HIV Flashcards
Who should be tested for HIV?
“everyone”
- People with risk factors: IVDU, MSM, sex workers, people with multiple partners, areas of high endemicity, rape victims, suggestive sx
- Mandated in blood donors, organ recipients/donors, military applicants, active duty, and sometimes newborns, pregnant women, inmates
What are office tests for HIV?
Gold standard: 4th generation HIV Ab/Ag test that can detect P24 (which appears more quickly in immune response)
Uses modified ELISA technology that tests for HIV1 and 2 and antibodies and P24 antigen
Usually serum test and needs no confirmation
Urine test: calypte for HIV 1 Ab only
What are at-home tests for HIV?
Oraquick, Insti HIV1/2 Serum, saliva Results in 20 minutes ELISA technology to detect Abs only Few are 4th gen, so you will need confirmation with serology
AIDS Law Project Act 148/Act 59
HIV test offered in “opt out” format so that pt is advised that an HIV test will be performed unless they specifically decline it
Written informed consent is not required for test, provider documents the patient’s consent/refusal
Negative results don’t need to be given in person
Why is testing for HIV a big deal?
15% of people in US are HIV+ and unaware
Undiagnosed patients account for majority of transmission
Who is affected the most by HIV?
67% are gay and bisexual men
-Diagnoses have increased in AA (4%) and in
Hispanic/Latino (14%)
9% are people who inject drugs (PWID), but rate has been declining
When does acute HIV infection occur?
Usually 2-4 weeks after infection
And, about 50-90% of pts have some sx of acute seroconversion syndrome
What are the manifestations of acute HIV infection?
Typically manifest in 3-10 weeks after primary infection
Common: fever, adenopathy, pharyngitis, rash, myalgias, diarrhea, headache, N/V, hepatosplenomegaly, weight loss, neuro sx
Rare: thrush, herpes zoster, opportunistic infections (most commonly PCP)
How do you diagnose acute HIV infection?
- ELISA (serum) test: but there is a window (2-4 weeks post/infection) where P antigen has not reached detectable levels yet…if you are suspicious, do the 4th gen serum test AND…
- HIV RNA PCR (“viral load”): actually measures the virus and can detect it w/in a couple days of infection
What is the HIV progression?
Primary infection
2-4 week incubation
Weeks 3-10: acute viral syndrome with wide dissemination of virus
10 weeks-up to 9 years: clinical latency where you may not see any sx
Constitutional sx
Opportunistic disease/s
Death
What are conditions associated with CD4 <500?
Candidiasis (oral thrush, vaginal candidiasis) Pneumococcal pneumonia Pulmonary tuberculosis Herpes zoster Kaposi sarcoma Cryptosporidiosis Oral hairy leukoplakia HIV-associated ITP
What are conditions associated with CD4 <200
clinically-defined AIDS
Pneumocystis jirovecii pneumonia (PCP)
Toxoplasmosis
Cryptococcal meningitis
Miliary or disseminated tuberculosis
What are conditions associated with CD4 <50?
Disseminated CMV
Disseminated Mycobacterium avium complex
Progressive multifocal leukoencephalopathy
HIV-associated wasting disease
Neuropathies, HIV associated encephalopathy
HIV-associated cancers (most common)
When is prophylaxis recommended for HIV patient?
When CD4<200 (AIDS), put patient on double-strength Bactrim QD
Can stop prophylaxis when CD4 count has been >200 for >6 months
When CD4<50, continue Bactrim QD
What are AIDS defining illnesses?
Candidiasis - Bronchi, trachea, lungs, Esophageal Coccidiomycosis, disseminated Cryptococcosis Cryptosporidiosis (>1mo) CMV disease - Disseminated, Retinitis HSV - Chronic ulcers >1mo, Bronchitis, pneumonitis, esophagitis Histoplasmosis, disseminated Isosporiasis, chronic (>1mo) MAI or M kansasii, disseminated Non-tuberculous mycobacteria, extrapulm Pneumocystis jirovecii pneumonia Recurrent pneumonia Salmonella septicemia (recurrent) Toxoplasmosis Tuberculosis of any site HIV Encephalopathy Cervical cancer, invasive Kaposi sarcoma Lymphoma - Burkitt’s, Immunoblastic, Primary CNS Lymphoid interstitial pneumonia or pulm. lymphoid hyperplasia complex Progressive multifocal leukoencephalopathy HIV wasting syndrome
What is the initial workup of an HIV+ patient?
