IC18 STI Flashcards
HIV: mode of transmission
via specific body fluids
Blood, semen, genital fluids, breast milk
HIV: Risk factors
(who to conduct testing for)
IV drug users
Person who have unprotected sex with multiple partners
Man who have sex with man
Commercial sex workers
Persons treated for STDs ⇒ increased risk of HIV
Recipients of multiple blood transfusion
Persons who have been sexually assaulted
Pregnant women
HIV: clinical presentation
(1) acute (primary) infection
Occurs soon after contracting HIV
Flu-like illness: swollen lymph nodes, fever, malaise & rash ⇒ lasts 2-3 weeks
HIV: clinical presentation
(2) asymptomatic
No signs & symptoms
Persists for many years
HIV: clinical presentation
(3) persistent generalised lymphadenopathy
Persistent unexplained lymph node enlargement in neck, underarms & groin
More than 3 months of symptoms
HIV: clinical presentation
(4) AIDS & related conditions
diagnostic criteria & symptoms (organs involved & systemic s)
Requirements for AIDS diagnosis:
* AIDS = CD4 <200 cells /mm3 or presence of AIDS-defining diseases
Healthy individuals: CD4 500-1200 cells /mm3
* Immune system too weak to fight against invading virus & bacteria
* Person succumb to Opportunistic infections
Organs involved: lung, eyes, GIT, nervous system & skin
Systemic symptoms: fevers, unexplained weight loss, diarrhoea
Rare cancers
Goals of anti-retroviral therapy
- Reduce HIV-associated morbidity & mortality
- Prolong duration & quality of survival
- Restore & preserve immunologic function
To avoid reaching state of being immunocompromised; maintain CD4 T cell count - Maximally & durably suppress plasma HIV viral load to undetectable levels
- Prevent HIV transmission
Surrogate markers of HIV
- CD4 Cell count
- Viral load
Surrogate markers of HIV: CD4 count
what it indicates
Normal individuals: 500-1200 cells/ mm3
Indicator of immune function
strongest predictor of subsequent disease progression + survival
Surrogate markers of HIV: CD4 count
purpose
To determine urgency for initiating antiretroviral therapy
* Note: current → to start treatment when patient is infected with virus to prevent CD4 cell count from decreasing
* Late start to treatment = unlikely recovery of CD4 cell count to normal levels
To assess response to antiretroviral therapy (compare with initial diagnosis)
(1) assessed at baseline, (2) every 3 to 6 months after treatment initiation & (3) every 12 months after adequate response
To assess need for initiating/ discontinuing prophylaxis for opportunistic infections
Surrogate markers of HIV: CD4 count
effective treatment definition
increase in CD4 count in the range of 50 to 150 cells/mm3 during the first year of therapy
Surrogate markers of HIV: Viral load
indication
Amount of virus in plasma
Most important indicator of response to antiretroviral therapy
Help with predicting clinical progression
Surrogate markers of HIV: Viral load
Assessment timeline
- Before initiation of therapy
- Within 2-4 weeks after treatment initiation OR modification (no later than 8 weeks)
- Every 4-8 weeks until viral load suppressed
- Those on stable regime & suppressed viral load ⇒ every 3-6 months
Surrogate markers of HIV: Viral load
effects of treatment
achieve viral suppression by 8-24 weeks
* No longer have detectable HIV RNA levels
earlier ART initiation
indication & requirements
For all HIV-patients regardless of CD4 cell count
adherence: Require at least 95%, if not have risk of resistance
earlier ART initiation: benefits
- Maintenance of higher CD4 count & prevention of potentially irreversible damage to immune system
- Decreased risk for HIV-associated complications
- Decrease risk of non-opportunistic conditions
CVD, renal disease, liver disease & non-AIDS-associated malignancies and infection - Decreased risk of HIV transmission ⇒ positive public health implications
