Unit 3- STIs, HIV, OIs, and Fungal Infections

STI Risk Factors

Unprotected sex, new/multiple partners, previous STI or partner with Hx of STI, MSM, Sex for money, Females < 25 yo, Men < 25 yo (chlamydia), incarceration, low SE status

How are STIs transmitted?

through mucosal contact with pathogen

Pathogens Responsible for STIs

N. gonorrhoeae, C. trachomatis, T. vaginalis

Screening recommendations for Chlamydia and gonorrhea for sexually active women under 25 and women over 25 at elevated risk

Annually

Screening recommendations for Chlamydia and gonorrhea for pregnant women

annually for all less than 25 yo, retest during 3rd trimester too

Screening recommendations for Chlamydia and gonorrhea for MSM

annual or every 3-6 months if at increased risk

Screening recommendations for Chlamydia and gonorrhea for Persons with HIV

At first HIV eval and annually thereafter

Screening recommendations for trichomonas for sexually active women under 25 and women over 25 at elevated risk

Annually if at elevated risk regardless of age

Screening recommendations for trichomonas for pregnant women

Recommended for all pregant women

Screening recommendations for trichomonas for MSM

low prevalence, less guidance

Screening recommendations for trichomonas for Persons with HIV

If sexually active female, at first HIV eval then annually thereafter

Symptoms of STIs

cervical/urethral discharge, vaginal pruritus, dysuria/urinary frequency, intermenstrual bleeding, rectal pain/bleeding/discharge, pharyngitis, conjunctivitis

How do we diagnose STIs

NAAT test, urine sample for men

Gonorrhea causative pathogen

Neisseria gonorrhoeae

Clinical presentation of gonorrhea

white, yellow, or green profuse urethral discharge common in men, cervical infection most common in women (most asymptomatic)

Potential consequences of gonorrhea and chlamydia in women

PID increases ectopic pregnancy and infertility risk, infant can have conjunctivitis

Treatment for Gonorrhea

IV Ceftriaxone (500 mg if < 150 kg; 1 g if higher)

Treatment for Gonorrhea if chlamydia not excluded

Ceftriaxone plus Doxy

Pathogen that causes chlamydia

Chlamydia trachomatis

Clinical presentation of chlamydia

mostly asymptomatic, minimal non-purulent discharge in men

Treatment for chlamydia

Doxycycline 100 mg BID x 7 days, can do 200 mg once if adherence concerns

Treatment for chlamydia in preganancy

Azithromycin 1 g PO once

Causative pathogen in Trichomoniasis

Trichomonas vaginalis

Clinical presentation of Trichomoniasis

vaginal erythema, irritation, and diffuse/malodorous green-yellow discharge, asymptomatic in men typically

Treatment for Trichomoniasis in females

Metronidazole 500 mg PO BID x 7 days

Treatment for Trichomoniasis in males

Metronidazole 2 g PO once

STI treatment goals

Resolution of Sx, Prevention of transmission, recurrent infection, and complications

STI follow-up recommendations

Repeat screening 3 months after treatment

How we reduce STI transmission

Screen for all sexual partners 60 days before infection or the most recent partner if more than 60 days since last encounter, PEP with Doxycycline within 72 hrs of sex

Infective pathogens for HSV

HSV-1 and HSV-2

What is unique about herpes virus in terms of its infection characteristics?

it can set up latent or persistent infection following primary infection

Drug targets for HSV

DNA-dependent DNA polymerase; thymidine kinase (required for drug activation)

HSV-1 also known as?

oral herpes

HSV-2 also known as?

genital herpes

How does HSV establish latency?

during initial infection, virus can travel up nerve and transcribe LAT section, then some external event can trigger the infection again

S/SX of HSV influenced by:

previous exposure, type of virus, age of host and immune function

HSV first episode primary classification

initial genital infection lacking antibodies to HSV-1 or 2

HSV first episode non-primary classification

initial genital infection with clinical or serologic evidence of prior infection

HSV recurrent classification

appearance of genital lesions at some time following healing of first episode infection

First episode HSV S/Sx

flu-like symptoms, multiple painful pustular lesions on genitalia, local itching, pain, discomfort, discharge, tender inguinal adenopathy

Recurrent episode HS S/Sx

fewer lesions, shorter duration, milder Sx overall

How do we diagnose HSV?

Lab tests (culture, serology, or PCR); can make presumptive Dx based on lesions and Hx of similar lesions

Drugs used for treatment of HSV

Acyclovir, Valacyclovir, Famciclovir

Which drug option for HSV has highest oral bioavailability?

valacyclovir and famciclovir

ADME for HSV drugs

topicals have low absorption, wide distribution, no human metabolism, primarily excreted renally

ADRs of HSV drugs

N/D/V, rash, renal toxicity (decreased with hydration), dizziness, pruritus, headache, CNS disturbance

Typical length of therapy for HSV

7-10 days for first infections, less if recurrent

HIV life cycle steps

Binding, Fusion, Reverse transcription, integration, replication, assembly, budding

