HIV Flashcards
what is the sensitivity of HIV screening tests?
high sensitivity (>98%)
What do HIV screening tests usually detect?
- antibodies to HIV-1 and HIV-2
4th gen - also detects - HIV-1 p24 antigen
Seological tests for HIV are usually based on what laboratory assay?
Serological tests - usually use
enzyme immuno assays (EIA)
4th generation (antibody and antigen) tests - more sensitive than antibody only tests
Why are 4th generation HIV tests recommended?
4th generation = antibody and antigen tests,
More sensitive than antibody only tests
Better in detecting or excluding HIV when a recent exposure has occurred (<4-6 weeks).
In what situation may there be a false negative HIV test?
A test can be falsely negative very early in the window period
e.g. If a high risk HIV exposure occurred in the previous 4-6 weeks s
A negative test with a 4th generation (antigen + antibody test) EIA at 4 weeks excludes HIV infection with a high degree of certainty.
(a few cases described of prolonged seroconversion, usually with simultaneous other viral illness)
What confirmation is required of a positive HIV screening test?
Confirmation by second and third serological test
what is an equivocal or indeterminate HIV test?
An equivocal / indeterminate tests = a positive screening test which is negative when tested by a second and third serological test.
Causes of an equivocal or indeterminate HIV test
Usually caused by a false positive reaction
Could be an early seroconversion when the screening test is more sensitive than the confirmatory tests.
Management of an equivocal or indeterminate HIV test
Repeat the sample 1 wk later
Will identify seroconversion if the confirmation test(s) become positive and/or p24Ag or HIV viral load is detectable
Patient can be reassured of false positive reaction if the repeat blood, drawn at least 1 week later, is negative
What test can be used for HIV incidence testing
Antibody avidity testing
Can predict whether the infection occurred in the preceding 4-5 months.
(sensitivity + specificity of 96% and 97%)
What principle foes HIV Antibody avidity testing utilise?
The test exploits the principle that the initial antibodies bind less strongly (low avidity) to antigen compared to antibodies produced later as part of the evolving immune response.
Can predict whether the infection occurred in the preceding 4-5 months.
When can HIV seroconversion be diagnosed?
Seroconversion can be diagnosed when the 4th generation screening test is positive but a confirmatory (3rd generation) test is negative.
A p24Ag or viral load test needs to be positive.
Evolving line blot assays with additional bands developing on follow-up sampling can also be used.
Sensitivity of HIV tests?
HIV tests - incredibly sensitive
>98%
due to the high levels of HIV antibodies produced by an infected person
Specificity of HIV tests?
specificity >98%
When might salivary HIV diagnostic tests be useful?
for children / severe needle phobia
what is the correct storage of HIV samples
No refrigeration of samples is necessary unless stored for more than 1-2 days.
What proportion of new HIV diagnoses are MSM?
UK in 2015
MSM = 46% of new HIV diagnoses
What is a late HIV diagnosis?
For public health monitoring - late HIV diagnosis = CD4 cell count <350 within 3m of HIV diagnosis
Very late HIV diagnosis = CD4 count <200.
What is the significance of a late HIV diagnosis?
People diagnosed late are at increased risk of developing an AIDS-defining illness
+ have 10x increased risk of death in the year following their diagnosis
HIV prevention strategies
Condom use
PEPSE
Serosorting/stategic positioning - mixed data
PREP
Male circumcision - data from Africa suggests MC protects heterosexual men from acquiring HIV
Reduce the number of partners
What is the approximate rate of STS and HIV co-infection
Syphilis-HIV coinfection remains high
Up to 40% of cases of syphilis being in HIV infected MSM
How may being HIV +ve affect the presentation of STS
some minor differences syphiis presentation in HIV +ve patients include:
- primary syphilis- up to 70% present with >1 chancre + larger / deeper lesions
- 25% present with concomitant lesions of primary and secondary stages at presentation
- atypical and severe presentations of syphilis occur more frequently (still a v small minority)
- Syphilis can cause transient increase in the viral load and decrease in the CD4 cell count - resolve after treatment
Differences in managing STS in HIV +ve patients
- HIV patients are more likely to present with neurological syphilis in early syphilis
- HIV infection associated with increased risk of neurological complications in the short and long term
- consider treating all HIV patients with a neurosyphilis drug regimens given the high rates of positive CSF
Globally what proportion of people living with HIV are women?
Women >15 years = approximately 50% of global adults living with HIV
- The burden of disease in women is not evenly distributed worldwide
In the UK what proportion of people living with HIV are women?
In the UK in 2015 31% of patients accessing HIV care were women
What is the primary aim of ART?
To prevent mortality and morbidity associated with chronic HIV infection
Effective
Tolerable
Low drug toxicity
Improve physical + psychological well-being
Reduce onward transmission - sexual, MTCT
What proportion of patients on ART achieve a suppressed HIV VL?
93% (2013 data)
Before prescribing ART what topics should be discussed with the patient to assess their readiness to take therapy?
Understanding of HIV therapy
Perceptions of personal need for ART
Concerns about ART / specific ARV drugs,
Concerns re social consequences (disclosure/ lifestyle interference)
Confidence re adherence
Psychological issues / concerns
Socio-economic factors (incl. poverty, housing, immigration status, domestic violence)
Pregnancy or parenting plans
Factors affecting adherence to ARVs
adverse effects
Social beliefs
Cultural beliefs.
Depression sig. associated with low adherence [1
Anxiety
Problematic drug or alcohol use
Socio-economic status - poverty, non-employment, unsettled immigration status, lack of supportive network
when should ARVs be started for a patient presenting with an AIDS defining illness?
