Wesley Campbell, MD, of U.S. Navy Medicine, presents "An AIDS-Defining Illness Presenting during Acute Retroviral Syndrome: A Case Discussion and Review of the Literature" for AIDS Clinical Rounds at UC San Diego
The UC San Diego AntiViral Research Center sponsors weekly presentations by infectious disease clinicians, physicians and researchers. The goal of these presentations is to provide the most current research, clinical practices and trends in HIV, HBV, HCV, TB and other infectious diseases of global significance. The slides from the AIDS Clinical Rounds presentation that you are about to view are intended for the educational purposes of our audience. They may not be used for other purposes without the presenter’s express permission. AIDS CLINICAL ROUNDS
Transcript
The UC San Diego AntiViral Research Center sponsors weekly presentations by infectious disease clinicians, physicians and researchers. The goal of these presentations is to provide the most current research, clinical practices and trends in HIV, HBV, HCV, TB and other infectious diseases of global significance. The slides from the AIDS Clinical Rounds presentation that you are about to view are intended for the educational purposes of our audience. They may not be used for other purposes without the presenter’s express permission.
AIDS CLINICAL ROUNDS
AN AIDS-DEFINING ILLNESS PRESENTING DURING ACUTE RETROVIRAL SYNDROME: A CASE DISCUSSION AND REVIEW OF THE LITERATURE FEBRUARY 21, 2014
LCDR Wesley Campbell, MC, USN, PGY-4
Disclosures
I have no relevant financial relationships with any commercial supporters.
Unlabeled/Investigational products and/or services will be mentioned in this CME offering.
Question
Of the following, what is the most frequently described opportunistic infection in adult patients with acute retroviral syndrome? A) Herpes zoster B) Pneumocystis pneumonia C) CMV colitis D) CMV pneumonitis E) Cryptococcal meningitis
Answer-B
Pneumocystis pneumonia Along with oral and esophageal candidiasis, the most
commonly described OI in ARS OIs are rare in ARS and felt to be a consequence of
transient CD4 T-cell depletion; nadir typically occurs 3-6 weeks post infection
Case
CC: New diagnosis of HIV
HPI: 21 y/o MSM college student diagnosed with acute retroviral syndrome 2 months prior in setting of prolonged gastrointestinal complaints
Pertinent History
Presented with gastrointestinal symptoms, associated lethargy, and decreased appetite in early October with brief observation on general surgery to rule out appendicitis. Diagnosed with viral enteritis.
After discharge from surgery service, spent time in Mexico with hospital admission there for ongoing symptoms. Received IV fluids, antibiotics and evaluation for hepatitis.
Evaluated on 1 November in ED due to 2 days of worsening GI symptoms. Initiated on ciprofloxacin/metronidazole for colitis.
Physical Exam
Initial Presentation: 8 Oct 2013 Afebrile; HR 62bpm; BP (111/68); RR 16/min; O2
96% RA Only diffuse abdominal discomfort on exam
Re-presentation: 1 Nov 2013 Afebrile; HR 104bpm; BP (106/65); RR 16/min; O2
97% RA Only diffuse tenderness documented
Labs
WBC Neut Bands Lymph
CBC 10/8/2013 3.8 48% NA 40%
CBC 11/1/2013 20.0 24% 37% 13%
Tbili AST ALT Alk Phos
LFTs 10/8/2013 0.6 52 59 67
LFTs 11/1/2013 1.1 93 85 85
Labs
Viral hepatitis panel Negative
C-diff PCR Negative
Stool Culture Negative
Fecal leukocytes Negative
Stool Crypto Ag Negative
Stool O&P Negative
HIV rapid Positive
Giardia Ag Negative
RPR Negative
Quantiferon Negative
Toxoplasmosis serology Negative
EBV serologies Negative
CMV PCR 16,169 copies
CMV titers Ig ordered, not collected
HIV Labs
Genotype B K103S mutation HIV ELISA pos; Indeterminate western blot (1Nov)
1 Nov 2013 3 Dec 2013 8 Jan 2014
CD4 count 524/6% 605/15% 390/13%
CD8 8054/0.07 2823/0.21 2214/0.18
VL 1,096,247 4,010,146 532,574
CT Image 8 Oct 2013
CT Image 1 Nov 2013
Hospital Course
Upper and lower endoscopy Upper Stomach- moderate gastropathy, mild patchy antral gastropathy Small hiatal hernia Mild duodenitis Normal esophagus
Lower Patchy colitis throughout colon with ulcer on ileocecal valve Patchy ileitis Rectal inflammation Small internal hemorrhoids
Endoscopy Images
Endoscopy Images
Endoscopy Images
Pathology
Duodenal mucosa with mild intraepithelial
lymphocytosis and focal villous blunting
Small and large bowel with scattered Cytomegalovirus (CMV) inclusions
Pathology- H&E
Pathology- Immunohistochemical
Discharged
Diagnosed with CMV colitis/enteritis and HIV infection
Started on IV ganciclovir, transitioned to oral, diarrhea resolved 3weeks thereafter
Enrolled in AVRC Acute HIV study
Clinical Questions
How often is acute seroconversion marked by an
opportunistic infection, namely CMV colitis?
What symptoms predominate in ARS that would have lead to earlier testing?
What options are there for first-line therapy in setting of baseline resistance mutation and high viral load?
