IC18: STIs Flashcards
What are the risk factors for STIs? (5)
1) Unprotected sexual intercourse (no barrier method)
2) Number of sexual partners (have multiple sex partners or contact with someone with multiple sex partners)
3) MSM (Gay sex)
4) Prostitution (Commercial Sex worker, CSW)
5) Illicit drug use
Risk of being exposed to blood from contaminated needles
Higher chance of risky behaviour due to drug use
What are non-pharmacological advice for STI prevention?
1) Abstinence and reduction of number of sexual partners
Long term, mutually monogamous relationship with an uninfected partner
2) Barrier contraceptive methods
Male latex condoms when used consistently and correctly
3) Avoid drug abuse and sharing needles
4) Pre-exposure vaccination
HPV (Human papilloma virus), Hepatitis B
5) Pre- and Post- exposure prophylaxis
What are the symptoms of uncomplicated urogenital gonorrhea?
1) Dysuria
2) Urinary frequency
3) Purulent Urethral discharge (in males)/ Mucopurulent vaginal discharge (in females)
What diagnostic tests can be done for patient with gonorrhea?
1) Gram stain of genital discharge
2) Culture (done if suspect will have resistance to get AST)
3) NAAT (Nucleic Acid Amplification Test; PCR)
What is the treatment regimen for uncomplicated gonorrhea if patient is 100kg and the drug of choice is available?
Ceftriaxone 500mg IM single dose + PO Doxycycline 100mg BD x 7 days (if Chlamydia not excluded)
What is the treatment regimen for uncomplicated gonorrhea if patient is 151 kg and the drug of choice is available?
Ceftriaxone 1000mg IM single dose + PO Doxycycline 100mg BD x 7 days (if Chlamydia not excluded)
What is the treatment regimen for uncomplicated gonorrhea if the drug of choice is not available?
Gentamicin 240mg IM single dose + PO Azithromycin 2g single dose
- No need Doxycycline as Azithromycin can cover both Gonorrhea and Chlamydia
- AG to prevent Macrolide resistance
OR
PO Cefixime 800mg single dose (not available in SG)
How would you manage the sex partners of someone who has been diagnosed with Gonorrhea?
o Sex partners in the last 60 days should be evaluated and treated. If last sexual exposure > 60 days, the most recent partner to be treated.
o Abstain from sexual activity for 7 days after treatment (i.e. 7 days after receiving treatment and resolution of symptoms, if present).
o To minimize risk for reinfection, patients also should be instructed to abstain from sexual intercourse until all their sex partners have been treated.
How would you manage the sex partners of someone who has been diagnosed with Chlamydia?
o Sex partners in the last 60 days should be evaluated and treated. If last sexual exposure > 60 days, the most recent partner to be treated.
o Abstain from sexual intercourse for 7 days after single dose therapy, or until completion of a 7-day regimen and resolution of symptoms if present.
o To minimize risk for reinfection, patients also should be instructed to abstain from sexual intercourse until all their sex partners have been treated.
Is test of cure for Gonorrhea recommended in SG?
Yes
State when test for cure of Chlamydia necessary
Test of cure is not required unless specific concerns (e.g. pregnancy, non-adherence) or symptoms persist
State the recommended regimen for Chlamydia if patient is adherent
PO Doxycycline 100mg BD for 7 days
State the recommended regimen for Chlamydia if patient is non-adherent
PO Azithromycin 1g single dose
Which FQ may be used in Chlamydia as alternative regimen and state the regimen
PO Levofloxacin 500mg once daily for 7 days
What are the tests used to confirm a diagnosis of syphilis
Darkfield microscopy of exudates from lesions
* Look for spirochete (wriggly) bacteria
Requires 2 serological tests (mainstay): treponemal and non-treponemal tests
Compare and contrast the Treponemal and Non-treponemal tests.