Individuals presenting with an AIDS-defining infection
Or a serious bacterial infection and a CD4 count <200
Start ART within 2 weeks of initiation of specific antimicrobial chemotherapy
when should ARVs be started for a HIV diagnosis
At time of diagnosis
What was the ACTG 5164 study
and what did it show?
ACTG 5164 study
demonstrated fewer AIDS progressions/deaths
And improved cost-effectiveness
when ART was commenced within 14 days treatment for acute infection (e.g. PCP)
Rather than ART initiation at the completion of antibiotic treatment
definition of Primary HIV infection (PHI)
Primary HIV infection (PHI) = HIV infection within a maximum of 6 months from the estimated time of HIV transmission.
Diagnosed based on laboratory test results
Which studies showed clinical benefit to starting immediate ART over deferral
START, TEMPRANO and HPTN 052 trials
What factors would encourage prioritisation of early ART initiation
primary HIV infection
low initial CD4 T cell counts <350
high plasma viral loads (>100,000 copies HIV RNA)
short test intervals - diagnosis within 12 weeks of a previous negative test
Neurological involvement
Any AIDS-defining illness
What was the SMART study
and what did it show?
The SMART study compared 2 ART strategies in HIV-infected adults with CD4 counts > 350
1st group = viral suppression strategy = continuous ART to maximally suppress HIV replication.
2nd group = CD4 count-guided ART interruption strategy (drug conservation) = involved stopping ART when CD4 counts >350 and re-initiating ART when CD4 <250
treatment interruption = increased all-cause mortality
seen regardless of the lowest point of CD4 cell count.
Potential downsides to starting ART in primary HIV infection
Ambivalence to ART at a time of emotional challenges - an risk poor adherence and the development of drug resistance
Patient may be in a vulnerable psychological state and ll-prepared to commit to starting long-term treatment.
Potential benefits to starting ART in primary HIV infection
Better probability of immunological recovery to normal levels
Patient may be comforted to know they are taking immediate control of their infection
Reduced risk of onward transmission at a time of v high VL
Reduction in morbidity
Clinical benefit from starting ART irrespective of CD4 count (START, TEMPRANO and HPTN052 trials)
Limitation of viral reservoir
Advice for reduction in transmission of HIV
Initiation of ARVs will reduce the risk of onward sexual transmission - discuss as a part of safer sex messages
Undetectable VL for 6m + means it isn’t possible transmit HIV (U=U)
Condoms
Water based lubricant
Avoid sharing needles and injecting equipment
Pre-exposure prophylaxis (PrEP)
Post-exposure prophylaxis (PEPSE)
Antenatal screening
How soon after initiating ART does the VL become undetectable?
Taking ART does not result in immediate viral suppression.
Most achieve viral suppression by 3–6 months
Integrase inhibitors are characterised by more rapid viral suppression - most undetectable by 1–3 months
What is the PARTNER study
and what did it show?
PARTNER study demonstrated a protective effect of viral suppression in serodifferent couples
HIV-positive person on suppressive ART - VL <200
condomless sex acts - 16,800 in MSM and 28,000 in heterosexual couples
no cases of HIV transmission
86 would have been expected based on previous incidence studies
Advice for sero-discordant heterosexual people wishing to conceive
If fully suppressed on ART with undetectable VL for 6m+
U=U
Sex without condom around time of ovulation = timed UPSI = very little to no risk
PrEP does not add any benefit but may carry SE - not advised in current guidelines
Sperm washing not recommended in the context of viral suppression
What ART is recommended to start for new diagnoses of HIV
therapy-naïve patients with HIV
recommend starting ART with 2 nucleoside reverse transcriptase inhibitors (NRTIs) as the backbone
plus 1 of: ritonavir-boosted protease inhibitor (PI/r), non- nucleoside reverse transcriptase inhibitor (NNRTI) or integrase inhibitor (INI)
e.g. Truvada (Tenofovir-DF and emtricitabine) and Raltegravir
What drugs are in Truvada
Tenofovir-DF and emtricitabine
What drugs are in Kivexa
Abacavir and lamivudine
What test is required prior to starting a patient on Abacavir
HLA-B * 57:01
What is the HLA-B * 57:01 test done for?
To determine if a patient is likely to have a hypersensitivity reaction to Abacavir
What are critical outcomes to consider when choosing which ART to start?
Viral suppression at week 48/96, proportion with virological failure, proportion developing resistance, proportion discontinuing for adverse events, proportion with grade 3/4 adverse events
In which patients must Abacavir not be used
HLA-B * 57:01 positive
What is the main risk associated with abacavir
abacavir and cardiovascular disease
Abacavir is not to be used in individuals at high risk of CVD
What is the main risk associated with tenofovir-DF
Renal toxicity
tenofovir-DF is not used in people with stage 3–5 CKD or at high risk of progression of CKD
Why is tenofovir-AF different to tenofovir-DF
Tenofovir alefenamide = new formulation of tenofovir
Significantly lower plasma concentrations of tenofovir
Hypothesis = lower plasma concentrations
should = less negative impact on renal and bone markers
More potential drug interactions for tenofovir-AF that do not apply to tenofovir-DF
Which nucleoside reverse transcriptase inhibitor backbone is commonly used for starting ARVs in treatment naive HIV patients?