earlier ART initiation: limitations
- Development of treatment-related SE & toxicities
- Development of drug resistance
Due to incomplete viral suppression; especially non-adherence
Loss of future treatment options - Transmission of drug-resistant virus for those without full virologic suppression
Important to check for resistance pattern of virus before initiating treatment - Lesser time for patient to understand HIV and its treatment + preparation for need of adherence
- Increased total time on medications → greater treatment fatigue
- Increased costs
Recommended combinations (patients naive to ART)
2 NRTIs + 1 INSTI [First line]
1 NRTIs + 1 INSTI
Recommended combinations: 1 NRTI & 1 INSTI requirements
- HIV RNA >500k copies/ mL (extremely high)
- HBV coinfection
HBV → requires 2 AV against HepB virus (tenofovir, emtricitabine, lamivudine) - Starting on ART before results of HIV genotypic resistance testing/ HBV testing
Must confirm that patient does not have co-infection of HBV & resistance against drug before treatment
ART drug classes
- NRTI
- INSTI
- NNRTI
- PI
- fusion inhibitor
- CCR5 antagonist
(1) NRTI: drugs
lamvudine
abacavir
zidovudine
emtricitabine
tenofovir
(1) NRTI: Advantages
Established in combination ART
Renal elimination → fewer DDI
(1) NRTI: disadvantages
AE related to mitochondrial toxicity → rare but serious
* Lactic acidosis & hepatic steatosis (fatty infiltration)
* Morphologic complication ⇒ Lipoatrophy (lost of fat)
* Zidovudine>Tenofovir=Abacavir=Lamivudine
Requires dose adjustment in renally impaired patients (except abacavir)
(1) NRTI: Adverse effects
lamvudine, tenofovir, emtricitabine
lamvudine
Minimal toxicity; N/V/D
tenofovir
Minimal toxicity; hyperpigmentation, N/D
emtricitabine
* N/V/D
* Possible renal impairment
* Decrease in bone mineral density ⇒ increased risk of osteoporosis & osteopenia
(1) NRTI: Adverse effects
zidovudine, abacavir
Abacavir
* N/V/D
* Hypersensitivity reaction in patients with HLA-B*5701
Discontinue if occurs & do not rechallenge
Require testing for HLA-B5701 before initiation
- Association with MI ⇒ avoid in high CVD risk patients
zidovudine
* N/V/D
* Myopathy
* Bone marrow suppression ⇒ causes anemia/ neutropenia
(To monitor FBC)
(2) INSTI: drugs
bictegravir
raltegravir
elvitegravir
dolutegravir
(2) INSTI: Advantages
B&D
Bictegravir & dolutegravir ⇒ good virologic effectiveness
High genetic barrier to resistance [B&D > R&E]
Generally well tolerated
(2) INSTI: Disadvantages
bioavailability, DDI
Bioavailability lowered by concurrent administration of polyvalent cations
Bictegravir, dolutegravir & elvitegravir ⇒ CYP 3A4 substrates
(2) INSTI: Adverse effects
common ones
weight gain, diarrhoea, nausea & headache
Depression & suicidality in those with pre-existing psychiatric conditions
(2) INSTI: Adverse effects
bictegravir & elvitegravir
increase SCr
Inhibits tubular secretion of creatinine
(2) INSTI: Adverse effects
raltegravir
Pyrexia
Elevation of CK ⇒ rhabdomyolysis
(3) NNRTI: drugs
efavirenz
Rilpivirine
(3) NNRTI: Advantages
- Long t1/2 ⇒ OD dosing
- Less metabolic toxicities than with some PIs
Hyperlipidemia, insulin resistance
(3) NNRTI: Disadvantages
GB, CR, DDI, S, Q
- Low genetic barrier for resistance
- Cross resistance among approved NNRTIs
- Skin rash, SJS [R < E]
- Potential for CYP450 drug interactions → inducers & inhibitors
Efavirenz: CYP3A4 substrate, CYP2B6 and 2C19 inducer
Rilpivirine: CYP3A4 substrate, oral absorption is reduced with increased gastric pH; use with PPIs is contraindicated. - QTc prolongation
(3) NNRTI: AE
Efavirenz, Rilpivirine
Efavirenz
* Rash
* Hyperlipidemia: increased LDL-C & TG
* Neuropsychiatric SE: dizziness, depression, insomnia, abnormal dreams, hallucination
* Hepatotoxicity
Rilpirivine
CNS: Depression & headache
(4) protease inhibitor: drugs
Liponavir
Azatanavir
