HIV-Associated Wasting and Gastrointestinal Opportunistic Infections

1. HIV-associated Wasting
and Gastrointestinal
Opportunistic Infections
Prepared by: Dr. Keibren Robinson
PG-Y1, DM Internal Medicine
Moderator: Dr. K. Pate-Robinson, Infectious Disease Specialist

2. Outline
• Index Case
• History and Examination
• Investigations
• Assessment and Recommendations
• HIV-associated Wasting and GI opportunistic infections
• Epidemiology
• Aetiology/Pathophysiology
• Clinical Presentation
• Evaluation & Diagnostic Criteria
• Non-pharmacologic and pharmacologic interventions
• References
2

3. Index Case
• C. L.  28-year-old female.
• PC:
• Passing watery stool x 6/12
• Cough x 2/12
• White substance in mouth x 3/52
• HPC:
Nil known chronic illness. Of note, patient was diagnosed with C13 two-weeks
prior to presentation via rapid C13 test done at St. Joseph’s Hospital.
3

4. Index Case
Subsequently, she was commenced on TLD 1tab p.o. O.D. by doctor at St.
Joseph’s Hospital; and, later given a referral letter to UHWI for assistance with
care.
She was in her usual state of health up until 6-months prior to presentation
when she began to experience intermittent episodes of non-bloody, watery
diarrhea; ~3-4x/day, ¼ to ½ cup in volume, green-to-brown in color, and
occurring ~4-5x/week.
Associated with: fecal incontinence, tenesmus, loss of appetite, decreased oral
intake and quantified weight loss.
4

5. Index Case
She reports that prior to these symptoms she weighed 120lbs (=54kg) but notes
significant weight loss of ~20-25lbs (=9-11kg) over the 6-month period.
Additionally, she reports generalized weakness, loss of endurance and easy-
fatiguability.
2-months prior to presentation, she began to experience a wet, productive
cough of clear-to-yellow sputum associated with intermittent fever (subjectively
assessed and mostly occurring during the night), chills and night sweats.
5

6. Index Case
3-weeks prior to presentation, she notes white substances appearing in her
mouth (inner cheeks and back of throat) as well as on her tongue associated
with difficulty and occasional pain on swallowing, which further affected her
oral intake. She was commenced on Itraconzaole 200mg p.o. O.D. for same by
St. Joseph’s Hospital doctor – reports minimal-to-no relief.
In light of these symptoms as well as her being newly-diagnosed with C13, she
was referred to the ID service for assistance with management.
6

7. Index Case
• PMH:
• Nil of note.
• PSH:
• Nil of note.
• Dental Hx:
• She has not seen a dentist in >5-years.
• Lower left molar extraction x ~6-7years
prior.
• Nil h/o root canal.
• POH/PGH:
• Menarche:12-years old.
• Coitarche: 17-years old.
• LMP: 28/01/2023; regular.
• Nil h/o pregnancy or abortions.
• Nil pap smear.
• DH:
• TLD 1tab p.o. O.D., Itraconazole 200mg
p.o. O.D., Multivitamin.
• NKDA. Nil food allergies.
7

8. Index Case
• FH: Non-contributory.
• SH: Lives with her brother is 2-bedroom apartment. Good family support.
Works as a security guard. She does not smoke or drink alcohol.
• Sexual Hx:
• 5 sexual partners in total; all males.
• Monogamous. Genital sex only.
• Inconsistent barrier method use.
• Last sexual encounter – December 2022.
8

9. Review of Systems
• General: Night sweats✓, Lethargy✓, fever✓, weight loss✓, loss of appetite✓
• CVS: Chest pain°, Palpitations°, Orthopnea°, PND°, Leg swelling°
• RS: SOB°, cough✓, wheeze°, nasal congestion°, hemoptysis°
• GI: Oral lesions✓, nausea✓, vomiting✓, dysphagia✓, odynophagia✓, diarrhea✓
• GU: Vaginal discharge°, vaginal ulcers/sores°, warts°, urinary tract symptoms°
• CNS: Depression°, anxiety°, headaches°, neck pain/stiffness°, visual disturbance°,
seizures°, confusion°, altered mental status°, lightheadedness✓
• Skin: Rash✓, Itching✓, Ulcers°
9

10. A&E UHWI Course:
• V/S on presentation: BP 90/62mmHg, PR 108bpm, T 38.4°C,
RR 20 breaths/min, SpO2 96% on R.A.
• O/E: Young female with generalized wasting. MM pale pink + dry.
Oral thrush.
• IV access, 500cc IV fluid bolus then 100cc/hr, blood investigations, rapid
COVID-19 antigen test, rapid C13 test, Chest X-Ray, ECG, ABG.
• Referred to Internal Medicine on-call team.
10