HIV genotype/resistance testing CD4 count and viral load CBC with Diff CMP Fasting lipid profile Hepatitis A, B, and C serologies RPR, rectal, pharyngeal, urine or cervical GC/Chlamydia PCR Tuberculosis screening
What immunizations are recommended in HIV+?
Yearly influenza vaccine Pneumococcal vaccine Hepatitis A and B vaccination series TDaP Yearly PPD (or IGRA, eg Quantiferon Gold) Meningitis Shingrix (shingles) Gardasil
What labs are recommended for routine management of HIV+?
CBC, Panel 20, CD4, viral load, RPR: every 3 months (q6 months if stable and undetectable) STI screening (and HCV) Standard cancer screening recs: Annual Pap smear (rectal and cervical) Mammograms Colonoscopy at age 50 DEXA scan at age 50
Who should be treated for HIV?
EVERYONE should be treated immediately, regardless of CD4 count in order to decrease morbidity/mortality
What are the treatment options for HIV?
NRTIs Integrase Inhibitors NNRTIs Protease Inhibitors CCR5 Inhibitors Fusion Inhibitors
What are the most common NRTIs (Nucleoside Reverse Transcriptase Inhibitors) used to treat HIV?
Abacavir (Ziagen) Emtricitabine (Emtriva) Lamivudine (Epivir) Tenofovir (Viread) Zidovudine (Retrovir) Tenofovir alafenamide
What are the integrase inhibitors?
Raltegravir (Isentress)
Elvitegravir
Dolutegravir (Tivicay)
Bictegravir (Bictarvy)
These should be paired with NRTI
What are the most common NNRTIs?
Efavirenz (Sustiva)
Rilpivirine (Edurant)
Doravirine (Pifeltro)
What are the most common protease inhibitors?
Atazanavir (Reyataz)
Darunavir (Prezista)
Darunavir/cobicistat (Prezcobix)
Atazanavir/cobicistat (Evotaz)
Note: ritonavir and cobicistat have no action on their own, but are given in combination with other meds to boost action
What are fusion inhibitors?
NOT first line treatment
Enfuviritide (Fuzeon)
What are CCR5 Antagonists
NOT first line treatment
Maraviroc (Selzentry)
If pt’s virus is CCR5 (receptor) positive, can qualify to use this
What is the deal with Ritonavir (Norvir)?
It is technically a protease inhibitor, but it does not count as an active agent
Instead, it boosts other proteas inhibitors by increasing their serum levels w/o increasing toxicity
It is a CYP3A4 inhibitor
What is the deal with Cobicistat (Tybost)?
It is chemically similar to ritonavir
Boosts other medications, but with no inherent antiviral properties of its own
What are the first-line ARV regimens in naive patients?
Drug regimens usually consist of 2 NRTIs + integrase inhibitor
Dolutegravir/Abacavir/Lamivudine*
Dolutegravir + (TAF or Tenofovir)/Emtricitabine*
Elvitegravir/Cobicistat/Tenofovir/Emtricitabine
Elvitegravir/Cobicistat/TAF/Emtricitabine
Raltegravir + (TAF or Tenofovir)/Emtricitabine
**Dolutegravir (Tivicay) can increase neural tube defects, so currently shouldn’t be used in pts planning to become pregnant
What are the rules for prescribing ART?
People generally need THREE active agents
Almost everyone is started with 2 NRTIs as the backbone
Plus, either:
Integrase inhibitor OR
NNRTI OR
Boosted protease inhibitor (PI)
What are some considerations regarding prescribing Abacavir (which is a component of Triumeq and Epzicom)?
Must get genetic marker testing because of a potentially fatal reaction to Abacavir
What are some SE considerations with Reyataz?
Causes jaundice and realllly high bilirubin, but the hyperbilirubinemia is not clinically significant
But this is why it is not first line treatment
How do statins and ART interact?
Protease inhibitors increase statin levels
NNRTIs decrease statin levels
How does Warfarin and ART interact?
ARVs (NNRTIs and PIs) may increase OR decrease the INR (monitor)
How do PPIs & H2 blockers interact with ART?