Darunavir
Fosamprenavir
Ritonavir
(4) protease inhibitor: Advantages
High genetic barrier to resistance
(4) protease inhibitor: Disadvantages
- Metabolic complications → dyslipidemia, insulin resistance
- GI SE → N/V/D
- Liver toxicity (especially with chronic hepatitis B or C)
- CYP3A4 inhibitors & substrates: potential for DDI
- Morphologic Complications → Fat maldistribution (Lipohypertrophy)
- Increased risk of osteopenia/osteoporosis
(4) protease inhibitor: characteristics
ritonavir
- Potent CYP3A4, 2D6 inhibitor
- PK enhancer → combined with other PI [Lopinavir/ritonavir] to increase the other PI concentration levels
SE: paresthesia (numbness of extremities) & taste perversion
(4) protease inhibitor: characteristics
azatanavir
(+) Good GI tolerability & less lipid effects
* Absorption depends on low pH
Contraindication with PPIs
SE: hyperbilirubinemia, prolong QT interval, skin rash
(4) protease inhibitor: characteristics
darunavir
(+) Good GI tolerability & less lipid effects
(-) Skin rash & concern for SJS
Due to sulfonamide component
(5) fusion inhibitor: drug & characteristics
administration & DDI
Enfuvirtide
SC injection BD
no DDI
(5) fusion inhibitor: AE
- Injection site reaction→ erythema/ induration, nodules/ cyst, pruritis, ecchymosis
- Rare hypersensitivity → fever, chills, decrease BP, rash
- Increased bacterial pneumonia
(6) CCR5 antagonist: drug
maraviroc
(6) CCR5 antagonist: requirement
Only for those with strains of HIV using CCR5 receptor to enter CD4 cells
* Need co-receptor tropism assay before initiation (to check which receptor HIV uses to enter cells)
* Must be CCR5 predominant
(6) CCR5 antagonist: potential DDI & AE
Potential DDI: CYP3A4 substrate
ADR:
Abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, upper respiratory tract infections, hepatotoxicity, orthostatic hypotension
STI caused by bacteria
Syphilis: Treponema pallidum
Gonorrhoea: Neisseria gonorrhoeae
Non-gonococcal urethritis
Chlamydia
STI caused by virus
herpes simplex virus (HSV)
HIV
Mode of transmission for STIs
- Mainly by sexual contact with infected person
-
Direct contact of broken skin with open sores, blood or genital discharge
Must be deep/ big - Receiving contaminated blood
Important to start on post-exposure prophylaxis
Usually screened to ensure no STI in blood - From infected mother to child
During pregnancy → ie: syphilis, HIV
During childbirth → ie: chlamydia, gonorrhoea, HSV
Breastfeeding → ie: HIV
RF for STIs
- Unprotected sexual intercourse
- Number of sexual partner
Those with multiple sexual partners→ more likely to acquire & transmit STI
Those with sexual contact with people who have multiple sexual partners - MSM
- Prostitution (CSW) → covers first 2 points
- Illicit drug use → ie sharing of needle by IV drug users
individual prevention methods of STI
- Abstinence & reduction of number of sexual partners
long-term, mutually monogamous relationship with an uninfected partner - Barrier contraceptive methods
male latex condoms when used consistently & correctly - Avoid drug abuse & sharing needles
- Pre-exposure vaccination
HPV (Human papillomavirus), Hepatitis B - Pre- and Post-exposure prophylaxis → HIV
Pre: if viral load is not suppressed, partner is at risk of infection → to take AV pills continuously
Post: after possible exposure to virus
(B) Gonorrhoea: causative organism
Neisseria gonorrhoeae
(B) Gonorrhoea [&chlamydia] : transmission
sexual contact, mother-to-child during childbirth
(B) Gonorrhoea: diagnostic method
gram-stain of genital discharge, culture, NAAT
(B) Gonorrhoea [&chlamdymia] : possible infection to other sites
Urethritis → urethra; Cervicitis → cervix; Proctitis → rectal area; Pharyngitis → throat; Conjunctivitis
Disseminated → throughout the body
(B) Gonorrhoea [&chlamdymia] : clinical presentation (uncomplicated)
male & female
both
Dysuria