Tenofovir-DF and emtricitabine
or
Tenofovir-AF and emtricitabine
Alternative - Abacavir and lamivudine
Which third agent is commonly used for starting ARVs in treatment naive HIV patients?
start combination ART containing one of atazanavir/r, darunavir/r, dolutegravir, elvitegravir/c, raltegravir rilpivirine
or efavirenz is an acceptable alternative third agent
Main adverse events from efavirenz-based regimens
Potential for significant CNS toxicity
Higher risk of suicidality
what is Cobicistat
Cobicistat is an inhibitor of CYP3A isozymes
Used as a pharmacokinetic booster of other antiretroviral drugs
Alternative to ritonavir- boosted PI
What is the current evidence regarding PI monotherapy for initial HIV treatment
Data limited
Associated with lower rates of virological suppression at 48 weeks
Emergence of PI mutations
No significant differences in tolerability
NOT recommended
What is the risk of low adherence to ART for HIV treatment
Associated with:
- drug resistance
- risk of disease progression
- risk of progression to AIDS
- death
- increased risk of HIV transmission to others
- increased costs of treatment
What factors may cause non-adherence
Both intentional and unintentional causes
Unintentional non-adherence is linked to limitations in capacity or resources that reduce the ability to adhere to treatment as intended.
Intentional non-adherence is a result of a decision informed by beliefs, emotions or preferences
Benefits of using single tablet regimens for HIV treatment
Improved adherence
Reduced selective adherence
Patient preference
Improvement in quality of life
What drug interactions should be considered when dispensing ARVs
methadone contraceptives anti-epileptics antidepressants lipid-lowering agents acid-reducing agents certain antimicrobials (e.g. clarithromycin, minocycline and fluconazole) some anti-arrhythmics TB therapy anti-cancer drugs immunosuppressants phosphodiesterase inhibitors anti-hepatitis C virus therapy
For what reasons may ART need to be interrupted?
Once ART has been started it should be continued.
frequent interruptions or interruptions >1-2 days should only be considered in exceptional circumstances.
e. g.
- Severe drug toxicity (e.g. hepatotoxicity).
- Severe psychological distress.
How long of an interruption in ART use is usually ok
An interruption of 1–2 days can usually be managed
Unlikely to be associated with adverse outcomes
Causes of virological failure on ART
Partial HIV drug resistance Extensive resistance X4 tropic virus Poor adherence Unsuccessful retention in care Sporadic detectable HIV RNA “blips” intolerance to the current regimen pharmacokinetics drug interactions
What is the virological failure rate on first-line NNRTI-based regimens in the UK
18%
Approximately 4% fail in the first year
Definition of virological suppression
Achieving and maintaining a VL level <50 copies/mL.
Definition of virological failure
Virological failure = incomplete virological response after commencing treatment or evidence of confirmed virological rebound to >200 copies/mL.
Definition of incomplete virological response
Incomplete virological response = 2 consecutive VL >200 after 24 weeks
without ever achieving VL <50
Definition of virological rebound
Virological rebound = failure to maintain a VL <50 on two or more consecutive occasions
Definition of Low-level viraemia
Low-level viraemia = a persistent VL between 50–200
Definition of a Virological blip
Virological blip = after virological suppression, a single VL between 50 and 200 copies/mL followed by an
undetectable result
Management of a virological blip
Virological blip = A single VL 50–200 copies/mL preceded and followed by an undetectable VL
Usually not a clinical concern
- clinical vigilance
- adherence reinforcement
- check for possible interactions
- repeat testing within 2–6 weeks depending on ARV regimen
Management of a virological blip where a single VL is >200
investigate
rapid re-test
+/- genotypic resistance test
May be indicative of virological failure
Management of HIV and TB co-infection
All patients with HIV TB co-infection should start ART
If CD4 count <50 start ART as soon as TB treatment is
tolerated - wherever possible within 2 weeks
If CD4 count ≥50 defer ART until 8 - 12 weeks of TB treatment. - esp if difficulties with drug interactions / adherence / toxicities
Which ART combination is recommend first-line in TB/HIV co-infection
Tenofovir-DF + emtricitabine (Truvada)
+ Efavirenz
When do you start ARVs for HIV and HBV coinfection when HBV requires treatment
Start ART promptly
Include tenofovir-DF and emtricitabine
or tenofovir-AF and emtricitabine
When do you start ARVs for HIV and HBV coinfection when HBV does not require treatment
Start ART - not as urgent
Include tenofovir-DF and emtricitabine
or tenofovir-AF and emtricitabine
When do you start ARVs for HIV and HCV coinfection when HCV treatment is to start start immediately
Start ART before HCV treatment commenced
Acceptable to defer if CD4 cell count >500 cells/μL - discuss viral hepatitis specialist
Which ARVs have good antiviral activity against both HIV and HBV.
Tenofovir-DF
tenofovir-AF
emtricitabine
lamivudine
Impact of HIV confection on HCV infection
HIV impacts HCV infection.
- higher HCV viral loads,
- faster rates of fibrosis progression
- increased risk of cirrhosis
- more frequent development of end-stage liver disease / hepatocellular carcinoma / liver-related death
- The efficacy of pegylated interferon (PEG-IFN) lessens as the CD4 cell count declines
When to start ART in patients with AIDS-defining malignancies = Kaposi sarcoma, high-grade B-cell non-Hodgkin lymphoma and invasive cervical cancer a
Commence ART promptly regardless of CD4 cell count or HIV viral load
Kaposi sarcoma
High-grade B-cell non-Hodgkin lymphoma
Invasive cervical cancer
When should we start ARVs in patients with HIV-associated nephropathy
start ART immediately irrespective of CD4 cell count
When should we start ARVs in patients with end-stage kidney disease who are suitable candidates for renal transplantation
start ART immediately
Effect of starting ARVs in patients with HIV-associated nephropathy
HIV-associated nephropathy - typically encountered in black individuals with advanced immunodeficiency and detectable HIV RNA levels
ART = renal histological improvement, trend towards delayed progression to end-stage kidney disease
Which ARVs are associated with reductions in eGFR
tenofovir-DF
atazanavir
lopinavir
Which ARVs are recommended for patients with CVD risk factors
individuals with a high CVD risk:
First-line ARV therapy = tenofovir-DF + emtricitabine
or lamivudine and dolutegravir
or raltegravir
or rilpivirine
What is the START study?
