J Med 2002;347:975–82
3. Manns MP, et al. Lancet 2001;358:958–65; 4. Hadziyannis SJ, et al. Ann Intern Med 2004;140:346–55
5. Jacobson IM, et al. Hepatology 2010;52(Suppl):427A; 6. Sherman KE, et al. Hepatology 2010;52(Suppl.):401A
7. Poordad F, et al. Hepatology 2010;52(Suppl.):402A; 8. Foster GR, et al. Hepatol Int 2011;5(Suppl.1):14
100
80
60
40
20
0
SV
R r
ate
(%
)
1990 2000 2010
2–7%
IFN1
16–28%
IFN
+
RBV1
42–54%
Peg-IFN
+
RBV2–4
59–75%
DAA
+
Peg-
IFN +
RBV5–8
Evolution of chronic HCV genotype 1 treatment
Evolution of Hep C Treatments
Dieterich D et al. CROI 2014, P#24; Rodriguez-Torres M et al. IDWeek 2013; P#714; Sulkowski M et al. Lancet Infect Dis 2013;13:597–605; Sulkowski M et al. Ann Intern Med 2013;159:86–96; Sulkowski M et al Lancet 2014;314:653–61; Sulkowski M et al. AIDS 2014; P#104 LB; Torriani FJ, et al. N Engl J Med 2004;351:438–50; Rockstroh JK, et al. AASLD 2014. Boston, MA, Abstract 195. AASLD AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed February 2016; Rockstroh J, et al. Lancet HIV 2015 Published Online; Wyles, D. et al, EASL 2016, PS104
SV
R R
ate
(%
)
2015 AASLD/IDSA Guidance: “HIV/HCV-coinfected persons should be treated and retreated the same as
persons without HIV infection, after recognizing and managing interactions with antiretroviral
medications”
‡
Efficacy rates are not directly comparable, due to differing study designs
GZR/EBR 12 wksC-EDGE
SOF/VEL12 wksASTRAL-5
1986 2011 2014Years are not to scale
2004
IFN+RBV24 wks
PEG48 wks
PEG+RBV48 wks
BOC+PEG+RBV24-48 wks
TVR+PEG+RBV24-48 wks
SMV+PEG+RBV24-48 wks
SOF+PEG+RBV12 wksStudy 1910
SOF+RBV24 wksPHOTON-1, PHOTON-2
LDV/SOF12 wksION-4, ERADICATE
OMV/PTV/RTV+DSV+RBV12-24 wksTURQUOISE-1
2013 2016
Where are we NOW!
Ledipasvir+
Sofosbuvir
(Harvoni)
2019
Agents
Sofosbuvir +
Velpatasvir
(Epclusa)
Grazoprevir +
Elbasvir (Zepatier)
Glecaprevir
/Pibrentasvir
Case 3
▪ 35yo Woman
▪ Headache 4 months
▪ Progressive confusion
▪ Psychotic
Psychiatry review
▪ Experiencing visual hallucinatory experiences / more like illusions as she knows that seeing her dressing gown move is due to her delirium / confusion.
▪ She has also seen figures in her room and has been quite disturbed by these experiences - she has responded, to a degree, from Haloperidol ..
No persecutory delusions or auditory hallucinations.
▪ No grandiosity / expansive mood but I understand that she was quite aroused recently / more acutely confused.
▪ Impression, 1 hyperactive delirium, appears to be due to infection?
27
• PLHIV exhibited poorer cognitive function and higher rates of cognitive impairment compared with people
in the HIV-negative group
UK POPPY study: Cognitive function in PLHIV
▪ Boxplots of demographically adjusted cognitive domain T-scores by HIV-1 serostatus
POPPY, pharmacokinetic and clinical observations in people aged over 50 years.
Underwood J et al. EACS 2015. #PE15/9.
2
8
290 PLHIV and 97 demographically comparable HIV-negative controls aged >50 years
80
60
40
20
0 Attention/
working
memory
Co
gn
itiv
e d
om
ain
T-s
co
re
Executive
function
Processing
speedVisual
attention
Verbal
learning/
memory
Visual
learning/
memory
Global
score
p<0.01p=0.83p=0.14 p=0.03 p<0.0001 p=0.06 p<0.0001
HIV-status:
PLHIV
HIV-negative subjects
It is generally acknowledged that HIV is a descendant of SIV(Simian ImmunodefiencyVirus),and crossed the species barrier some time ago. Like HIV-1 infection in humans, SIV infection in rhesus macaques is pathogenic. However, in some species, such as sooty mangabeys, it is not. This may give insight into how some people are able to tolerate their HIV infection.