PPIs/H2 blockers and subsequent acid suppression significantly DECREASES the absorption of Atazanavir or Rilpivirine, which seriously decreases the concentration of those ARTs
How do Trazodone and ART interact?
All protease inhibitors (e.g., ritonavir) increase trazodone AUC by up to 240%
How do Alprazolam and Diazepam and ART interact?
All protease inhibitors increase the AUC of benzos by up to 250%
Use instead: lorazepam, oxazepam, temazepam
How do phenytoin and ART interact?
PIs, NNRTIs, and CCR5As decrease serum levels of phenytoin
How do oral contraceptives and ART interact?
PIs and NNRTIs decrease levels of OC by 30-50%
How do sildenafil and ART interact?
PIs increase levels of sildenafil substantially
How do fluticasone (inhaled/intranasal) and ART interact?
PIs increase fluticasone and can precipitate Cushing’s syndrome
How do metformin and ART interact?
Dolutegravir increases metformin concentration
How do Fe and Ca and ART interact?
Must take with food or separate with dolutegravir
What is the exposure risk?
- 3% from needlestick injury (varies with hollow/closed bore, visible blood on needle, depth of injury, etc.)
- 09% from splash exposure
- 1-30% from sexual exposure
- 67% from needle sharing (single exposure)
Who needs PEP?
Health care workers after body fluid exposure
Victims of sexual assault
Other high risk exposures
When do you give PEP?
Ideally within 1 hour of exposure
MUST BE within 72 hours
Continued for 28 days
What agents are given in PEP?
(If you know the HIV+ person’s resistance profile, choose 3 agents you know their virus is susceptible to)
Otherwise, standard regimen is 28 days of:
- Tenofovir/Emtricitabine (Truvada)
- Raltegravir (Isentress) or Dolutegravir (Tivicay)
ONLY one occupational exposure seroconversion since 1999
What is PrEP?
Involves chemoprophylaxis of high risk individuals
Once daily Truvada 300 mg for HIV- persons to prevent HIV infection
Who is a candidate for PrEP?
MSM: HIV+ partner, recent bacterial STI, high # sex partners, inconsistent/no condom use, commercial sex work
Heterosexual: HIV+ partner, recent bacterial STI, high # sex partners, inconsistent/no condom use, commercial sex work, in high-prevalence area/network
Injection drug users: HIV+ injecting partner, sharing injection equipment, recent drug tx (but currently injecting)
Who is clinically eligible for PrEP?
MUST BE:
- HIV negative before starting PrEP
- No s/sx of acute HIV
- Normal renal function
- No contraindicated meds
- Documented HBV and vaccination status (since Truvada is active against HBV)
Why is Truvada used in PrEP?
- High genetic barrier to resistance
- Good tissue penetration
What are SE of Truvada?
Nausea, flatulence, rash, headache
Adverse events: Decreased bone mineral density (13%) Headache (7%) Weight loss (3%) Abdominal pain (4%) Abnormal phosphorus levels (<2.0 mg/dL: 10%), decreased neutrophils (5%) Bone fracture (2%) <1%: Glycosuria, immune reconstitution syndrome, proteinuria
How often do you follow up with HIV+ patient?
At least every 3 months to do the following:
- HIV test, med adherence counseling, behavioral risk reduction support, SE assessment, STI sx assessment
- Every 3 and 6 months to assess renal function
- Every 6 months test for STIs
- Assess pregnancy/intent to get pregnant every 3 mos
- Access to clean needles/syringes and drug treatment services
When can you stop PrEP in sero-discordant partners?
- When ending sexual activity with HIV+ partner
- If HIV-infected partner initiating ART
(PrEP may be a time-limited “bridge” to ART initiation in couples)
What is the prevalence of HSV?
-Recurrent, lifelong infection
50% (or more) of new cases are asymptomatic or unrecognized
-22% of adults 12+ have HSV-2 antibodies
How is HSV2 transmitted?
Sexually and perinatally
Most sexual transmission occurs when source is asymptomatic
Greater from men to women than women to men
Likelihood of transmission declines with increased duration of infection
Up to 90% of people who are seropositive for HSV2 Ab have NO clinical hx of anogenital herpes outbreaks
How are HSV2 and HIV related?