11. Clinical Examination 11

12. Clinical Examination
Findings by I.D. Team:
• O/E: Young, ill-looking, cachectic female seen in nil distress. MM pale pink +
dry. AI, AC, warm to touch. Hydration status: skin dry, salivary pool
decreased. Oropharyngeal thrush✓. Lymphadenopathy✓ - right
supraclavicular and bilateral inguinal. Weight 77lbs (=35kg).
V/S: BP 120/71, PR 133, T 38.9°C (Tmax 39.5°C), RR 20, SpO2 98% on R.A.
• CVS: PR 133bpm – Regular. Pulse volume ⬆. Synchronous✓. Collapsing✓.
JVP⬌. Apex beat Lt. 5th ICS lateral to MCL. Thrills°, heaves°, Palpable
P2°. S1✓, S2✓, S3°, S4°. Murmurs°. Oedema°.
12

13. • RS: RR 20breaths/min. Trachea central. CEEB. TVF + VR normal.
PN – resonant. BS=Vesicular; slightly ⬇ to LZ bilaterally. Crepitations°,
Wheeze°, Rhonchi°.
• Abdomen: Scaphoid. Soft, depressible and mildly tender to epigastrium.
Guarding°, Rebound°, Renal angle°. Masses°. Organomegaly°.
Liver span=14cm. Bowel sounds normal. DRE – refused.
• NS: Alert. Oriented x3. HMF – intact. Nil focal deficits. ⬇ Bulk + normal
tone. Power 5/5 throughout. Reflexes 2+. Kernig°. Brudzinski°.
Clinical Examination
Findings by I.D. Team: 13

14. Clinical Examination
Findings by I.D. Team:
• Skin: Multiple, well-circumscribed hyperpigmented papules and nodules to
torso, mid-to-lower back and both UL + LL. Non-scarring alopecia.
Body Mass Index (BMI): 13.2 kg/m2 (Underweight) Mid-Upper Arm Circumference (MUAC): 9cm
14

15. INVESTIGATIONS 15

16. Complete Blood Count
CBC Result Reference Range
HGB 7.2 ⬇ 11.5-16.5 g/dL
HCT 24.1 ⬇ 37.0-47.0 %
MCV 70.1 ⬇ 81.1-96.0 fL
MCH 21.1 ⬇ 27.0-31.2 pg
Platelet Count 578 ⬆ 150-450 x109/L
WBC instrument 8.17 3.75-11.00 x10e9/L
Neutrophils (%) 70.45 40.00-75.00
Lymphocytes (%) 19.07 ⬇ 20.00-40.00
Monocytes (%) 8.75 2.00-10.00
Eosinophils (%) 0.37 ⬇ 1.00-6.00
Basophils (%) 1.36 ⬆ 0.00-1.00
16

17. Urea & Electrolytes
U&E Result Reference Range
Sodium 125 ⬇ 135-145 mmol/L
Potassium 3.2 ⬇ 3.5-5.0 mmol/L
Chloride 87 ⬇ 95-105 mmol/L
Bicarbonate 22 20-28 mmol/L
Urea 1.6 ⬇ 2.5-6.7 mmol/L
Creatinine 36 9-124 µmol/L
Magnesium 0.73 0.64-1.06 mmol/L
Calcium Total 2.18 ⬇ 2.25-2.75 mmol/L
Phosphorous 1.0 0.8-1.4 mmol/L
17

18. Liver Function Test
Proteins Result Reference Range
Total Proteins 83 64-84 g/L
Albumin 33 ⬇ 38-52 g/L
Globulin 50 ⬆ 18-38 g/L
Liver Function Result Reference Range
Bilirubin Direct 6 2-6 µmol/L
Bilirubin Total 11 4-18 µmol/L
Alkaline Phosphatase 68 15-105 U/L
Gamma-Glutamyl Transferase 31 10-70 U/L
Aspartate Transferase 28 7-32 U/L
Alanine Transferase 7 4-17 U/L
18

19. Other Lab Investigations
Glucose Result Reference Range
Glucose Random 6.4 2.5-9.0 mmol/L
Cardiac Result Reference Range
Lactate Dehydrogenase 495 ⬆ 105-200 U/L
• Rapid COVID-19 Antigen Test: NEGATIVE
• Rapid C13 Test: POSITIVE
19

20. Arterial Blood Gas
A-a O2 gradient: 20 mmHg
Expected A-a Gradient for Age: 11 mmHg
ABG on room air; RR 22breaths/min
• pH 7.560
• pCO2 28.7 mmHg
• pO2 94 mmHg
• HCO3 25.7 mmol/L
• BEecf 3 mmol/L
• sO2 98%
• Lac 2.16 mmol/L
20