Modes of HIV/AIDS Transmission
The Global Challenge
North America
2,000,000 infected
Caribbean
440,000 infected
South America
1,500,000 infected
Sub-Saharan Africa
22,000,000 infected
North Africa & Middle East
380,000 infected
Western Europe
570,000 infectedEastern Europe / Central Asia
1,200,000 infected
East Asia & Pacific
1,200,000 infected
South-East Asia
4,000,000 infected
Australia &
New Zealand
74,000 infected
World AIDS Facts
Estimated number of people living with HIVFigure 3: Estimated* number of people living with HIV (diagnosed and undiagnosed) in the UK, using the MPES model, 2016
• PHE estimated that there were 89,400 people living with HIV in the UK in 2016• Of these 78,900 had been diagnosed, leaving 10,400 undiagnosed cases
Source: PHE Towards elimination of HIV transmission, AIDS and HIV-related deaths in the UK report, 2017
33
Diagnosed HIV prevalence (per 1,000 population aged 15 - 59
years): England, 2016
34
Number of men/boys and women/girls newly diagnosed with
HIV: United Kingdom, 2007 - 2016
35
New HIV diagnosis by place of birth: United Kingdom, 2007 -
2016
Excludes people with missing country of birth information
HIV-related illness is CD4
dependent
CD4+
(cells/µL)
800-
600-
400-
200-
50-
0 2 4 6 8 10
Seroconversion:
Primary HIV
CMV
MAI
Pneumococcal pneumonia
Candida vaginitis
TB
Years after infection
Oral Candida-infection
Kaposi sarcoma
Lymphoma
Dementia
Oral haircell-leukoplacia
Cachexia
Toxoplasmosis
TB
PCP
HSV
Candida esophagitis
Cryptococcosis
kaposi sarcoma
Oral lesions
Oral candidiasis Oral hairy leukoplakia
Risk factors for developing HIV-related neurocognitive disorders
*Non-HIV-related risk factors.
CSF, cerebrospinal fluid; CVA, cerebral vascular accident; OI, opportunistic infection.
1. Cross S et al. J Neuroimmune Pharmacol 2013;8:1114–22; 2. Attonito JM et al. Front Public Health 2014;2:105; 3. Ellis R and Letendre SL. Neurotherapeutics 2016;13:471–6; 4. Anand P et al. AIDS Behav 2010;14:1213–26.
CD4 nadir*1
Duration of
HIV
infection*2
CNS toxicity
of ART*4
CNS
penetration
of ART*3
CNS OI*3 HCV1,4
HIV CSF
escape*3
Mental
health1,4
Head trauma4
Other
dementias4
Alcohol &
recreational
drugs2,4
Race1
Education1
3
9
HIV testing – the truth
20-minute pre-test counselling? NOHealth advisor to speak to patient? NOTake sexual history? NOSpecialist HIV counselling skills? NO
Recommend as a routine test
▪ Only verbal discussion required
▪ Doctors and nurses should encourage patients to take up HIV tests in the same way they promote any other tests
Simplified regimes
HIV transmission #U=U
HIV Prevention England. It Starts With Me Campaign April 2017
Efficacy of HIV prevention strategies from RCT
Karim SS et al. Lancet. 2011 [
1000 20 40 60 80
Efficacy (%)
Study Effect size, % (95% CI)
ART for prevention; HPTN 052, Africa, Asia, Americas
96 (73–99)
PrEP for discordant couples;Partners PrEP, Uganda, Kenya
73 (49–85)
PrEP for heterosexual men and women; TDF2, Botswana
63 (21–84)
Medical male circumcision; Orange Farm, Rakai, Kisumu
54 (38–66)
PrEP for MSMs; iPrEX, Americas, Thailand, South Africa
44 (15–63)
Sexually transmitted diseases treatment; Mwanza, Tanzania
42 (21–58)
Microbicide;CAPRISA 004, South Africa
39 (6–60)
HIV vaccine;RV144, Thailand
31 (1–51)
Thank you for your attention