1) Treponemal test use treponemal antigen while non-treponemal use non-treponemal antigen (e.g cardiolipin) to detect presence of trepnemal antibody
2) Treponemal test more sensitive and specific than non-treponemal test
3) Treponemal used as confirmation test but not for monitoring of response. Non-treponemal used to monitor response to treatment
4) Nontreponemal test titres usually declines after treatment and can become non-reactive with time. Treponemal test may remain reactive for life, hence not for monitoring response to treatment
What are examples of Treponemal tests?
a) T. pallidum Haemaggluntination test (TPHA)
b) T. pallidum passive particle agglutination assay (TPPA)
c) Venereal Disease Research Laboratory (VDRL) slide test
d) Rapid plasma reagin (RPR) card test
TPHA and TPPA
What are examples of non-Treponemal tests?
a) T. pallidum Haemaggluntination test (TPHA)
b) T. pallidum passive particle agglutination assay (TPPA)
c) Venereal Disease Research Laboratory (VDRL) slide test
d) Rapid plasma reagin (RPR) card test
VDRL, RPR
What is the result reported for VDRL/RPR test?
The most dilute serum concentration with a positive reaction (e.g. result 1:16 positive means at 1:32 no reaction seen) -> high antibody load = higher ratio (need more dilution till negative reaction)
What is the recommended regimen for a patient who was diagnosed with Syphilis in the doctors office today ? (Pt had syphilis symptoms 11 months ago but did not seek treatment; no penicillin allergy reported)
IM Benzathine penicillin G 2.4 million units x 1 dose
What is the recommended regimen for a patient who was diagnosed with Syphilis in the doctors office today ? (Pt had syphilis symptoms 11 months ago but did not seek treatment; penicillin allergy reported)
PO Doxycycline 100mg BD for 14 days
What is the recommended regimen(s) for someone with syphilis and presents today with difficulty walking due to gummatous lesions?
IM Benzathine penicillin G 2.4 million units once a week x 3 doses
OR
PO Doxycycline 100 mg bid x 28 days (penicillin allergy)
What are the possible regimens for a person with Neurosyphilis?
IV Crystalline penicillin G 3-4 million units q4h or 18-24 MU/d as continuous infusion x 10-14 days
OR
IM Procaine penicillin G 2.4 MU daily plus PO probenecid 500mg QDS x 10-14 days
OR
IV/IM Ceftriaxone 2g daily x 10-14 days (if penicillin allergy)
Define what is considered as treatment failure for syphilis and how to manage it
Defined as (at 6 months):
* Show sign and symptoms of disease or
* Failure to decrease VDRL or RPR titre by fourfold OR increase (e.g 1:16 to 1:64)
Management:
* Re-treat and re-evaluate for unrecognised neurosyphilis
State how you would monitor a patient with syphilis (no neurosyphillis)
Monitor for:
1) The Jarisch-Herxheimer reaction is an acute febrile reaction frequently accompanied by headache, myalgia, and other symptoms that usually occur within the first 24 hours after any therapy for syphilis.
2) Quantitative VDRL or RPR at 3, 6, 12, 18 and 24 months to measure response
o 6, 12 and 24 months are the key times
o Treatment success = decrease of VDRL or RPR titre by at least fourfold e.g. 1:64 to 1:16)
State how you would monitor a patient with neurosyphillis
Monitor for:
1) The Jarisch-Herxheimer reaction is an acute febrile reaction frequently accompanied by headache, myalgia, and other symptoms that usually occur within the first 24 hours after any therapy for syphilis.
2) Quantitative VDRL or RPR at 3, 6, 12, 18 and 24 months to measure response
o Treatment success = decrease of VDRL or RPR titre by at least fourfold e.g. 1:64 to 1:16)
3) Lumbar puncture (CSF examination) every 6 months until CSF normal
How would you manage sex partners of patient with Syphilis?
o All at risk sexual partners should be evaluated for STIs and treated if tested positive.
o Persons who receive syphilis treatment must abstain from sexual contact with new partners until the doctor says ok to resume.
What are the clinical symptoms of HSV?
o Classical painful multiple vesicular or ulcerative lesions (when vesicles burst)
o Also local itching, pain, tender inguinal lymphadenopathy
o Flu like symptoms (e.g., fever, headache, malaise) during first few days after appearance of lesions.
o Prodromal symptoms like mild burning, itching or tingling are seen in approximately 50% of patients prior to appearance of recurrent lesions (in recurrent disease).
o Symptoms less severe in recurrent disease (less lesions, heal faster, milder symptoms)
What are the diagnostic tests available for first episode of HSV?