What did it show?
study of 4685 adults with CD4 >500 in 35 countries
Randomised to start ARV immediately or delayed until CD4 <350
Reduced adverse events by 57% at 3 years in immediate group (relative risk)
ARR = 2.3%
Similar between high and low income countries
Define primary HIV infection
HIV within 6 months of transmission
In primary HIV infection when should ART initiation be prioritised
All patients should be offered immediate ART.
Prioritise primary HIV if
- low CD4
- high VL (>100,000)
- short test interval (e.g within 12 weeks of prev negative test)
Which ARV is the only ARV with a licence for use during pregnancy?
zidovudine
What proportion of HIV +ve pregnant women are diagnosed before the current pregnancy?
80%
of whom 60% were already on ART at conception
Which ARV should be avoided in patents with current or past mental health issues
Avoid efavirenz
If a current or past history of depression, psychosis, suicidal ideation, attempted suicide, risk of self-harm
Impact of HIV on BMD
HIV-1-positive individuals have lower BMD at the femoral neck, hip and lumbar spine
HIV is an independent risk factor for low BMD
What impact does initiation of ART have on BMD
Initiation of ART is associated with a reduction in BMD of 2–6%
bone loss is generally restricted to the first year with a relatively stable pattern thereafter
Intermittent use of ART is associated with reduced bone loss during follow up
For women conceiving on cART what is the minimum number of CD4 cell tests taken during pregnancy
women conceiving on cART
Minimum of 1 CD4 cell count at baseline
and one at delivery
Recommended ARV combination in pregnancy
Abacavir / lamivudine OR Tenofovir DF / emtricitabine AND Efavirenz OR Atazanavir/r
For women diagnosed with HIV in pregnancy when should ARVs be started
Start cART as soon as possible if baseline viral load >100,000
Or at the start of the second trimester if baseline viral load 30,000 - 100,000
Or as soon as able to in second trimester where the baseline viral load ≤30,000
All women should have commenced cART by week 24 of pregnancy
What impact may hyperemesis have on timing of starting ARV for newly diagnosed HIV in pregnancy
May need to defer treatment to the start of the second trimester if the woman is experiencing nausea and/or vomiting of pregnancy
What is the timeframe for the cut off of a ‘late-presentation’ of HIV in pregnancy
HIV diagnosed or HIV +ve patient presenting at 28/40 + = late presentation
Should commence cART without delay.
What is the deciding factor for whether a HIV +ve pregnant patient can have a vaginal birth
vaginal delivery is possible if the woman commences cART and achieves a viral load of <50 HIV RNA copies/mL by 36 weeks
Management of an untreated HIV +ve woman presenting in labour at term
STAT dose of nevirapine 200 mg
and commence oral zidovudine 300 mg and lamivudine 150 mg bd;
and raltegravir 400 mg bd;
and IV zidovudine for the duration of labour - until cord clamped
And high risk neonatal management by paediatric team
If delivery is not imminent, a CS should be considered.
Why is a STAT dose of nevirapine advised for untreated HIV +ve women presenting in labour at term
Nevirapine rapidly crosses the placenta
achieves effective concentrations within 2 hours
and maintains concentrations in the neonate for up to 10 days
Management if a woman’s HIV status is unknown during labour
a point-of-care test (POCT)
If test is positive (reactive) perform a confirmatory test Start treatment to prevent vertical transmission immediately
Baseline samples for CD4 cell count, viral load and resistance should be collected. T
Three-drug PEP should be given to the neonate
Can HIV positive pregnant women have invasive diagnostic tests if required?
e.g. Amniocentesis
Deferr until HIV viral load suppressed to <50 HIV RNA copies/mL
If not on cART and the invasive procedure cannot be delayed until viral suppression is achieved - recommended to start cART to include raltegravir and give a STAT dose nevirapine 2–4 hours prior to the procedure
Can HIV positive pregnant women have an ECV if required?
Yes
if plasma viral load <50 HIV RNA copies/mL.
Mode of delivery for pregnant HIV +ve women with plasma viral load of 50–399 HIV RNA copies/mL at 36 weeks
pre-labour CS should be considered taking into account: - the actual viral load - the trajectory of the viral load - length of time on treatment - adherence issues - obstetric factors - woman’s views
Mode of delivery for pregnant HIV +ve women with plasma viral load of ≥400 HIV RNA copies/mL at 36 weeks
pre-labour CS
Can HIV positive pregnant women be offered Vaginal birth after CS
VBAC can be offered if
VL <50 HIV RNA copies/mL
Can HIV positive pregnant women have a water birth after CS
Scant safety evidence to support water births I
Women who choose a water birth should be supported
where the viral load is <50 HIV RNA copies/mL
Neonatal management for the prevention of vertical transmission of HIV
for Very low risk infants
Infant PEP should be started within 4 hours of delivery
VERY LOW RISK
If ALL of the following criteria are met:
• The woman has been on cART >10 weeks
• 2 documented maternal HIV VL <50 HIV RNA during pregnancy at least 4 weeks apart;
• Maternal HIV viral load <50 HIV RNA copies/mL at or after 36 weeks
= 2 weeks zidovudine monotherapy recommended i
Neonatal management for the prevention of vertical transmission of HIV
for low risk infants
LOW RISK = Not all criteria for very low risk are met.
