HIV - 23, 25-7 Flashcards
What are the 3 types of transmission methods for STIs?
Direct sexual contact
Mother-to-child
Blood-to-blood
What are the risk factors for STIs?
Unprotected sexual activity Age Gender Ethnicity Sexual orientation Setting/sexual network
What are the complications of STIs? (x5)
Pre-term/low birth weight Congenital defects - syphilis Reproductive health Malignancies Interaction with HIV acquisition/transmission
What are the general STI prevention methods? (x6)
Condom use Prompt diagnosis + treatment Sexual abstinence Contact tracing + partner treatment Screen medical blood products No needle sharing
What is the epidemiology of STIs?
In LDCs, STIs + complications rank in top 5 disease categories for which adults seek health care
4% of deaths worldwide (6.6% in LICs) due to unsafe sex
What is a DALY?
Disability Adjusted Life Year
1 lost year of ‘healthy’ life
By summing all the DALYs across a population, you can measure the burden of disease
How is a DALY calculated?
DALY = YLL + YLD
Years Life Lost = no of deaths x life expectancy at age death occurred
Years Lost due to Disability
What is the incidence of gonorrhoea in England?
41 193 cases diagnosed in England (PHE, 2015)
What is the trend in gonorrhoea diagnoses in England + Wales over last 100 years?
Massive increase in 1918 + 1946 as troops return from World Wars
Decline in 1947-54 due to Abx + social stability
Increase in 1960s as sexual liberation; OCP; homosexuality decriminalised
Decrease from 1980s due to behaviour modification in response to PH campaigns for AIDs
Increase 74% 2005-10 due to diagnoses incidence
What is the relationship between infection and transmission in STDs?
Dynamic interplay among pathogen, subpopulation behaviour + prevention efforts
Infection + transmission are dynamic - risk depends on availability of Tx + behaviour
Phase appropriate prevention strategies + research issues important
What is R0?
Basic Reproductive number = average number of secondary cases generated by a single primary case in a fully susceptible population
What must R0 be in an epidemic/growth phase?
> 1
Each infected person must infect more than 1 person
How is R0 calculated?
Mean length of time infectious x rate at which sexual contact occurs x likelihood of transmission in a sexual partnership
TIME X RATE X LIKELIHOOD
What does the standard epidemiological model for STI in the population involve?
Core group/subpopulation who have a lot of partners that sustain transmission + persistence in wider population
Bridging population
General population
What are some examples of subpopulations who have higher rates of partner changes?
Young people
Urban
Sex workers
What is the definition of primary, secondary and tertiary prevention in STIs?
Primary = reduce risk of disease in UNAFFECTED people Secondary = reduce SEVERITY of disease in people with EARLY SIGNS Tertiary = Reduce IMPACT of disease in people with clinical condition
What is the definition of screening?
Process of identifying apparently healthy people who may be at an increased risk of disease
What are the components of control strategies for STIs?
Surveillance Early Dx Screening Effective Tx Contact tracing Population groups Monitoring + evaluation
What are the challenges to effective control interventions for STIs?
Undiagnosed/asymptomatic cases Resources for prevention/treatment Abx resistance Vaccination Partner notification Sexual behaviour change
What is the epidemiology of HIV?
HIV prevalence 36.9 million people living with HIV worldwide (WHO, 2018)
18 million on ART
35 million have died from HIV
Drastic decline of mortality since 2005
Incidence is decreasing but prevalence is increasing as better testing + Tx so more people living longer with HIV
Increased transmission in Africa as ARTs were rolled back
What are the problems with HIV medication?
Expensive Lifelong medication S/Es; toxicity Adherence Doesn't eradicate virus High levels of mutation Rapid development of resistance to monotherapy led to combination of drugs (HAART)
Who are the key populations in HIV epidemic settings?
Homosexuals
Healthcare workers
Sex workers
Transgender people
What are the barriers to HIV treatment?
Access Resources Belief Drug availability Health care facilities Stigma
What are the different types of biomedical interventions used for HIV? (X5)
GP41 inhibitors GP120 + CCR5 antagonists Reverse transcriptase inhibitors Integrase inhibitors Protease inhibitors
Describe the MOA of a GP41 inhibitor
Virion envelope covered in GP41 to bind with T helper cells
Prevent HIV from fusing with cell
Describe the MOA of a GP120 + CCR5 antagonist
Virion envelope covered in GP120 to bind to T helper cells
Prevent HIV from attaching to cell
Name + describe the MOA of a reverse transcriptase inhibitor
Prevents replication as retrovirus has RNA + virus uses reverse transcriptase to turn RNA into DNA which is then inserted into host DNA
Name + describe the MOA of an integrase inhibitor
Raltegravir
Prevent insertion into host genome
Describe MOA of a protease inhibitor
Prevent processing of HIV proteins which host cell machinery produces
What is the definition of efficacy?
The ability to produce a desired/intended result
What is the definition of effectiveness?
The degree to which something is successful in producing a desired result
What are the issues with the biomedical interventions for HIV?
Drug resistance High compliance required Need for 'simpler' regimens Management of long term toxicity Treatment NOT cure
What are the next steps of HIV treatment for the future?