- Viral cell culture (hard to do so not main diagnostic test)
- NAAT (PCR) for HSV DNA from genital lesions (main test)
What diagnostic tests are available for HSV (not first episode)
- Virologic Tests:
1) Viral cell culture (hard to do so not main diagnostic test)
2) NAAT (PCR) for HSV DNA from genital lesions (main test) - Type-specific serologic tests (HSV-1 or HSV-2)
What are the clinical effects of antiviral treatment of HSV?
o Reduce viral shedding
o Reduce duration of symptoms and
o Reduce time to healing of 1st episode
- Note: Does not prevent latency or affect frequency and severity of recurrent disease after drug is discontinued
State the possible antiviral regimens for first episode of herpes (assuming non-severe disease)
Acyclovir:
PO: 400mg TDS for 7-10 days
Valacyclovir:
PO 1g BD for 7-10 days (higher F so can give less freq compared to Acyclovir)
Duration of treatment can extend beyond 10 days if healing incomplete
State the possible antiviral regimen(s) for first episode of herpes (severe disease/ hospitalisation/ immunosuppressed)
IV Acyclovir: 5-10 mg/kg q8h x 2-7 days, followed by PO to complete a total 10 days therapy
What are the possible regimens for chronic suppressive therapy of HSV?
- PO Acyclovir 400mg BD
- PO Valacyclovir 500mg once daily*
o Might be less effective for patients with frequent recurrences (>10 per year) - PO Valacyclovir 1g once daily
o Preferred over 500mg regimen if > 10 recurrence per year
PO Famcyclovir 250mg BD also possible but not in SG
What are the possible regimens for episodic therapy of HSV?
- PO Acyclovir 800mg BD for 5 days
- PO Acyclovir 800mg TDS for 2 days
- PO Valacyclovir 500mg BD for 3 days
- PO Valacyclovir 1g once daily for 5 days
(In general, the less frequent the dosing, the longer the duration)
What are the pros and cons of chronic suppressive therapy for HSV?
Pros:
- Reduces the frequency of recurrences by 70%-80% in patients who have frequent recurrences (i.e. > 6 recurrences per year)
o no symptomatic outbreaks = improved quality of life
- Established long term safety & efficacy
- Decrease risk of transmission (in combination with consistent condom use and abstinence during recurrences)
Cons:
- cost
- compliance
What are the pros and cons of episodic therapy for HSV?
Pros:
* Shorten duration and severity of symptoms
* Less costly vs chronic suppression
* Patient more likely to be compliant
Cons:
* Requires initiation of therapy within 1 day of lesion onset or during the prodrome that precedes some outbreaks (start within 1 day for best effect)
* Does not reduce risk of transmission
How would you manage sex partners of someone with HSV?
o Symptomatic sex partners should be evaluated and treated in the same manner as patients who have genital lesions.
o 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. May be offered type specific serologic testing for HSV 2.
What are some supportive care measures for a person with HSV? (4)
1) Warm saline bath relieves discomfort
2) Symptoms management
* Analgesia, anti-itch (antihistamine)
3) Good genital hygiene to prevent superinfection
* Vesicle can break causing risk of superinfection
4) Counselling regarding natural history
What is the mode of transmission of HIV?
Through specific body fluids blood, semen, genital fluids, and breast milk
Which STI(s) can be transmitted via in utero pathway (i.e crosses the placenta)?
syphilis, HIV
Which STI(s) can be transmitted during childbirth?
Chlamydia, Gonorrhea, HSV, HIV
Which STI(s) can be transmitted through breastmilk?