BUT maternal VL <50 HIV at time of delivery
OR infant born prematurely (<34 weeks) but most recent maternal HIV viral load is <50 HIV RNA copies/mL.
= zidovudine monotherapy extended to 4 weeks
Neonatal management for the prevention of vertical transmission of HIV
for high risk infants
HIGH RISK = maternal birth HIV viral load is known or likely to be >50
Use combination PEP
What factors increase the risk of HIV transmission via breast milk when women are not on cART
Detectable HIV viral load
Advanced maternal HIV
Longer duration of breastfeeding
Breast and nipple infection/inflammation
Infant mouth or gut infection/inflammation
Mixed feeding, in particular solid food given to infants <2 months age
What treatment should be offered to women with HIV who are advised not to breastfeed
offere cabergoline to suppress lactation
In what circumstances may HIV positive women be supported to breastfeed in the UK
Women virologically suppressed on cART
+ good adherence
+ who choose to breastfeed
should be supported t
Inform about the low risk of transmission of HIV through breastfeeding
and the requirement for extra maternal and infant clinical monitoring - monthly review incl VL
For women living with HIV when should cervical Cytology should be scheduled post-partum
Cytology should be scheduled 3 months post-delivery
SE of nevirapine
Nevirapine = NNRTI (non-nucleoside reverse transcriptase inhibitor)
10% experience grade 3 - 4 hepatotoxicity
some require liver transplant or die
What is in kaletra
Kaletra = lopinavir + ritonavir
= PI (protease inhibitor)
SE of kaletra
nausea and vomiting
diarrhoea
hyperlipidaemia
co-adminisgtered with an anti-emetic and anti-diarrhoea if used for PEPSE (not first line for PEPSE)
What class of ARV is Maraviroc
CCR5 receptor antagonists
SE of Maraviroc
few SE
well tolerated
If a HIV +ve patient has a CD4 count <200/mm3 what should they recieve in addition to ARVs?
CD4 count < 200/mm3
should receive prophylaxis against Pneumocystis jiroveci pneumonia
= co-trimoxazole
Signs of PCP infection
CXR: bilateral interstitial pulmonary infiltrates (can present with other x-ray findings e.g. lobar consolidation or may be normal)
Exercise-induced desaturation.
Sputum often fails to show PCP
Bronchoalveolar lavage (BAL) often needed to demonstrate PCP (silver stain shows characteristic cysts)
Symptoms of PCP
SOB dyspnoea dry cough fever very few chest signs
HIV +ve patient - CD4 <200
Treatment of PCP
co-trimoxazole
IV pentamidine if severe
steroids if hypoxic ( reduce risk of respiratory failure and death)
What additional baseline
investigations do pregnant women who are newly diagnosed with HIV require (BHIVA)
No additional baseline investigations
Those routinely offered
What proportion of children diagnosed with HIV in the UK were born abroad?
2 / 3
what psychosocial issues may exist around HIV and pregnancy
The majority engage well with care during pregnancy
psychosocial challenges may exist such as: stigma discrimination poor mental health unemployment lack of financial resources immigration status housing concerns lack of social support intimate partner violence / gender-based violence substance misuse
Recommendations regarding psychosocial care of women newly diagnosed with HIV during pregnancy
- significant psychosocial stress / trauma
- complex mix of emotional, psychosocial, relationship, economic +/- legal issues.
- prompt link to HIV care
- offer psychological support soon after diagnosis
- support to inform others - partner / social support network
- encourage timely partner testing during the pregnancy
- HIV testing of existing children should be raised
Recommendations regarding perinatal mental health assessment in HIV positive pregnant women
Assessment of antenatal and postnatal depression should be undertaken
at booking
4–6 weeks postpartum
3–4 months postpartum
what sexual health screening is recommended for pregnant women newly diagnosed with HIV
Screen for STIs
and for BV
Management of a HIV positive pregnant women with abnormal cervical cytology
undergo colposcopy in late first or early second trimester
For low-grade changes triaged to colposcopy on the basis of a positive HPV test - the assessment may be delayed until after delivery.
Management of a HIV positive pregnant women who requires colposcopy or cervical cytology after cervical treatment but becomes pregnant in the interrim?
assessment may be delayed until after delivery
Do not delay, (unless CI) if it is follow-up after treatment for cervical glandular intraepithelial neoplasia
Recommendations regarding resistance testing for women newly diagnosed with HIV during pregnancy
HIV resistance testing should be completed and results available prior to initiation of ARVs
EXCEPT - late-presenting women (after 28 weeks)
Recommendations regarding resistance testing and ART initiation for women newly diagnosed with HIV during pregnancy - presenting after 28 weeks
Start cART without delay
modify regimen once the resistance test is available
Recommendations regarding CD4 cell count testing for women newly commencing ART during pregnancy
CD4 cell count at initiation of cART
Plus at delivery
even if starting at CD4 >350 cells
Recommendations regarding HIV VL testing for women newly commencing ART during pregnancy
HIV viral load performed 2–4 weeks after commencing cART
at least once every trimester
at 36 weeks
at delivery
Management of a woman who has initiated cART during pregnancy and has not suppressed plasma
viral load to <50 HIV
- Review adherence
- Review concomitant medication;
- Perform resistance test if appropriate;
- Consider therapeutic drug monitoring (TDM);
- Optimise to best regimen;
- Consider intensification
If a HIV positive pregnant woman is not on ART when should it be commenced?
