Mountain West AIDS Education and Training Center

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1 Mountain West AIDS Education and Training Center Back to Basics: CMV Shireesha Dhanireddy, MD 21 July 2016 This presentation is intended for educational use only, and does not in any way constitute medical consultation or advice related to any specific patient.

2 Objectives/Overview Viral Basics Clinical Manifestations in patients with HIV Diagnosis Treatment Reactivation vs Infection

3 Viral Basics Member of herpes virus family (HHV-5) Double-stranded DNA virus Ubiquitous Primary infection often asymptomatic, mild flu-like symptoms, mono-like illness Leads to life-long persistence (viral latency) Disease in HIV+ patients is almost always from reactivation (or reinfection)

4 Viral Basics ~60% of US adult population infected - > 90% seroprevalence in MSM Transmitted from close person to person contact with someone shedding virus [through saliva, congenital, sexual, transfusion, SOT] Disease occurs in HIV+ patients with CD4 counts < 50 Incidence of CMV disease in HIV has decreased with ART

5 Retinitis Colitis Esophagitis Neurologic disease Clinical Manifestations of CMV in HIV+ Persons Pneumonitis rarely seen in HIV, even though seen in stem cell transplant patients

6 CMV Retinitis Most common CMV-associated disease in HIV+ persons Symptoms - Asymptomatic - Floaters - Scotomata (blind spots) - Visual field defects

7 CMV Retinitis

8 CMV Retinitis: Diagnosis Clinical diagnosis characteristic fundoscopic findings in patient with CD4 count < 50 Immediate ophthalmologic evaluation by someone experienced No laboratory or vitreal studies needed for diagnosis

9 Case 45 year old man presents with diarrhea, 20 lb weight loss, and abdominal pain. Diagnosed with HIV and CD4 count 5. AFB blood culture pending. CMV PCR from blood is 5000 copies/ml. CT abdomen shows mildly thickened sigmoid colon.

10 What would you do? A. Await AFB blood culture as this is likely MAC B. Start ART immediately as likely HIV wasting C. Start ganciclovir for CMV colitis D. Don t know. Need more information

11 Is CMV in blood diagnostic of disease? Viremia can be present in patients with low CD4 counts in the absence of disease Presence of CMV viremia has poor positive predictive value for diagnosis of disease Absence of viremia does NOT rule out disease

12 CMV Colitis Symptoms: weight loss, anorexia, abdominal pain, severe diarrhea, malaise Can cause perforation and present as acute abdomen Imaging may show colonic thickening

13 CMV Esophagitis Most common cause of esophagitis in HIV+ patients with CD4 < 50 is Candida CMV esophagitis presents with similar symptoms odynophagia, nausea, epigastric pain Patients who fail to respond to treatment for esophageal candidiasis should have EGD to rule out HSV and CMV

14 CMV GI Disease: Diagnosis Visualization of mucosal ulcerations on endoscopy Histopathology intranuclear and intracytoplasmic inclusions

15 CMV Neurologic Disease Can present as encephalitis, ventriculoencephalitis (V-E), polyradiculomyelopathy (Guillian-Barre-like syndrome) CMV V-E presents more acutely with focal deficits and generally has poor prognosis Typically diagnosed by clinical and radiographic findings in addition to CSF CMV PCR

16 Diagnosis Distinguish between replication (reactivation) vs disease Evidence of organ involvement CMV PCR from blood not diagnostic of disease and negative results do not rule out active disease CMV IgG not helpful as many patients (particularly MSM) have been exposed but negative result makes disease less likely

17 Should we screen patients at entry to care for CMV seropositivity? OI guidelines: - May test patients at low risk with CMV Ab (BIII level recommendation) - Low risk = Not MSM, No IDU, No exposure to children in day care centers - No testing necessary for all other patients

18 Treatment CMV Retinitis: - Oral valganciclovir V-GCV (or IV ganciclovir GCV) induction x 21 days then oral V-GCV x at least 3-6 months + lesions inactive + CD4 count > GCV ocular implant no longer made - Intravitreal GCV or foscarnet in addition to systemic therapy for sightthreatening lesions - Frequent ophtho exams

19 Treatment CMV GI disease: - GCV initially (may switch to V-GCV if able to take po) x 21 days (or symptoms resolve) - No maintenance (or secondary prophylaxis recommended) CMV CNS disease: - GCV + foscarnet - Duration?? based on clinical response Timing of ART: Within 2 weeks, except may consider delaying for CNS disease

20 CMV Prevention If seronegative for CMV, recommend condom use, handwashing, CMV neg blood if need transfusion No primary prophylaxis recommended

21 CMV: Key Points Seroprevalence high, especially in MSM, so serologic testing not useful Almost all disease is reactivation in HIV Most common clinical disease in HIV is retinitis Important to diagnose disease and distinguish from CMV replication without end organ disease

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