21. ECG 21

22. Chest X-Ray 22

23. CD4 Count
CD4: 77 cells/µL
%CD4: 8.48%
23

24. Clinical Assessment 24

25. Assessment:
1. Newly-diagnosed C13 with evidence of advanced disease
• with AIDS-defining illness
• HIV-associated Wasting
• Oropharyngeal-esophageal candidiasis
• Likely PJP
2. Microcytic Hypochromic Symptomatic Anaemia
• Haemodynamically unstable
• Hb 7.2 g/dL
25

26. HIV-Associated Wasting (HIVAW)
&
GI Opportunistic Infections (GI OIs)
26
World Health Organization (WHO), 1998

27. HIV-associated Wasting (HIVAW)
In 1987, the US Centers for Disease Control and Prevention (CDC)
classified HIVAW as an AIDS-defining condition, defined by:
• Involuntary, progressive weight loss of >10% baseline body weight
accompanied by;
• Chronic diarrhea,
• Nutritional deficiencies,
• Fever, and
• Weakness
for 30-days in the absence of other related illnesses.
27
Centers for Disease Control and Prevention. HIV in the United States: the
stages of care. U.S. Department of Health & Human Services. 2020.

28. HIVAW – Epidemiology
The exact prevalence of HIVAW and the change over time have been
difficult to evaluate.
In a study by Tang et al., it was observed that (USA):
• For every 1% loss in weight, there was an 11% increase in the risk
of death.
• When weight loss was at least 10% from baseline weight, the
relative risk of mortality was increased nearly six-fold.
28
Tang et al. (2002). “Weight loss and survival in HIV-positive patients…”

29. HIVAW - Epidemiology
In 2009, Siddiqui et al. conducted a database analysis, USA:
• Among 12,187 continuously enrolled patients with HIV between
January 2005 and July 2007:
• 1,006 (8.3%) had evidence of HIVAW.
• Patients with evidence of HIVAW were older (44.1 vs. 42.6 years)
• More commonly male than female (8.8% vs. 5.3%).
• Median survival was markedly lower among HIV-infected men with
wasting (9.1 years; 95% confidence interval [CI] 8.4 – 9.6 years)
compared with HIV-infected men with no history of wasting
(11.6years; 95% CI 11.0–12.4years)
29
Siddiqui et. al., (2009). “Prevalence and cost of HIV-associated weight loss…”

30. HIVAW - Epidemiology
• In a 2022 study by Siddiqui et al., a total of 42,587 people living with
HIV/AIDS (PLWHA) were identified over the 2012–2018 study period.
• From the PLWHA study population 7804 met the definition of HIVAW.
• Estimated HIVAW cumulative prevalence between July 2012 and March
2019 was 18.3% (95% CI 18.0– 18.7%).
• Estimated annual prevalence was 2.7% per year (18.3/6.75-year study
period).
30
Siddiqui et. al., (2022). “HIV-associated wasting prevalence in the era of…”

31. HIVAW & GI OIs - Epidemiology
• The study population was predominantly male (61.7% in the HIVAW cohort
and 65.3% in the non-HIVAW cohort.
• The HIVAW cohort were more likely to be older with a mean age of 46.4
(12.0 SD) years vs. 43.5 (12.5 SD) years for the non-HIVAW cohort.
• The most common opportunistic infections in the HIVAW cohort were
severe candidiasis (13.1%), herpes zoster (10.7%), severe herpes simplex
(6.8%), and Pneumocystis jirovecii pneumonia (5.5%).
31
Siddiqui et. al., (2022). “HIV-associated wasting prevalence in the era of…”

32. 32
HIVAW - Epidemiology
Siddiqui et. al., (2022). “HIV-associated wasting prevalence in the era of…”

33. 33
Siddiqui et. al., (2022). “HIV-associated wasting prevalence in the era of…”

34. GI OIs: Oral Lesions 34
• Oral candidiasis (thrush)
presents with oral pain, ageusia
and dysphagia.
• Lesions usually present when CD4
count <200.
• The creamy white lesions are
located on the tongue surface
and on the buccal mucosa.
• Painful oral lesions are caused by
Herpes simplex virus (HSV).
• Vesicles breakdown to form
ulcers and have a tendency to be
severe and remain for a longer
duration in patients with
advanced HIV as compared with
the normal population.
Tx: Fluconazole,
Nystatin
Tx: Acyclovir,
famiciclovir,
Valacyclovir