- As soon as able in 2nd T where baseline VL
≤30,000 copies/mL - Start of 2nd T or ASAP thereafter if baseline VL 30,000–100,000 copies/mL
- Within 1st T if VL >100,000 copies/mL and/or CD4
count < 200 cells/mm
All women should have commenced ART by week 24
A woman who presents after 28 weeks should start ART without delay
If ART commenced in pregnancy what should be started?
Start Tenofovir DF or Abacavir
with Emtricitabine or Lamivudine
Third agent - efavirenz or atazanavir
when is the only time that Zidovudine monotherapy is considered in HIV +ve pregnant women
only used in women declining cART
with a viral load of <10,000
and willing to have a caesarean section
Management of an untreated HIV +ve woman presenting in labour at term
STAT dose - Nevirapine 200 mg
Commence oral zidovudine 300 mg and lamivudine 150 mg BD
And raltegravir 400 mg BD
And IV zidovudine for the duration of labour
Management of a women presenting in labour or with spontaneous rupture of the membranes (SROM) without a documented HIV test result?
Advised to have an urgent HIV test.
4th gen POCT and send serum sample
Act immediately on a postitive result - initiate interventions to reduce vertical transmission
recommended investigations on diagnosis of new HBV infection in a pregnant F with HIV co-infection?
Confirm viraemia
Quantitative HBV DNA,
‘e’ antigen status
AND hepatitis A, C and D tests
Test to assess hepatic inflammation/fibrosis and liver function
LFTs repeated at 2 + 4 weeks after commencing ART then monitored regularly throughout pregnancy and postpartum
Which ARVs are recommended for treatment of pregnant women with HIV and HBV co-infection?
Tenofovir DF and emtricitabine or lamivudine should form the backbone
What is the recommendation regarding delivery route for a pregnant woman with HIV and HBV co-infection
Vaginal delivery can be recommended
IF the HIV VL is fully suppressed on ART,
Irrespective of HBV viral load
When is HAV vaccination recommended in pregnancy non-immune women with HBV and HIV co-infection
HAV vaccine recommended after the first trimester
- 0 and 6 months
UNLESS CD4 count <300 = give an additional dose = 0, 1 and 6 months
Management of an infant born to a woman with HBV
Neonatal immunisation +/- hepatitis B immunoglobulin commenced within 24 hours of delivery
BHIVA recommendations on invasive pre-natal diagnostic tests for women who are HIV +ve
Deferred until HIV viral load suppressed to <50 HIV RNA copies/mL
Can ECV be offered to HIV +ve pregnant women
Yes - if on ART and plasma viral load <50 HIV RNA
copies/mL.
HIV +ve pregnant women can be offered a vaginal delivery if the VL is less than……
plasma viral load of <50 copies/mL at 36 weeks
planned vaginal delivery should be supported
Recommended delivery method for HIV +ve pregnant women with a plasma viral load of 50-399 copies/ml at 36 weeks?
Consider pre-labour CS Take into account the actual viral load VL trajectory Duration on treatment Adherence issues Obstetric factors Patient preference and views
For a HIV +ve patient with SROM in what timeframe should delivery be aimed for?
In all cases of term pre-labour SROM in HIV +ve women
Aim for delivery within 24 hours
When is Intrapartum intravenous zidovudine infusion recommended?
- women with a HIV VL >1000 copies/mL who present in labour or with SROM or are admitted for Pre-labour CS
- untreated women presenting in labour /with SROM and current VL is not known
- Consider in women on ART with a plasma HIV VL between 50 and 1000 copies/mL.
BHIVA advice re PEP for infants of HIV +ve mothers
2/52 zidovudine monotherapy if infant = V Low risk
- mother on ART > 10 weeks
AND
- 2 documented HIV VL <50 during pregnancy at
least 4 wk apart
AND
- Maternal VL <50 HIV at /after 36/40
Extend to 4 weeks zidovudine monotherapy:
• If the criteria above not all fulfilled but maternal HVL <50 HIV or infant born <34 weeks but most recent maternal VL <50
If infant at HIGH RISK - Use combination PEP = zidovudine, lamivudine and nevirapine
- maternal VL is >50 on day of birth, uncertain or unknown VL
when should neonatal PEP should be commenced?
As soon as possible after birth
At least within 4 hours
Maximum duration of infant PEP advised by BHIVA
4 weeks
Factors which reduce vertical transmission of HIV
Reduce risk from 25-30% to 1-2%
- maternal antiretroviral therapy
- mode of delivery (caesarean section)
- neonatal antiretroviral therapy
- infant feeding (bottle feeding)
Toxoplasmosis accounts for what % of cerebral lesions in patients with HIV
50%
Symptoms of toxoplasmosis in patients with HIV
constitutional symptoms
headache
confusion
drowsiness
CT findings of toxoplasmosis in HIV +ve patient
CT head
single or multiple ring enhancing lesions
mass effect may be seen
management of toxoplasmosis
management: sulfadiazine and pyrimethamine
What stains with India ink
Cryptococcus neoformans
Most common cause of diarrhoea in HIV +ve patients
Cryptosporidium = most common cause of diarrhoea in patients with HIV infection.