HSV2 infection facilitates the acquisition and transmission of HIV!!
What does the first episode of primary HSV-2 infection look like?
- Multiple lesions that are more severe, last longer, and have higher titers of virus than recurrent infections (11-12 days)
- Lesions progress from papules to vesicles to pustules to coalescing ulcers to crusts to healed
- Lasts for 2-4 weeks
- Often systemic sx: fever, HA, malaise, myalgia
- Local sx: pain, itching, dysuria, vaginal/urethral discharge, tender inguinal adenopathy
- HSV cervicitis in ~90%
What does a recurrent infection of HSV-2 look like?
- Prodromal sx that begin 12-24 hrs before lesions: localized tingling and irritation (in 50%)
- Illness lasts only 5-10 days with sx that are less severe than primary infection and no systemic sx
- HSV-2 is more prone to recur than HSV-1
- HIV+ pts may have prolonged, severe, or atypical episodes of genital, perianal, or oral herpes
What is the treatment for HSV-2?
Treat ALL initial infections to decrease sx!
Options:
- Acyclovir (cheapest)
- Valacyclovir (fewer pills)
- Famcicyclovir
Dose and duration depends on indication, initial infection, recurrent infection, suppression, and HIV status
Note: may treat a pt whose culture did not come back positive because the virus sheds cyclically, so use judgment
What causes syphilis?
Treponema pallidum: corkscrew-shaped, motile micraerophilic bacterium
Cannot be cultured in vitro
Cannot be viewed by normal light microscopy
How is T. pallidum (syphilis) transmitted?
- Direct contact with infectious lesion during sex (open lesions, like primary chancres, are very infectious) or condyloma lata and mucus patches
- Vertical transmission through placenta
- Blood transfusion (RARE)
What are characteristics of primary syphilis?
- Primary lesion (chancre) develops at site of inoculation
- Chancre progresses from macule to papule to ulcer; typically painless, raised + indurated, with clean base; it is HIGHLY infectious and heals spontaneously in 1-6 weeks. 25% of patients will have multiple lesions
- Regional lymphadenopathy that are rubbery, painless, bilateral
- Serologic tests for syphilis Abs may be negative during early primary syphilis!!!
What are characteristics of secondary syphilis?
- Secondary lesions occur 3-6 weeks after the primary chancre appears and can persist for weeks to months
- Primary and secondary stages may overlap
- Serologic tests are at their HIGHEST titers at this time!
- Systemic sx: fatigue, malaise
Classic Sx: Rash (palms and soles of feet) Lymphadenopathy Mucous patches (lips or inside mouth) Alopecia Condyloma lata (flat wart things)
What are characteristics of latent syphilis?
- The host has suppressed the infection enough that no lesions are clinically apparent
- Only evidence: positive serologic test for syphilis
- May occur BETWEEN primary and secondary stages, between secondary relapses, and after secondary stage
- Early latent = <1 year duration
- Late latent = >1 year duration
***Cannot transmit syphilis when you are latent
What is neurosyphilis?
EARLY neurosphylis:
-Occurs a few months to a few years after infection and may involve acute syphilitic meningitis or ocular involvement
LATE neurosyphilis:
-Occurs decades after infection (rare) and may involve general paresis, tabes dorsalis, meningovascular syphilis, and ocular/otic involvement
What are characteristics of tertiary (late) syphilis?
- Approximately 30% of untreated pts progress to this within 1-20 years
- It is rare because of ABX!
- Manifestations: gummatous lesions, CV syphilis (aneurysms, valve ring dilation)
How do you diagnose syphilis?
- Based on the clinical sx
- If you suspect they have it, treat empirically because screening test may be negative for 2-4 weeks!
What are lab and serologic tests in syphilis?
Lab: Darkfield microscopy for primary syphilis
Serologic tests:
-Non-Treponemal = VDRL, RPR: for initial screening and then the lab will reflex the test for a specific antibody:
-Treponemal = TP-PA, FTA-ABS: for confirmation
What is the treatment of syphilis?
Primary: Benzathine Penicillin G 2.4 million units IM
Secondary: Same
Early Latent: Same
Late Latent/Latent of unknown duration: Benzathine PCN G 7.2 million units TOTAL, administered in 3 doses of 2.4 million units each, IM at 1-week intervals
What is the treatment of neurosyphilis?