Acute Retroviral Syndrome & OIs
Acute Retroviral Syndrome syndrome occurs in 10-90% of acute HIV infections (Sterling, PPID)
Opportunistic Infections in acute retroviral syndrome
(ARS) are even more rare Oral/esophageal candidiasis Pneumocystis pneumonia Cryptococcal meningitis
Other OIs in Acute Retroviral Syndrome
Remainder of literature is description of case reports M. Kansasii Cytomegalovirus pneumonia and hepatitis Cytomegalovirus colitis Cytomegalovirus encephalitis Focal segmental glomerulosclerosis- HIV nephropathy
CMV in HIV
Historically a disease of chronic infection with progression to Acquired Immunodeficiency Syndrome (AIDS)
Pre-ART: Occurred in 21-44% of patients with spectrum of targeted organ to disseminated disease (Masur 1996)
Today: Estimated at 0.75-3.2 cases per 100 person-
years (Salzberger 2005)
Detected in up to 30% of HIV patients with CD4<100
CMV Disease in ARS
2-3 published case reports of CMV gastrointestinal disease during ARS (none with indeterminate WB)
Data across cases changes with era of AIDS epidemic
CD4 count role not completely documented or explained in ARS, but likely represents decreased functional count Our patient had a CD4 count of 6% total lymphocyte count
HIV viral load over 100,000 copies may have some correlation to CMV infection Our patient had over 1 million copies
Question
What constellation of symptoms would represent the highest pretest probability for primary HIV infection? A) 19 y/o MSM who is in a monogamous relationship with
an HIV (+) partner with 5 days of headache, subjective fever, night sweats
B) 22 y/o heterosexual male with 1 week of malaise, subjective fevers and vomiting who had an unprotected sexual encounter 2 weeks prior
C) 20 y/o heterosexual male with multiple unprotected sexual encounters 2 months prior, with intermittent fever, rash, loss of appetite, myalgias, and loss of energy
*based on 2002 prospective cohort at UCSF
Answer-C
Prospective cohort from UCSF explored systemic complaints in patients being tested for HIV with risk factors for HIV exposure in preceding 3 months
Fever was only symptom highly sensitive for HIV infection, while combinations of symptoms increased specificity and likelihood ratio for primary infection Fever with rash 91% specific in adult patients Diarrhea was of low sensitivity 46%
Recognition of Seroconversion
Early identification Allows for appropriate screening Interventions during highly transmissible period
“Mononucleosis-Like” syndrome Nonspecific complaints often overlooked Requires exploration of possible risk factors What constellation of symptoms would trigger
evaluation?
Prospective Cohort- ARS Symptoms
Hecht 2002 (UCSF)
Prospective Cohort- ARS Symptoms
Hecht 2002
Prospective Cohort- Viral Load and Symptoms
Kelley 2007
Question
According to recent CDC assessments, the estimated rate of primary drug resistance in treatment-naïve patients is: A) 14.6% B) 25% C) 8.3% D) 12.1%
Answer- A
A-14.6%: CDC data from 2006 from 10 states and 1 public health department published in 2010 (Wheeler, et al. 2010)
B- 25%: Estimates for San Diego County with small cohort (Smith, et al. 2007)
C- 8.3%: 2004 estimates (Weinstock, et al. 2004)
D- 12.1%: East Coast cohort, industry sponsored through Merk (Huang, et al. 2008)
Transmitted Resistance- Testing
Primary resistance in U.S. estimated at 8.3% (2004)
Sax 2004
Sax, 2004
Resistance Testing In Unknown Duration of Infection
Smith, 2007
Transmitted Resistance- Recent Estimates
Huang, 2007
Transmitted Resistance- Recent Estimates
ARV resistance- 12.1% NNRTI- 9.8% NRTI- 4.5% PI- 1.8%
Predictors MSM CD<500
Huang, 2007
Specific NNRTI Mutation Prevalence
Wheeler 2006
A Regimen for Our Patient
Expressed interest in a single-pill regimen or once-daily regimen Ease of attending classes Social constraints
1 Nov 2013 3 Dec 2013 8 Jan 2014
CD4 count 524/6% 605/15% 390/13%
CD8 8054/0.07 2823/0.21 2214/0.18
VL 1,096,247 4,010,146 532,574
Question
True or false: Elvitegravir/cobicistat/tenofovir/emtricitabine (“Quad pill”) has been FDA approved for use in treatment-naïve patients with primary resistance to NRTIs and NNRTIs. A) True B) False
Answer- False
Original trials excluded patients with NRTI or NNRTI or PI mutations
K White*, et al. Emergent Drug Resistance from the HIV-1 Phase 3 Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Studies through Week 96 Presented at CROI 2013
K White*, et al. Emergent Drug Resistance from the HIV-1 Phase 3 Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Studies through Week 96 Presented at CROI 2013
Our Patient
Experienced an AIDS-defining illness at diagnosis
Exceedingly rare event with unknown implications on progression of disease or response to therapy
CMV enteritis resolution after short course of valganciclovir and rebound of his CD4 count implies limited disease
Clinical Plan
Patient has exhibited insight into complexities of his diagnosis
Discuss with patient protease inhibitor vs. integrase inhibitor-based regimen given available data Choices of ART influenced by early genotype testing and
viral load If placed on the “Quad pill” most likely resistance mutation
to emerge is M184V and becomes apparent by approximately12 weeks*
At last visit, treatment regimen was yet to be determined
*K White*, et al. Emergent Drug Resistance from the HIV-1 Phase 3 Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Studies through Week 96 Presented at CROI 2013
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