Very early treatment e.g. HIV+ neonates Therapeutic vaccines Immune modulation Gene therapy Early ART (NEJM 2011 + 2016) - treatment as method of prevention + reduces risk of transmission by 96%
List the prevention strategies for HIV
Condoms (M+F) PEP (Post exposure) Prevention of vertical transmission Tx as prevention Male circumcision - Gray et al, 2012 found > 57% reduction Voluntary counselling + testing Clean injecting equipment PrEP (prophylactic)
Name 2 ART trials
PROUD trial (Lancet, 2016) IPERGAY trial (NEJM, 2015)
What are the issues of the current HIV biomedical interventions?
Hard to have trained staff
Lack of funding = lack of services
Gender based violence
Human rights - homosexuality is still illegal in some countries so by accessing care it is risky
What are the barriers to developing an effective biomedical prevention intervention?
Classic vaccines mimic natural immunity but no one has survived HIV
Most vaccines protect against disease NOT infection
Long latent period
Safety concern using live, attenuated pathogen
HIV has multiple mechanisms of immune evasion
High levels of mutation
Absence of neutralising antibodies
Destruction of immune response
How will progress of finding a HIV vaccine be accelerated?
Better understanding of antigenicity vs immunogenicity
Better understanding of how broadly neutralising antibodies evolve in HIV infections
Methods to stabilize the native Env trimer, to immunize as well as elucidate the crystal structure
What did the Thai trial (RV144),2006 show?
Protection from infection is possible
Protective efficacy around 31%
Highest protection in first 6-12 months
What are the prospects for HIV cure?
Requires elimination of all free HIV particles + all infected cells
Latently-infected cells persists for years + HIV starts replicating again immediately when therapy is stopped
Would take 70 years to eliminate all virus + infected cells w/ current therapy
New goal is to identify new strategies to eliminate latent infection
What are the strategies to eliminate the HIV reservoir?
‘Flush out’ virus by activating latently infected cells and killing them (kick + kill)
Immunologic Tx targeted at reservoir
Gene therapy (CCR5 modification/elimination)
CCR5 delta32 stem-cell transplants
What is the continuum of care in HIV?
Testing
Enrol + retain in care - loss to follow up
Early retention in care - stop taking drug in early stages of ART
Lifelong retention in care - non-adherence to ART
What are the issues with the HIV continuum of care?
Identification - if not diagnosed, no ART to suppress viraemia
Evidence shows that having the diagnosis makes you less likely to engage in high risk sexual behaviour, even if not seeking treatment
Retention - viral resistance develops + inadequate suppression of viraemia if inadequate retention
When is a HIV patient most infectious?
Primary infectious period = first 3 months
Highest viral load
Generic flu-like symptoms, abdo pain, rash
VERY FEW PEOPLE PRESENT at this stage when most ideal to treat
AIDS-defining illness at the end also has high viral load but this is too late as they are probably too old to be very sexually active
What is the relevance of behavioural + structural interventions for success of biomedical prevention interventions?
Hand in hand
In UK, MSM are most affected group but globally, sex workers are
Name 3 behavioural interventions for HIV
Encourage regular testing for HIV - Universal testing, regular sub-population testing at intervals
Encourage health seeking behaviour - sexual health education, health training
Increase adherence to biomedical prevention interventions (non-ART) - youth condom promoters, peer support, counselling, motivational interviewing
Name 3 structural HIV interventions
Decriminalisation of sex work, IVDU, homosexuality, needle exchange
Reduced inequality - business start-up grants, CCT, Single-sex/joint group meetings
Increased access to health services - universal health coverage plan
What was found in S Africa with regards to age-specific gender disparity?
HIV prevalence increases with age from teens and more rapidly for women > men
Young women have sex with older men as they have more power and money
School attendance significantly reduced risk of HIV acquisition
What are the 5 key barriers to ART increase in resource-limited settings
Access to medicines - affordability
Funding
Simplification - public health approach needed due to lack of doctors + labs in LICs –> task shifting + decentralisation; also drug regime is too complicated, pushing for once daily pill
Models of delivery - access in primary care clinics in rural areas where hospitals are far away
What is AIDs exceptionalism?
HIV is unique in that there are billions of dollars of funding AND specific programmes that exist specifically for reducing the burden of HIV
What is the only UN programme for one disease?
UNAIDS (1996) has 90 90 90 by 2030
90% tested
90% treated w/ ART
90% suppressed virologically
Is the testing target of UNAIDs 90 90 90 being achieved?
No country is reaching 90% target
Globally < 60% know their status
Large variability - men’s testing is getting neglected especially in countries where being gay is illegal
What are the enablers for testing for HIV?
Lay testing
Community testing - especially partner testing
Self-testing - will people actually seek care if positive?
Is the treatment target of UNAIDs 90 90 90 being achieved?
People present late to care
High rates of lost to care pre-ART
IeDEA-WHO Collaboration, 2015 found > 15% lost within 12 months in 55 countries
Long delays in starting ART
What are the enablers of treatment for HIV?
Earlier testing + improved linkage
Accelerated ART initiation (WHO, 2017 recommended to start ART same day as diagnosis)
Advanced disease package - enhanced prophylaxis in advanced disease
Treat all
What are the problems with the suppression part of UNAIDS 90 90 90?
High rates of loss to follow up - treatment fatigue
Sub-optimal adherence - forgetting, travel + migration, change to routine, distance to clinic, stock-outs
Differentiated service delivery - timing, location + mode of delivery depend on context