Aqueous crystalline PCN G 18-24 mill units/day, administered as 3-4 million units IV Q4hrs or continuous IV infusion, for 10-14 days
After PCN infusion, Bicillin 2.4 mill units
How do you treat syphilis in PCN allergy?
Early: doxy 100 mg BID x 14 days (or tetracyclin 500 mg QID x14 days OR azithromycin 2gm once)
Early latent: Same
Late latent: doxy 100 mg BID x 28 days or tetracycline 500 mg QID x 28 days
Pregnancy-desensitized and treat with PCN
Monitoring of syphilis:
Jarisch-Herxheimer reaction
Acute, self limited febrile reaction within first 24 hours
Occurs in 10-35%
HA, myalgias, rigors, diaphoresis, hypotension and rash
Lasts 12-24 hours
Use NSAIDs
Monitoring during tx of early syphilis vs. late syphilis (serology)
Early syphilis
4 fold decline over 6-12 months
Ie. 1:32 to 1:8
Some may remain seropositive, usually <1:8
Late syphilis
4 fold decline over 6-24 months
What causes gonorrhea?
Neiserria gonorrhoeae (gram negative)
What can gonorrhea infect?
Oral, urethral, vaginal, anal
What are sx of gonorrhea?
Can be asx (esp women)
Yellow, thick, profuse discharge (urtheral or anal)
Pharyngitis in high risk populations (tonsils w/ exudates)
Can present at PID or disseminated
What are sx of disseminated gonococcal infection?
Fever Hemorrhagic skin lesions Tenosynovitis Polyarthralgias Septic arthritis (30-40%)
How do you diagnose gonorrhea?
- Gram stain and culture
- NAAT (nucleic acid test) of urine, pharyngeal/rectal/cervical swab
(And test for chlamydia too!!)
How do you treat gonorrhea?
Ceftriaxone 250 mg IM PLUS Azithromycine 1 g once
This also treats empirically for Chlamydia…these STIs go hand in hand
What are chlamydia rates?
Number one STI
AND number one cause of non-gonococcal urethritis
What’s the organism with chlamydia?
Chlamydia trachomatis
Responsible for most bacterial STIs in men and women
Sexual or vertical transmission
What are the sx of chlamydia in men?
May be asx (up to 40%)
Urethritis
Urethral rectal pruritis, possible dysuria or tenesmus
What are the sx of chlamydia in women?
Commonly asx (70-90%) Urethritis/cervicitis/dysuria or PID
Recommend to screen all women <25yr and women at “increased risk” because of asx
What is cervicitis?
Caused by C. trachomatis
Majority of women are asymptomatic (70-80%)
Local signs of infection include: mucopurulent endocervical discharge, edematous cervical ectopy w/ erythema and friability
What is a C. trachomatis urethritis infection like in women?
Usually asx
s/sx include: dysuria, frequency, pyuria
What can C. trachomatis cause in men?
Conjunctivitis
Urethritis
Prostatitis
Complications? Reiter’s syndrome, epididymitis
Sequelae? chronic arthritis, infertility
What can C. trachomatis cause in women?
Conjunctivitis, urethritis, cervicitis, proctitis
Complications?? Endometiritis, salpingitis, Perihepatitis, Reiter’s
Sequelae? infertility, ectopic pregnancy, chronic pelvic pain, chronic arthritis
How do you diagnose chlamydia?
NAAT (nucleic acid amplification test)
Can test urine, rectal/cervical/pharnygeal swab
What is the treatment of chlamydia?
Azithromycin 1 g PO x1
OR
Doxycycline 100 mg BID x 7 days (NOT gold standard)
What’s mycoplasma genitalium?
No routine testing for it
Indicated in urethritis and cervicitis (becoming more frequent)
Urethritis, burning, discharge
How do you treat mycoplasma genitalium?
Azithromycin 1 g x once (80% cure rate)
OR
moxifloxacin 400 mg daily for 7-14 days
STI Key Points
Test with GC/CT urine/throat/rectal swab, RPR, HCV antibody with reflect to viral load, HIV
Always treat empirically if you clinically suspect STI
Treat partner with partner packs