HIV
What are the goals of ART in HIV? (5 total)
1) Reduce HIV associated morbidity and mortality
2) Prolong the duration and quality of survival
3) Restore and preserve immunologic function
4) Maximally and durably suppress plasma HIV viral load
Possible to suppress HIV viral load to undetectable levels in plasma which greatly decreases risk of transmission
5) Prevent HIV transmission
State the uses of CD4 count as a surrogate marker in HIV
- Most important laboratory indicator of immune function in HIV infected patients
- Also the strongest predictor of subsequent disease progression and survival
- Use to assess response to antiretroviral therapy
- Use to assess the need for initiating or discontinuing prophylaxis for opportunistic infections (e.g. prophylaxis for pneumocystis pneumonia is started when CD4 cells are <200 cells/mm3)
- Use to determine urgency for initiating antiretroviral therapy (not as much currently)
What is considered adequate CD4 response to HIV ART?
An increase in CD4 count in the range of 50 to 150 cells/mm^3 during the first year of therapy
State the uses of HIV Viral Load as a surrogate marker in HIV
Most important indicator of response to antiretroviral therapy and can be useful in predicting clinical progression
What are the benefits of early HIV treatment? (4 total)
1) Maintenance of a higher CD4 count and prevention of potentially irreversible damage to the immune system
2) Decreased risk for HIV associated complications that can sometimes occur at CD4 counts >350 cells/mm3, including tuberculosis, non-Hodgkin’s lymphoma, Kaposi’s sarcoma, peripheral neuropathy, and HIV associated cognitive impairment
3) Decreased risk of non-opportunistic conditions, including cardiovascular disease, renal disease, liver disease, and non-AIDS associated malignancies and infections
4) Decreased risk of HIV transmission to others, which will have positive public health implications
What are the limitations of starting HIV treatment early (6 total)
1) Development of treatment related side effects and toxicities (Less of concern with newer agents)
2) Development of drug resistance because of incomplete viral suppression (i.e non-adherence), resulting in loss of future treatment options
3) Transmission of drug resistant virus in patients who do not maintain full virologic suppression
* Hence even in ART naïve person, need to check resistance pattern before starting treatment in case they gain resistant HIV from partner)
4) Less time for the patient to learn about HIV and its treatment and less time to prepare for the need for adherence
5) Increased total time on medication, with greater chance of treatment fatigue
6) Increased cost
What are the names of the PK enhancers?
Ritonavir and Colbicistat
State the recommended combinations of ART for HIV naive patients
(assuming no high viral load or HBV coinfection)
2 NRTI + 1 INSTI:
1) Tenofovir + emtricitabine + bictegravir
2) Tenofovir + emtricitabine + dolutegravir
3) Abacavir + lamivudine + dolutegravir (3 in 1, Triumeq®)
1 NRTI + 1 INSTI:
1) Emtricitabine + dolutegravir
State when the 1 NRTI + 1 INSTI combination CANNOT be used
1) High viral load > 500,000 copies/mL
2) HBV coinfection
3) When ART is to be started before test results for resistant HIV strain or HBV are available
What are the names of the common NRTIs?
Tenofovir, Emtricitabine, Abacavir, Lamivudine, Zidovudine
Which NRTI has higher risk of mitochondrial toxicity (e.g lactic acidosis, hepatic steatosis, lipoatrophy)
Zidovudine
Which NRTI does not require dose adjustment in renal impairment
Abacavir
What NRTI is associated with hyperpigmentation?
Emtricitabine
Abacavir is contraindicated in what group of patients and why? (3 points)
1) Patients with HLA-B*5701 (potentially fatal hypersensitivity)
2) patients who develop hypersensitvity
3) patients with high CV risk (concern for MI)
What are the ADRs of Zidovudine?
1) GI
2) Bone marrow suppression leading to neutropenia or anemia
3) Myopathy
4) Lactic acidosis, hepatic steatosis, lipoatrophy (more common in Zido than the others)
What are the side effects of tenofovir?
1) N/V/D
2) renal impairment
3) decrease in bone mineral density (increase risk of osteoporosis and osteopenia)
Note: TAF < TDF (for Renal impairment and BMD decrease)
What are the names of the common INSTIs?
Bictegravir, Dolutegravir, Raltegravir, Elvitegravir
(-gravir)s
What are the common ADRs of INSTIs?
1) Weight gain, diarrhoea, nausea, headache.