Urinary frequency
Male
Purulent urethral discharge
female
Mucopurulent vaginal discharge
(B) Gonorrhoea [&chlamdymia] : clinical presentation (complicated)
male & female
both
disseminated disease
male
Epididymitis
Prostatitis
urethral stricture
female
Pelvic inflammatory disease
Ectopic pregnancy, infertility
(B) Gonorrhoea: pharmacological management
first line & alternative
First line
Ceftriaxone:
* 500 mg IM single dose for those <150kg
* 1g IM single dose for those ≥150kg
Alternative (if ceftriaxone unavailable)
* Gentamicin 240 mg IM in single dose AND
* Azithromycin 2g PO in single dose
PO doxycycline 100 mg BD x7 days if chlamydia infection not excluded
(B) Chlamdymia: causative organism
Chlamydia trachomatis
(B) Chlamdymia: diagnostic test
NAAT
(B) Chlamdymia: pharmacological management
first line & alternative
First line
PO Doxycycline 100 mg BD x7 days
Alternative (if ceftriaxone unavailable)
PO Azithromycin 1g in single dose
OR
PO levofloxacin 500 mg OD x7 days
Possible to use azithromycin as first line if adherence is of concern
(B) Chlamdymia: requirements for testing of cure
pregnancy, non-adherence or symptoms persist
* Need to check for possibility of reinfection
(B) gonorrhea & Chlamdymia: management of sex partners
- Sex partners in last 60 days should be evaluated & treated
If last sexual exposure >60 days, to treat most recent partner - Abstain from sexual activity for 7 days after treatment to minimise disease transmission
- Abstain from sexual intercourse until all sex partners are treated to minimise risk of reinfection
(B) syphilis: causative organism
Treponema pallidum
(B) syphilis: transmission
sexual contact, mother-to-child (transplacental during pregnancy)
(B) syphilis: diagnosis
Darkfield microscopy of exudates from lesions
2 serological tests ⇒ more common
(B) syphilis: diagnosis
serological tests
- trepenomal test
- non-trepenomal test
(B) syphilis: trepenomal test
how it works, what it tells, limitation
- Use treponemal Ag to detect treponemal Ab (produced during infection)
- More sensitive & specific than non-treponemal test ⇒ used as confirmatory test
- May remain active for life → not for monitoring response to treatment
Ab remains present in body; not necessarily indicate current infection
(B) syphilis: non-trepenomal test
what it tells, how it works
- To determine if infection is CURRENT or PAST
- Use nontreponemal Ag (cardiolipin) to detect treponemal Ab
- Positive tests → presence of any stage of syphilis
- Result reported in quantitative VDRL/ RPR test = most dilute serum concentration with positive reaction
Result of 1:16 positive ⇒ 1:32 no reaction seen (no Ab at that dilution) -
Higher VDRL/ RPR = greater bacteria presence (more Ab produced)
Ab titre correlate with disease activity ⇒ used to monitor response to treatment - Non-treponemal test titres usually declines after treatment; becomes non-reactive with time
(B) syphilis: pharmacological management
primary/ secondary/ early latent (<1 year)
regimen & penicillin allergy (+ counselling)
IM Benzathine penicillin G 2.4 million units x1 dose
penicillin allergy
PO doxycycline 100 mg BD x14 days
Counselling
* Take with food to reduce GI upset
* Take with glass of water & maintain upright at least 30 mins to prevent heartburn
* Do not take with milk, Ca or Fe ⇒ take 2 hours apart
SE
GI, photosensitivity
(B) syphilis: pharmacological management
tertiary/ unknown duration/ late latent (>1 year)
regimen & penicillin allergy
IM Benzathine penicillin G 2.4 million units once a week x3 dose
penicillin allergy
PO doxycycline 100 mg BD x28 days
(B) syphilis: pharmacological management
neurosyphilis
regimen & penicillin allergy
IV crystalline (benzyl) penicillin G 3-4 million units q4h or 18-24 million units q24h x10-14 days
OR
IM procaine penicillin G 2.4 million units OD + PO probenecid 500 mg QID x10-14 days