Mycobacterium avium intracellulare and giardiasis are known causes of diarrhoea in HIV patients but are not as common
in what % of patients is HIV seroconversion symptomatic
60 - 80%
typical presentation of HIV seroconversion illness
Occurs 3-12 weeks after infection
sore throat lymphadenopathy malaise, myalgia, arthralgia diarrhoea maculopapular rash mouth ulcers rarely meningoencephalitis
Window period for HIV testing
4 weeks for 4th generation tests
12 weeks for all other tests
In patients with HIV
which infections pose a greater risk of complications
hepatitis B
hepatitis C
syphilis
herpes simplex virus
How often should HIV+ ve positive patients be offered an STI screen
Annually - regardless of history
or more often based on risk / history
How often should HIV+ve positive patients be offered a syphilis blood test
at baseline
and 3-monthly intervals - taken as part of the routine HIV blood set to detect asymptomatic syphilis
How often should HIV+ve positive patients be offered an Hep B / C blood test
screen at baseline
If HBV negative offer vaccination
then offer Hep B / C screen annually in those who have exposure risks and are not immune to HBV
BHIVA recommendations for STI and hepatitis screening at Baseline in patients diagnosed with HIV
Baseline
- full STI screen
- include syphilis serology f
- include pharyngeal and rectal NAAT for MSM ( heterosexual women depending on history)
- Hepatitis A ( gG or total)
- Hepatitis B (Surface antigen - HBsAg, Anti-core total antibody - anti-HBc, Anti-surface antibody - anti-HBs)
- Hepatitis C (antibody)
BHIVA recommendations for STI and hepatitis screening annually in patients diagnosed with HIV
Annually
- NAAT for GC / CT
- Syphilis serology if partner change since the last test;
- Hepatitis B
- Hepatits C (in at-risk patients)
BHIVA recommendations for STI and hepatitis screening Three-monthly in patients diagnosed with HIV
3-monthly screening for STIs
if high risk factors for acquisition
e.g. MSM / frequent partner change / chemsex / IVDU / chaotic lifestyle / CSW / recent tattoo abroad / recent blood transfusion abroad
BHIVA recommendations for Hep C screening in patients diagnosed with HIV
HCV antibody at baseline
at least annually
Anti-HCV and HCV-PCR if raised transaminases or recent high-risk exposure
(If prior HCV clearance do HCV-PCR only)
recommendation for cervical screening frequency in women living with HIV
annually
Advice for patients living with HIV regarding conception options when partner is HIV-negative
If VL suppressed on ART for at least 6 months
and no evidence of an STI
- timed (with ovulation) condomless sex can be recommended
If detectable HIV-RNA despite optimal ART - consider PrEP-C ( for Conception)
Pre-pregnancy health recommendations for women living with HIV
- Folic acid (400mcg daily) commenced prior to conception If on folate antagonists (e.g. co-trimoxazole) or has other indications give folic acid 5mg throughout pregnancy.
- general lifestyle advice - alcohol, smoking, recreational drugs, ideal weight
- vitamin D supplementation
- sexual health screens
- if CD4 count <200 advise deferring pregnancy until virological suppression and immune reconstitution are attained
What is TOCS and when can it be recommended
In context of HIV
timed ovulatory condomless sex (TOCS)
can be recommended if HIV VL undetectable for >6 months
adherence is good
no concomitant STI in either partner
Based on HPTN 052 and PARTNER studies
What is sperm washing
HIV positive partner’s sperm is centrifuged to separate spermatozoa from seminal fluid and associated non-sperm cells.
When may sperm washing be recommended
HIV plus coinfection with Hepatitis B or C
What investigations are recommended for women attempting to conceive via timed UPSI in a zero-discordant couple
Blood Tests
- HIV
- Hepatitis B + C
- Syphilis
- FSH, LH and Oestradiol days 2-5 of cycle
- Progesterone 7 days before expected day of next period (usually day 21)
- Prolactin & thyroid function if history of amenorrhoea/oligomenorrhoea
- Rubella serology
- STI Screen - NAAT chlamydia + gonorrhoea
what is the recommended timeframe to try to conceive for before referral to fertility team for women attempting to conceive via timed UPSI where their partner is HIV + ve
F <35yo - try for 6-12 months
F >35 - try for 6 months
What investigations are recommended for the man when attempting to conceive via timed UPSI (in serology-discordant couples)
Blood Tests
- HIV
- Hepatitis B + C
- Syphilis
- semen analysis
- STI Screen - NAAT chlamydia + gonorrhoea
Which contraceptives can be used with NRTI ARVs?
NRTI class of ARVs are renally eliminated are not metabolised by CYP450 nor glucuronidation pathways
can be used with ALL contraceptives
which contraceptive methods can be used with the NNRTI - efavirenz
and why
efavirenz
both inhibits and induces enzyme pathways involved in metabolising ethinyl estradiol (EE) = net neutral effect
BUT
significantly lowers progestogen levels
Hence only safe to use with IUD, LNG-IUS and POIC
FSRH advice on women using enzyme inducing ARTs and requiring EC
recommend IUD
if declined - offer double dose levonorgestrel
UPA should be avoided
What psychological factors may erectile dysfunction be associated with in the context of HIV
fear of onward transmission of HIV disclosure concerns changes in body image stigma issues around condom usage
What % of HIV diagnoses are made via partner notification?
