Hivaids

Definition

• AIDS: HIV + CD4 count • 200/mmJ or opportunistic infection (Ol) or malignancy Epidemiology

1 million Americans infected w/ HIV; 6th leading cause of death in 25-44 y-old age group

• -40 million individuals infected worldwide

• Routes: sexual (risk is 0.3% for male-to-male, 0.2% for male-to-female. 0.1% for female-

to-male transmission), IVDA, transfusions, needle sticks (0.3%). vertical (15-40%) Acute retroviral syndrome (ARS)

• Occurs in 40-70% of HIV © Pts 4 wks after infection; © ELISA. © viral load

• Manifestations: mononudeosis-like syndrome (t incidence of mucocutaneous and neurologic manifestations c/w EBV or CMV)

Diagnostic studies

• ELISA for HIV-1 Ab: • 1-12 wks after acute infection; -99% Se; 1° screen test

• Western blot © if _-2 bands from diff regions of HIV genome; -99% Sp; confirmatory after © EUSA

• Rapid preliminary tests: 4 Ab tests; use saliva, plasma, blood, or serum; 99% Se & Sp

• PCR (viral load): detects HIV-1 RNA in plasma; standard (limit 200-400 copies per ml) and ultrasensitive assays (limit 20-75 copies per ml). 2-4% false © rate, but usually low # of copies; in contrast, should be very high (>750k) in primary infection.

• When testing, obtain informed consent for ELISA. Western, and PCR

• HIV screening is recommended for all Pts in all health care settings (MMWR Sept 22.2006)

• CD4 count: not a dx test per se, as may be HIV © and have a normal CD4 count or may have a low CD4 count and not be HIV ©; many other illnesses impact CD4 count Initial approach to HIV © Pt

• Document HIV infection (if adequate documentation is not available, repeat dx studies)

• H & P (evidence of Ols, malignancies. STDs); review all meds

• Laboratory evaluation: CD4 count, viral load, genotype test. CBC with diff.. Cr. lytes.

LFTs, fasting gle, PPD, syphilis, toxoplasmosis. CMV. fasting lipids, hepatitis serologies, baseline CXR, Pap smear in women

Antiretrovirals

Drugs

Side Effects

zidovudine (AZT; Retrovir)

class:

stavudine (d4T; Zerit)

Gl intol. common (less w/ 3TC, ABC,TDF)

didanosine (ddl; v«Jex)

facial/peripheral lipoatrophy (less w/ 3TC. FTC.

zalcitabine (ddC; H.v.d)

ABC.TDF)

£

abacavir (ABC; Zugen)

lactic acidosis (less w/ 3TC/FTC. ABC.TDF)

z

lamivudine (3TC; Ep«w)

ddl & d4T — peripheral neuropathy & pancreatitis

tenofovir (TDF: v.rend)

AZT — BM suppression

emtricitabine (FTC; Emtmi)

ABC — hypersensitivity (3%)

H

nevirapine (NVP; Viramune)

class: rash, induce or inhibit CYP«m

cc z

efavirenz (EFV; Swtiva)

EFV - CNS effects

Z

delaverdine (DLV; Rescnptor)

amprenavir (APV; Ajefieraie)

ctoss:

atazanavir (ATV; Rcyatai)

Gl intolerance

indinavir (IDV; Cttxivan)

inhibit CYP4W

fosamprenavir (FPV; Uxiva)

type II DM

_

lopinavir/riton. (LPV/r; Kaieva)

ritonavir (RTV; Norw)

truncal obesity

nelfinavir (NFV; Vincept)

hyperlipidemia (less w/ ATV)

saquinavir (SQV; Fortmic)

IDV nephrolithiasis

tipranavir (TPV; Apovus)

darunavir (DRV; Prtaisn)

ü

enfurvitide (T20; Fuzeon)

injection site reaction

NRTI = nucleoside/tide reverse transcriptase inhibitor; NNRTI = nonnudoosidc RTI; PI = protease inhibitor: Fl = fusion Inhibitor

NRTI = nucleoside/tide reverse transcriptase inhibitor; NNRTI = nonnudoosidc RTI; PI = protease inhibitor: Fl = fusion Inhibitor

• Use of antiretrovirals should be done in consultation with an HIV specialist as recommendations continue to be in flux and drug resistance and adverse reactions can be complicated to manage. Below are some guidelines for initiation (/A/vw 2006296:827).

Indications for initiation of therapy (HAART) AIDS or symptomatic HIV (eg. thrush, unexplained fevers) asymptomatic + high viral load (>35-50.000 copies/ml) or low CD4 (consider at 200-350/mm\ definite at 200/mm3) Resistance testing recommended for all Pts in US starting therapy Regimens {¡ama 2006.296 827)

[NNRTI - 2 NRTI] or [PI (• low-dose ritonavir) ♦ 2 NRTI]

NNRTI (EFV) - 2 NRTI better tolerated and achieved greater virologie suppression c/w PI (NFV) t 2 NRTI or 4-drug regimen (Loneet 2006:368287) EFV - TDF • FTC reasonable regimen (superior to EFV . AZT • 3TC; nejm 2006:354:251) ? NRTI • [NNRTI or PI] better tolerated and as effective as 3 drugs (tancer 2006:368.2125) Integrase inhibitors under study (lancet 2007:369:1261) Viral load should i 1 log copies/ml per month

Initiation of antiretrovirals may transiently worsen existing Ols for several wks b/c t immune response ("Immune Reconstitution Syndrome" or 1RS) If Rx needs to be interrupted, stop oil antiretrovirals to minimize development of resistance Failing regimen = unable to achieve undetectable viral load (> perhaps okay if < 10k: lone« 2004:364:51). * viral load. 1 CD4 count, or clinical deterioration (with detectable viral load consider genotypic or phenotypic assay)

Ol Prophylaxis

Ol

Indication

1° Prophylaxis

Tuberculosis

® PPD (£5 mm) or High-risk exposure

INH + vitamin B«, x 9 mo

Pneumocystis jirovcci

CD4 count 200/mm3 or CD4% <14% or thrush

TMP-SMX DS or SS qd or DS tiw or dapsone 100 mg qd or atovaquone 1500 mg qd or pentamidine 300 mg inh q4wk

Toxoplasmosis

CD4 count <100/mm3 and ® Toxoplasma serology

TMP-SMX DS qd or dapsone 200 mg qd ♦ pyrimethamine 75 mg qd » leucovorin 25 qwk

MAC

CD4 count ■ S0/mmJ

azithro 1200 mg qwk or clarithro 500 mg bid

Stop 1° prophylaxis if CD4 > initiation threshold >3-6 mo on HAART

Stop 2" prophylaxis (maintenance therapy of existing Ol; drugs and doses differ for different Ols) if there has been clinical resolution or stabilization and CD4 thresholds have been exceeded x 3-6 mo

(mmwr June 14.2002)

(mmwr June 14.2002)

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