Flashcards in HIV Deck (76):
What type of cells are the target of HIV infection?
T cells with CD-4 and CCR5 receptors, macrophages/monocytes
How does HIV utilize a cells machinery to replicate?
After binding CD4 or CCR5 receptors on a cell surface, viral RNA is transcribed into DNA using the cell’s reverse transcriptase. The DNA is then integrated into the infected cell’s genome.
Pathophysiology of HIV
HIV primarily infects T lymphocytes that express the CD4 antigen, resulting in a progressive loss of these cells and impairment of cellular immunity as well as humoral immunity. When CD4 lymphocytes are sufficiently depleted there is the progression to AIDS, characterized by the development of opportunistic infections and malignancies.
How rapidly does HIV replicate?
Infected CD4 population doubles every 15 days.
While HIV1 is the most common strain of HIV seen in the US, where is HIV2 most commonly seen?
How does HIV2 differ from HIV1?
HIV2 is less virulent but more indolent, with decreased transmission rates
How quickly can HIV be detected after a primary infection?
How common are symptoms during the acute phase?
40-90% have symptoms within 2w of exposure
What are the primary symptoms with acute HIV?
Fever, LAD, pharyngitis, rash, and myalgias/arthralgias
Following the acute infection, what is the typical latency period before symptoms develop?
What is the typical rate of CD4 drop/year during the latency period?
Diagnosis of HIV
Screening ELISA is positive and is followed by a confirmatory positive Western blot.
When is rapid testing for HIV indicated?
Previously untested women presenting in labor, or those expected to be delivered for maternal or fetal indications before results of conventional testing can be obtained.
Sensitivity & specificity, PPV of rapid HIV testing
The sensitivity and specificity of each of the available rapid testing assays ranges from 95% to 100%, while the positive predictive value depends on the prevalence of disease in the population. In a population with low prevalence of disease, the positive predictive value is low while the false- positive rate is high. For example, with a prevalence of disease of *1% in the population, the positive predictive value of the test may be as low as 60%.
What should be done if a rapid HIV test is positive?
ARV prophylaxis should be offered without waiting for the results of the confirmatory conventional tests.
How does viral load affect transmission rates?
27% with VL >100,000, <20
Diagnosis of AIDS
Regardless of symptoms, a CD4 <200 cells/mm3 or the presence of an AIDS-defining illness in an HIV-positive person is an AIDS diagnosis.
What is the recommended approach to HIV screening in pregnancy? Opt-in or opt-out?
An opt-out approach has been shown to increase acceptance rates for HIV testing in pregnant women and is the recommended approach to universal prenatal screening.
After initial prenatal testing for HIV, who should have a repeat test? When?
28-32 wksHigh-risk behaviorHigh-prevalence areaPreviously declined testing
Risk factors for perinatal HIV transmission
Closely related to viral load at the time of delivery. Other risk factors: Low CD4+ T-lymphocyte countLack of ARV therapyBiologic phenotype of the virusSubstance abuseProlonged duration of membrane ruptureHCV coinfectionSexually transmitted infections (STIs)Preterm birthChorioamnionitis
Fetal complications of HIV
Possible increased risk of preterm delivery if on a protease inhibitor (PI) containing regimen, but no increased risk of FGR, stillbirth, or low Apgar scores.
Effect of pregnancy on HIV progression
Pregnancy has no clear effect on HIV progression. A transient but clinically insignificant decrease in the CD4+ T-lymphocyte count has been described.
Antepartum perinatal HIV transmission risk
Intrapartum perinatal HIV transmission risk
Postpartum breastfeeding transmission risk
Transmission rate of HIV without ART
Transmission rate of HIV on AZT monotherapy
Transmission rate of HIV with ART
If you had only intrapartum AZT and C/S available, what would be the transmission rates?
5-8% with ZDV, 2% with C/S + ZDV
What is the transmission rate once SROM has occurred?
Is there still a benefit of C/S once labor/SROM occurs?