<3% only
History to be taken for all newly diagnosed HIV-positive patients
• General medical (including symptoms) • Psychosocial • Sexual and reproductive health • Past and current co-morbidities • Concomitant medications • Lifestyle • HIV status of sexual partners and children • Conception issues • Knowledge and beliefs about HIV infection, HIV transmission and HIV treatment • Partner notification • HIV testing of children • Current or previous intimate partner violence • Vaccination • Lifetime travel
- current or previous mental health problems
- neurocognitive problems
- current social and welfare situation
- employment status
- immigration status
Baseline examination for all newly diagnosed HIV-positive patients
weight, height, BMI,
blood pressure
waist circumference
Baseline investigations for all newly diagnosed HIV-positive patients
• Confirmation of HIV-1/-2 status • Test for primary HIV infection (PHI) • HIV-1 plasma viral load • HIV-1 drug-resistance test • CD4+ T cell count (absolute and percentage) • Hepatitis A virus IgG (or total) • Hepatitis B tests • Hepatitis C virus antibody • full STI screen (including syphilis) • Measles/varicella antibodies (according to vaccination/infection history) • Full blood count • Renal profile • Liver profile • Bone profile • Dipstick urinalysis +/- urine protein/creatinine ratio
- HLA-B*57:01 if abacavir therapy being considered
- Viral tropism test if a CCR5 inhibitor being considered
- Cardiovascular risk assessment if >40yrs (QRISK2)
- FRAX tool if >50 years / post-menopausal F or other high risk
And for women:
• Cervical cytology (if aged 25-65 and not done in the last 12m or never done)
• Rubella in women of child-bearing potential
Monitoring in the first 6 months after starting ART
- Adherence and tolerability check
- Examination according to any symptoms
- U+Es
- LFTs
- Urine dipstick
- FBC: only if patient is unwell or started zidovudine
- CD4 count - After 3 months if baseline <350
- CD4 count at 6 months if it was still <350 at 3 months post-ART.
• HIV viral load - Measure at 1, 3 + 6 months
Monitoring of patients established on ART and with the viral load suppressed
Annual
• HIV viral load
• CD4 count
• FBC / renal / liver / bone profiles
• urine dipstick
• STI screen
• Hepatitis A/B /C infection/immunity status
• Cervical smear for women if not done by GP
• Metabolic assessment: (if age >40 years) lipid profile, HbA1c
History at each visit: • medication history + recreational drug use • Understanding of dosing instructions • Adherence • Mood • Adverse effects • Patients’ concerns about medication
Examination - based on symptoms
Additional monitoring of patients presenting with advanced disease (CD4 cell count <200 at first presentation)
If symptoms test for:
Toxoplasma
Cryptococcus
mycobacterial infection
Monitor for IRIS - esp within 3 months of starting ART
What does NRTI stand for
Nucleoside reverse transcriptase inhibitors = NRTI
e.g. Truvada = Tenofovir DF and emtricitabine
Abacavir
lamivudine
zidovudine
What does INI stand for
Integrase inhibitors = INI
E.g. Raltegravir
Elvitegravir
Dolutegravir
What does NNRTI stand for
Non-nucleoside reverse transcriptase inhibitors = NNRTI
E.g. Nevirapine
Efavirenz
etravirine
rilpivirine
Serious side effect reported of etravirine
Stephens Johnson Syndrome
What does PI stand for
Protease Inhibitors = PI
E.g. Kaletra (lopinavir/ritonavir)
darunavir
atanzavir
Side effects of Kaletra (lopinavir / ritonavir)
hyperlipidaemia
frequently causes gastrointestinal disturbances
necessitating provision of anti-diarrhoeal and antiemetic medication
Side effects of daurnavir
frequently causes gastrointestinal disturbances
May require provision of anti-diarrhoea and antiemetic
Which medication is a CCR5 receptor antagonist
Maraviroc
well tolerated
worldwide what % of HIV is transmitted by IVDU
1 in 10 new diagnoses worldwide due to IVDU
Outside of the African continent what % of HIV is transmitted by IVDU
1 in 3 new diagnoses
Complications of PCP
Respiratory failure / ARDS
Requiring ventilation
Death
Worsening symptoms after treatment started
Pulmonary cyst formation
Harmatogenous spread to - bone marrow, liver, spleen, eyes, GI tract, Lymph nodes
Mortality from PCP
10 -20%
Increases to 65% if ventilation is required
Risks of dolutegravir in pregnancy
?increase in birth defects
Tsepamo study - Botswana
Neural tube defects
Opportunistic infection prophylaxis
Trimethoprim + sulfamethoxazole - for PCP and toxoplasmosis prophylaxis
Dapsone + pyrimethamine = alternate PCP prophylaxis
Azithromcyin or Clarithromycin - MAC prophylaxis
Itraconazole - histoplasmosis, penicilliosis prophylaxis
Atovoquone - alt for PCP prophylaxis
Isoniazid + pyridoxine - for latent TB prophylaxis
Rifampicin / rifabutin - for isoniazid resistant latent TB prophylaxis
What vaccinations should be offered to HIV +ve patients
Hep A Hep B Pneumococcal PCV13 Diptheria Tetanus HPV Meningococcal ACWY Flu
AVOID live vaccines
EXCEPT - do give - MMR and varicella vaccines if CD4 >200
Management of a HIV +Ve patient exposed to chickenpox / shingles when CD4 <200
Give aciclovir or valaciclovir 7 - 10 days
What 2 types of HIV POCT exist
INSTI - 20 second result - tests for HIV ab only = 3m window period
Determine (biosure) - 20 minutes result - tests for HIV ab and p24 antigen = 4 week window period
How to perform the INSTI HIV POCT
patient wash and warm hands
Fingerprick + bleed
add a drop of blood to bottle 1 + shake
Pour bottle 1 into the well + wait until soaked in
Add bottle 2 into the well + wait until soaked in
Add bottle 3 to the well
wait ~20 seconds
1 dot = non reactive
2 dots = reactive
no dots = invalid
How to perform the determine HIV POCT
patient wash and warm hands Fingerprick + bleed use capillary tube to collect blood touch capillary tube to the sample pad on the test strip wait 1 minute and add buffer solution wait 20 minutes and read result
1 line = control
2 lower lines = for antibody and antigen