2) Depression, and suicidality have rarely reported with INSTI use (primarily in patients with pre-existing psychiatric conditions)
What are the unique side effect(s) of Bictegravir and Dolutegravir?
Increase SCr (through inhibition of tubular secretion i.e NOT impairment of renal fn)
What are the unique side effect(s) Raltegravir?
1) Pyrexia (fever)
2) Creatinine kinase elevation (rhabdomyolysis)
Which INSTIs have higher genetic barrier to resistance?
Bictegravir, Dolutegravir
What are the DDIs of INSTIs?
1) Concurrent administration of polyvalent cations lowers bioavailability of INSTIs.
2) B, D and E are CYP3A4 substrates
What are the names of the commonly used NNRTIs?
Efavirenz, Rilpivirine
What are the side effects of NNRTIs? (5)
- Rash, SJS
- Neuropsychiatric SE (dizziness, depression insomnia, abnormal dreams, hallucination; the more serious Neuropsychiatric effects need to be monitored)
- Hyperlipidemia (increase in LDL C and triglycerides)
- Hepatotoxicity
- QT-prolonging
Note: Rilpivirine < Efavirenz for side effects
What is the indication for the use of Maraviroc?
Only in people whose strain of HIV uses the CCR5 receptor to enter the CD4 cells.
o Need co-receptor tropism assay before initiation -> check what is the receptor that HIV uses to enter the CD4 in the patient
o Must be CCR5 predominant to use maraviroc (not to use if CXCR4 or dual/mixed tropism)
What are the side effects of CCR5 antagonist? (9)
1) Abdominal pain,
2) cough,
3) dizziness,
4) musculoskeletal symptoms,
5) pyrexia,
6) rash,
7) upper respiratory tract infections (flu like symptoms),
8) hepatotoxicity,
9) orthostatic hypotension.
What are the DDI for CCR5?
CYP3A4 inducer/ inhibitor
What is the name of the fusion inhibitor that is used as ART?
Enfuviritide
What are the ADRs of Enfuviritide? (3)
1) Injection site reactions (e.g redness, induration, nodule/cyst, brusing)
2) Hypersensitivity (rare; fever, rash, chills, decreased BP)
3) Increased bacterial pneumonia (rare)
What are the names of the common Protease Inhibitors?
Ritonavir, Lopinavir, Atazanavir, Darunavir, Fosamprenavir
(-navir)s
What are the DDI of Efavirenz?
It is a CYP 3A4 substrate, CYP2B6 and 2C19 inducer
What are the DDI of Rilpivirine?
1) It is CYP 3A4 substrate,
2) oral absorption is reduced with increased gastric pH; use with PPIs is contraindicated
What are the class side effects of Protease inhibitors? (5 total)
- Metabolic complications (Dyslipidemia, insulin resistance)
- Gastrointestinal side effects (nausea, vomiting, diarrhoea)
- Liver toxicity (concern especially with chronic hepatitis B or C)
- Morphologic Complications: Fat maldistribution (Lipohypertrophy)
- Increased risk of osteopenia/ osteoporosis
Which class of ART is associated with Lipoatrophy?
NRTI
Which class of ART is associated with Lipohypertrophy?
Protease inhibitor
What are the unique side effects of Ritonavir?
o Paresthesia (numbness of extremities)
o Taste perversion
Which protease inhibitor(s) have less GI and lipid effects?
Azatanavir, Darunavir
What is/are the unique side effect(s) of Darunavir?
o Skin rash (10%), concern for SJS (it is a sulphonamide)
What are the unique side effects of Atazanavir?
o Hyperbilirubinemia
o QTc prolonging
o Skin rash
What is unique about the formulations of Protease Inhibitors?
o All are co-formulated with ritonavir or cobicistat – PK enhancers
What are potential DDIs for Protease inhibitors?
- They are CYP3A4 inhibitors and substrates
Ritonavir affect which CYP enzymes?
potent CYP3A4, 2D6 inhibitor
What DDI is unique to Atazanavir?
o Absorption decreases with increased pH (contraindicated with concurrent use of PPIs)
What is the normal range of CD4 count in a healthy person?
500-1200 cells/mm3