The benefit is lessened significantly, so give loading dose of AZT and proceed with C/S
HIV Stage A1
(Used by UCH CHIP team)Asymptomatic, acute, primary HIV, or PGL (persistent generalized lymphadenopathy)CD4 >/= 500/uL
HIV Stage A2
Asymptomatic, acute, primary HIV, or PGLCD4 200-499/uL
HIV Stage A3
Asymptomatic, acute, primary HIV, or PGLCD4 =200/uL (AIDS indicator)
HIV Stage B1
Symptomatic, not A or C conditionsCD4 >/= 500/uL
HIV Stage B2
Symptomatic, not A or C conditionsCD4 200-499/uL
HIV Stage B3
Symptomatic, not A or C conditionsCD4 =200/uL (AIDS indicator)
HIV Stage C1
AIDS-indicator conditionsCD4 >/= 500/uL
HIV Stage C2
AIDS-indicator conditionsCD4 200-499/uL
HIV Stage C3
AIDS-indicator conditionsCD4 =200/uL (AIDS indicator)
Preconception counseling for HIV+ women
-Initiate or modify ART, avoiding potentially teratogenic agents-Opportunistic infection prophylaxis as indicated by CD4 count-Appropriate immunizations-Optimize maternal nutritional status, initiating folic acid supplementation-Screen for and treat STIs-Screen for psychological and substance abuse disorders Advise how to optimize the chance of conception while minimizing the risk of sexual transmission-Prevent unwanted pregnancies
Initial prenatal visit for HIV+ patients - H&P
-Complete medical/obstetric/gynecologic-History of prior or current ARV use-Symptoms of AIDS - fever, night sweats, weight loss, a new persistent dry cough, diarrhea, refractory vaginal candidiasis, oral candidiasis, new outbreaks of herpes.-Assess need for prophylaxis against opportunistic infections such as Pneumocystis pneumonia (PCP) or Mycobacterium avium complex (MAC).-Complete physical exam, if CD4 <200 cells/mm3, specifically evaluate for thrush, HSV, lymphadenopathy, or a rash.Discuss risk of transmission and factors that modify those risks.Discuss risk and benefits of ART for both the patient and the fetus.Educate on safe sex practices with condoms.
Initial prenatal visit for HIV+ patients - Labs
-HBsAg, HBsAb, HBcAb, HCV ab -CMV and Toxo antiboides-CBC w/ diff, LFTs, Cr, ur protein-VDRL/RPR, gc/ct-PPD.-Early 1 hr gtt if prolonged protease inhibitor (PI) exposure.-Pap smear-CD4 cell count-Plasma HIV RNA level-Resistance testing: before starting ART, if initial HIV RNA level above the threshold for resistance testing on tx-Genotyping is preferable to phenotyping because it is less expensive, it has a faster turnaround time, and a greater sensitivity for detecting mixtures of wild-type and resistant virus.-HLA B-5701 testing if abacavir use is anticipated.
PPD testing if CD4 < 200 cells/mm3
A negative test may be the result of anergy, and pts should have a CXR to r/o tb
Monitoring HIV during pregnancy
-Q trimester: CBC w/ diff, LFTs, Cr, ur protein-CD4 cell count - at least q 3 mos-Plasma HIV RNA levels - 2 to 4 weeks after initiating/changing therapy, q mo until HIV RNA levels are undetectable, and then at 34-36w to determine mode of delivery-VL should decrease by 1 to 2 logs within 4 weeks of starting therapy.-Resistance testing: if suboptimal viral suppression after ARV initiation, if persistently detectable plasma VL on therapy which previously suppressed the virus to undetectable
Delivery recommendations for pregnant women w/ HIV
l Women with a viral load >1000 copies/mL should becounseled regarding the benefit of planned cesarean delivery at 38 weeks to reduce the risk of transmission. With effective antiretroviral therapy leading to undetectable viral load, planned cesarean delivery for viral load >1000, and formula feeding, the risk of perinatal transmission is reduced to <2%.
AZT treatment for newborn
The newborn should receive AZT for at least the first four to six weeks of life (dose 2 mg/kg qid).
Dx of HIV in the infant
May take up to 18 mos to clear maternal antibodies, thus a qualitative HIV-1 DNA PCR assay is usedShould be performed at a minimum age of 14-21 days, at 1-2 mos, and at 4-6 mosHIV may be excluded with 2 or more negative tests, w/ one at >14 d and >1 mo.Many confirm w/ an HIV antibody test at 12-18 mos.
After birth, how long should a neonate be treated with ART?
Which pts receive ART in pregnancy?
-If newly diagnosed in 1st trimester, & pt does not meet guidelines to start ARV therapy for herself, then defer tx until 14w to decr embryopathy risk. -If pt presents and is already on ARV, then co ntinue tx (d/c teratogenic agents)-Continue ARV tx for duration of pregnancy to decr vertical txmission.-Should start tx by 28w to achieve undetectable VL prior to delivery
How common is ART resistance?
Which women should receive AZT during pregnancy (before labor)?
-Women who present before labor, and not already on ARV tx, should be started on a HAART regimen that includes AZT-If a woman already on ARV tx presents less than 36w, then continue HAART and include AZT, even if resistant
Guidelines for selecting an ART regimen in pregnancy
-At least one nucleoside reverse transcriptase inhibitor (NRTI) with high placental transfer (zidovudine/lamivudine/stavudine/tenofovir/abacavir) should be included if possible.-AZT should be part of the regimen in all pregnant women unless contraindicated: antepartum AZT orally 300 mg bid from week 14 until delivery -AZT can cause anemia and neutropenia, so monitor CBC.