What kind of cells does HIV infect

CD4 cells only: T-cells and macrophages

Types of HIV virus and where are they prevalent

HIV-1 (worldwide), HIV-2 (West Africa)

Transmission routes of HIV

unprotected sex, sharing needles/syringes, vertical transmission, contaminated blood products (rare in US)

Populations at risk of HIV infection

MSM, bisexual men, IV drug users, unprotected sex with multiple partners, rates higher in blacks and hispanics

Difference b/w HIV and AIDS

HIV is the virus, AIDS is the late stages of HIV infection

Goal of HIV therapy and general amount of drugs

suppress viral replication as much as possible for as long as possible; usually given 3 drugs, 2 in some cases

Targets/drugs for HIV therapy

Reverse transcriptase inhibitors(nucleoside and non-nucleoside), Protease inhibitors, Integrase inhibitors, Capsid inhibitors

NRTIs drug examples

lamivudine, abacavir, tenofovir disoproxil, tenofovir alafenamide, emtricitabine

NRTIs MOA

nucleoside analogues that bind to RT site to stop chain growth

How are NRTIs activated

phosphorylation by cellular enzymes

NRTIs ADRs

renal toxicity, bone density changes, dyslipidemia, deadly HSR with abacavir if gene present

NNRTIs MOA

chain terminator that binds allosterically to RT to slow down transcribing

NNRTIs drug examples

erfavirenz, etravirine, rilpivirine, doravirine

NNRTIs ADRs

mild GI, vivid dreams, depression, insomnia, weight gain

NNRTIs are cleared by and interact with what CYP?

hepatically, interact with CYP3A4

PIs MOA

binds to active site of protease and competes with substrates, preventing HIV protein splicing

PIs drug examples

Atazanavir, Darunavir

PIs ADRs

crystalluria, increased CKD risk, increased CVD events

INSTIs MOA

blocks cDNA strand transfer into host DNA by chelating metals in integrase active site

INSTIs drug examples

Bictegravir, Dolutegravir, Cabotegravir

INSTIs ADRs

insomnia, depression, dyslipidemia, weight gain

Lenacapevir class and MOA

capsid inhibitor that binds to p24 protein to prevent capsid assembly

How do we diagnose HIV?

test shows presence of HIV antigen or antibody

How do we diagnose AIDS?

CD4 levels less than 200 at any time or patient has AIDS defining illness

HIV screening recommendations

at least once for all pts aged 13-64, all pregnant patients at prenatal appt and again in 3rd trimester, those with risk factors test at least annually

S/SX of acute HIV infection and when they typically occur

sore throat, fever, chills, lymphadenopathy, muscle aches, fatigue (very non-specific); occur 2-4 weeks after infection

Possible Sx of chronic HIV infection

unexplained WL, diarrhea, peripheral neuropathy, candidiasis, cervical dysplasia

Food/drug interactions for NRTIs

minimal

Food/drug interactions for NNRTIs

Rilpvirine and Etravirine need to be taken with food

Food/drug interactions with PIs

take with food for increased bioavailability

Food/drug interactions for INSTIs

No requirements for taking with food

Which ARV drugs are CI with PPIs

Rilpivirine and Atazanavir

Which class of ARVs undergo chelation with metals?

INSTIs

Metabolism considerations with NNRTIs

CYP3A4 substrates

Metabolism considerations with PIs

CYP3A4 inhibitors and P-GP DDIs

Metabolism considerations with INSTIs

UGTA1 interactions

Elimination of ARVs

NRTIs renal except for TAF, rest are fecal

PK enhancers in HIV and why we use them

Ritonavir and cobicistat, CYP3A4 inhibitors used to boost other PIs

ARV Drugs with high barrier to resistance

NRTIS, PIs, Dolutegravir and Bictegravir

ARV drugs with low barrier to resistance

NNRTIs, Raltegrevir and Elvitegravir

First-line ARV for HIV

INSTI plus 2 NRTIS; Bictegravir/TAF/emtricitabine, Dolutegravir plus tenofovir/emtricitabine

Laboratory goals for efficacy in HIV treatment

undetectable viral loag (<20-75 copies/mL), and then increased CD4 count

Which ARV requires allelle testing and what allele?

abacavir and HLA-B*5701

Should resistance testing be performed for all HIV patients?

YES

Safety monitoring for HIV treatment

Electrolytes, LFTs, Lipids, FBG/A1C, CBC

HIV pts with CD4 less than 200 at risk for what OI?

PJP

HIV pts with CD4 less than 100 at risk for what OIs?

PJP and toxoplamosis

HIV pts with CD4 levels less than 50 at risk for what OIs?

PJP, toxoplasmosis, MAC, and cryptococcal meningitis

ARV that can also treat HBV infections

LET it B; lamuvidine, emtricitabine, tenofovir

IRIS definition and risk factors

fever and worsening OI in first few weeks of ART; CD4 <50 and high antigenic burden

PJP risk factors

CD4 <200, high plasma HIV-RNA, oral thrush, recent bacterial pneumonia, prior PJP

Sx of PJP

fever, progressive dyspnea, non-productive cough, chest discomfort