penicillin allergy
IV/ IM ceftriaxone 2 g OD x10-14 days
Concerns for cross-sensitivity
* Skin prick test to confirm penicillin allergy
* To desensitise if necessary
(1) Daily low level of exposure of allergen (penicillin) → build up to therapeutic dose
(2) Continue at therapeutic dose → if miss dose, should restart low dose again
(B) syphilis: formulation
PenG
IM benzathine, IM procaine, IV crystalline
IM benzathine ⇒ released over a week (slower)
High sensitivity of syphilis from penG ⇒ low concentration of drug required
IM procaine ⇒ releases over a day + IV crystalline ⇒ high dose
Bacteria entering CSF → require high dose of penicillin G to reach CSF concentration
(B) syphilis: formulation
probenecid
purpose
reduces secretion of penicillin ⇒ increases concentration of penicillin in systemic circulation
* Cannot give IM procaine alone in neurosyphilis; unable to achieve high enough CSF concentration
(B) syphilis: response upon treatment
Jarisch-Herxheimer reaction = acute febrile reaction, frequently accompanied by headache, myalgia, and other symptoms that usually occur **within the first 24 hours after any therapy **for syphilis
* Antipyretics will help but not prevent
(B) syphilis: monitoring of response
syphilis & neurosyphilis, duration of tests
Primary / secondary/ Latent syphilis: Quantitative VDRL/ RPR at 3, 6, 12, 18 & 24 months (using blood)
* treatment success = decrease of VDRL or RPR titre by at least fourfold (ie: 1:64 to 1:16)
Neurosyphilis: CSF examination (Quantitative VDRL/ RPR) every 6 month until CSF normal
(B) syphilis: indication of treatment failure
- show sign & symptoms of disease
- Failure to decrease VDRL/ RPR titre by fourfold OR VDRL/ RPR titre increase
ie 1:16 to 1:64 - Retreat & re-evaluate for unrecognised neurosyphilis
(B) syphilis: management of partners
- All at risk sexual partners should be evaluated for STIs & treat if test positive
- Persons receiving syphilis treatment must abstain from sexual contact with new partners until the syphilis lesions are completely healed
(V) Genital herpes: causative agent
HSV2 mainly
(V) Genital herpes: transmission
transfer of body fluids and intimate skin-to-skin contact
(V) Genital herpes: infection timeline
development & healing of vesicles, viral shedding
Vesicles develop over 7-10 days; heal in 2-4 weeks
* Reactivation of virus → will have shorter healing time
Intermittent viral shedding from epithelial cells
* Possible even when person is asymptomatic
* Transmission can occur even without presence of vesicles
(V) Genital herpes: diagnosis methods
- patient hx
- virologic testing
- type-specific serologic test
(V) Genital herpes: diagnosis
patient hx
Previous lesions
Sexual contact with similar lesions at genitals
(V) Genital herpes: virologic test
NAAT (PCR) for HSV DNA from genital lesions
(V) Genital herpes: type specific serologic test
what is tested, problem for first-episode serology
Testing for Ab
- Ab to HSV develop during the first several weeks after infection & persist indefinitely
- Serology is not useful for first episode infection → takes between 6 & 8 weeks for serological detection following a first episode
Requires time for buildup of Ab to sufficient concentration for detection
Presence of HSV-2 antibody ⇒ anogenital infection
(V) Genital herpes: clinical presentation
first infection
- classical painful multiple vesicular or ulcerative lesions (When vesicles break)
- local itching, pain, tender inguinal lymphadenopathy (lymph at inguinal)
- Flu-like symptoms (ie: fever, headache, malaise) during first few days after the appearance of lesions
(V) Genital herpes: clinical presentation
recurrent
- Prodromal symptoms → mild burning, itching or tingling
- Symptoms less severe → less lesions, heal faster, milder symptoms
Due to previous immunity; presence of Ab reduces severity