AZT dosing in labor
Intrapartum infusion of AZT IV 2 mg/kg over the first hour followed by a continuous infusion of 1 mg/kg/hr until delivery.
ARV medications/combinations to avoid
Efavirenz, hydroxyurea, amprenavir solution, combinations of AZT with d4T or d4T with ddI.
Side effects of AZT
Hemoglobin < 8 g/dLAbsolute neutrophil count < 750 cells/mm3AST or ALT > 5x nlRarely linked to mitochondrial toxicity in neonates
Side effects of protease inhibitors
Hyperglycemia (new-onset DM, exacerbation of existing DM, DKA)
Side effects of non-nucleoside reverse transcriptase inhibitors
(Nevirapine)RashHepatotoxicityRisk higher if CD4 > 250 cells/mm3Monitor transaminases, esp in first 18w of tx
Are there any teratogenic ARV agents?
Efavirenz - increased NTDs in animal studies
Antiretroviral tx in pregnancy - recommended agents
NRTI - Zidovudine (AZT, aka Retrovir) + Lamivudine (3TC, aka Epivir)) = CombivirNNRTI - Nevirapine (aka Viramune)PI - Lopinavir/ritonavir (aka Kaletra)
Antiretroviral tx in pregnancy - alternate agents
NRTI - Didanosine (ddI, aka Videx), Emtricitabine (aka Emtriva), Stavudine (d4T, aka Zerit), Abacavir (aka Ziagen)[fatal lactic acidosis has occured w/ ddI+D4T, use only if no other alternative]PI - Indinavir (Crixivan, requires boosting with ritonavir); Nelfinavir (Viricept), Atazanavir (Reyataz), Saquinavir (Invirase)
Antiretroviral tx in pregnancy - use in special circumstances
NRTI - Tenofovir (Viread, limited studies in preg, bone demineralization w/ chronic use)NNRTI - Efavirenz (Sustiva, CNS defects, avoid in 1st trim)PI - Amprenavir, Fosamprenavir - no studies in human pregnancy
Which ARV should be used in HBV+ pts?
Which uterotonic should be avoided due to the risk for protease inhibitor p450 interaction?
Vaccines in HIV+ pts
PneumovaxHepatitis BInfluenzaHepatitis A if HCV+TetanusDiptheriaInactivated polio if at riskRubella PP if CD4 > 200Varicella - being evaluated, not currently recommendedBCG - should not be administered
Pneumocystis jiroveci pneumoniaToxoplasmic encephalitisDisseminated Mycobacterium avium complexMycobacterium tuberculosisVaricella zoster virusCandidiasisNon-Hodgkin lymphoma
PCP pneumonia - indications for prophylaxis and first line drug
CD4 count <14History of AIDS-defining illnessHistory of oropharyngeal candidiasisHistory of PCP pneumonia (secondary prophylaxis)Trimethoprim-sulfamethoxazole(TMP-SMZ) one DS tablet daily
Disseminated MAC - indications for prophylaxis and first line tx
CD4 < 50 cells/uLAzithromycin 1200 mg PO/wk
Toxoplasmic encephalitis - indications for prophylaxis and first line tx
CD4 < 100 cells/uLSeropositive for T. gondii IgGTMP-SMZ one DS tab daily
Mycobacterium tuberculosis - indications for prophylaxis and first line tx
PPD >/= 5mm ORPrior + PPD w/o adequate tx ORContact with person with active TBregardless of PPD statusINH sensitive:INH 300 mg po + pyridoxine 50 mg po daily x 9 mo ORINH 900 mg po + pyridoxine 100 mg po 2x/w x 9 moINH resistant:Rifampin 600 mg po daily ORrifabutin 300 mg po daily x 4 mo
Varicella zoster - indications for prophylaxis and first line tx
Varicella nonimmune and exposed tochickenpox or shinglesVaricella Zoster immune globulin—5 vials (1.25 mL each) within 48–96 hours ofexposure
Cryptococcus - indications for prophylaxis and first line tx
CD4 < 50/mm3Fluconazole 150 mg PO daily
HSV - indications for prophylaxis and first line tx
Recurrent outbreaksAcyclovir 400 mg BID
Candidiasis - indications for prophylaxis and first line tx
Recurrent infectionsFluconazole 150 mg PO daily
What is the most common serious opportunistic disease in women w/ HIV?