(V) Genital herpes: supportive care & counselling
- Warm saline bath → relief discomfort
- Analgesia & anti-itch → symptomatic relief
- Good genital hygiene → prevent superinfection of bacteria
- Counselling about natural history
Inform that infection is lifelong + possible transmission even without vesicles; triggers for vesicles + reactivation is possible
(V) Genital herpes: drug choice
MOA, clinical effects, when to start
acyclovir & valacyclovir
Mechanism of action: inhibit viral DNA polymerase → inhibit DNA synthesis & replication
Clinical effects:
* Reduce viral shedding by 7 days
* Reduce duration of symptoms by 2 days
* Reduce time to healing of 1st episode by 4 days
Starting
Maximum benefit ⇒ initiate at earliest stage of disease (within 72 hours)
(V) Genital herpes: first episode
acyclovir
dose, F, t1/2, counselling points, SE
- PO 400 mg TDS x7-10 days
- IV 5-10 mg/kg q8h x2-7 days + PO for 10 days
For severe disease/ complications requiring hospitalisation/ herpes encephalitis
Usually for immunocompromised (will have higher viral load)
F = 10-20%; t1/2 ~3 hours
Counselling
* Take with/ without food
After food if have GI upset
* Maintain adequate hydration ⇒ prevent crystallisation in renal tubules
SE (general, non-specific)
Malaise, headache, N/V/D
(V) Genital herpes: first episode
valacyclovir
dose, F, t1/2, counselling points, SE
PO 1g BD x7-10 days
L-valine ester of acyclovir (prodrug)
Rapidly & almost completely converted to acyclovir & valine
F = 55%; t1/2 ~3 hours
* Can give higher dose & less frequently
Counselling: similar to acyclovir including hydration
SE: mainly headache
(V) Genital herpes: recurrent
definition
Median = 4 recurrences the year after first symptomatic episode
(V) Genital herpes: recurrent therapies
- chronic suppressive therapy
- episodic therapy
(V) Genital herpes: [1] chronic suppressive therapy
drug & dosing
PO Acyclovir 400 mg BD
PO valacyclovir 1 g OD
(V) Genital herpes: [1] chronic suppressive therapy
indications
- patients who have many recurrences
- Patients with complicated disease course (ie disseminated disease)
- immunocompromised hosts → may have severe disease state during reactivation of HSV
(V) Genital herpes: [1] chronic suppressive therapy
advantages
- reduces the frequency of recurrences by 70%–80% in patients who have frequent recurrences (ie: >6 recurrences per year)
- Most will have no symptomatic outbreaks ⇒ improved QOL
- decreased risk of transmission
in combination with consistent condom use & abstinence during recurrences
Reduction in chance of viral shedding + barrier method
(V) Genital herpes: [1] chronic suppressive therapy
disadvantages
Cost → daily dosing
Compliance → continuous dosing
(V) Genital herpes: [2] episodic therapy
when to start
when patient have prodromal symptoms OR vesicles present
(V) Genital herpes: [2] episodic therapy
drug & dose
Either one of the following:
* PO Acyclovir 800 mg
BD x5 days OR TDS x2 days
* PO valacyclovir 500 mg BD x3 days
* PO valacyclovir 1 g OD x5 days
(V) Genital herpes: [2] episodic therapy
advantage
- Shorten duration & severity of symptoms
- Less costly compared to chronic suppression
- Patient more likely to be compliant
(V) Genital herpes: [2] episodic therapy
disadvantage
- Requires initiation of therapy within 1 day of lesion onset or during the prodrome that precedes some outbreaks
- Does not reduce risk of transmission
Once patient is off AV → can shed virus & transmit HSV
(V) Genital herpes: management of sexual partners
- Symptomatic sex partners: evaluated & treated in the same manner as patients who have genital lesions.
- Asymptomatic sex partners of patients who have genital herpes should be questioned concerning histories of genital lesions, encouraged to examine themselves for lesions and seek medical attention early if lesions occur.