35. GI OIs: Esophageal Lesions
• Esophagitis is common in advanced disease; at least one-third of
patients will suffer from esophageal disease.
• Candidal esophagitis  most frequent!
• CMV  most common viral pathogen of esophagitis!
• identified in 10-40% of endoscopic biopsies of esophageal lesions.
• Other causes (less common): EBV, HSV and HHV-6.
• Rare causes of esophagitis:
• Protozoal: Cryptosporidium parvum, Leishmania spp
• Fungal: Pneumocystis jirovecii
35

36. • A wide variety of protozoal, viral and bacterial pathogens are
responsible for diarrhea in AIDS patients.
• Cytomegalovirus  most common OI of the bowel!
• Other causes:
• Mycobacterium avium intercellulare (MAI)
• Cryptosporidium, Isospora, Cyclospora
• Non-typhoid Salmonella, Shigella, Campylobacter
• Sequel to the availability of HAART and antimicrobial prophylaxis
 Clostridium difficile
36
GI OIs: Small and Large Bowel Lesions

37. GI OIs: Small and Large Bowel Lesions
37

38. HIVAW – Aetiology/Pathophysiology
Multifactorial.
• Decreased energy intake (i.e. loss of appetite, malabsorption)
• Opportunistic infections
• Endocrine (hormonal) dysfunction
• Cytokines
38

39. HIVAW & GI OIs – Clinical Presentation
1. Decreased total body weight
2. Diarrhea
3. +/- Fever
• Unlike simple starvation, this weight loss
is primarily related to a loss of lean
muscle and is likely associated with
increased protein-turnover and other
hypermetabolic characteristics.
39
Figures 1 & 2: HIV Wasting Syndrome in a
Nigerian female failing Antiretroviral Therapy

40. HIVAW & GI OIs – Evaluation of Wasting 40
Medical History
• Anthropometric measurements: Height,
Weight, Ideal Body Weight (IBW), Body
Mass Index (BMI)
Labs
• CD4, VL, Total Protein, Albumin, CBC,
U&E, LFT, TSH, Stool Cx, OCP, C. diff
• Viral studies (CMV, Toxo, Hep B+C)
• Testosterone level (free and total for
male patients)
Psychological Assessment
• Depression, Eating disorder
Nutritional Assessment
• Nutritional requirements vs.
present intake
Functional Capacity Assessment
• Physical impediments, impact on
activities of daily living

41. HIVAW – Diagnostic Criteria
Patients must meet one (1) of the following:
Weight loss of greater than:
• 10% within 12-months or from baseline visit
• 7.5% within 6-months
• 5% within 3-months
At least 5% total BCM loss within 6-months
BMI <20 kg/m2
In men: BCM <35% of total body weight and BMI <27 kg/m2
In women: BCM <23% of total body weight and BMI < 27 kg/m2
BCM: body cell mass; BMI: body mass index
Reference: Clinical Infectious Diseases, Volume 73, Issue 11, 1 December 2021
41

42. HIVAW - Interventions 42
Non-Pharmacological
Interventions
Pharmacological
Interventions
Management of concurrent
disease states
Nutritional Assessment and
Counselling
Psychosocial/Situational
Intervention
Exercise
Antiretroviral therapy
Appetite stimulant
Protein anabolic agents
Anabolic/Androgenic steroids

43. Non-Pharmacologic Intervention for HIVAW 43
Management of concurrent disease states
• Opportunistic infections that interfere with swallowing (e.g.
candidiasis, oral herpes, CMV esophagitis)
• Aphthous ulcers
• Malignancy
• Depression
Nutritional Assessment and Counselling
• Dietitian/Clinical Nutritionist referral
• Maintenance of adequate food intake, high protein diet

44. 44
Psychosocial/Situational Assessment
• Depression may be an underlying cause of anorexia
• Charitable organizations (e.g. Food for the Poor Jamaica)
• Smoking cessation
• Addiction specialist referral
Exercise
• Maintain or increase activity levels and engage in mild-to-
moderate resistance exercise training when possible
Non-Pharmacologic Intervention for HIVAW

45. Pharmacologic Intervention for HIVAW
Intervention Pros Cons
Antiretroviral Therapy (ART) Primary therapy for HIVAW 
Treat underlying HIV
infection with ART.
Does not lead to weight gain,
but can help to minimize the
impact of disease factors
that contribute to wasting.
45

46. Pharmacologic Intervention for HIVAW
Appetite Stimulants Pros Cons
Megestrol acetate
(Megace®)
Potent. FDA-approved for HIV-
related cachexia. Comes as
suspension (no added pill
burden).
Cost $$. Majority of weight gain is fat.
Side effects: sexual dysfunction,
hypogonadism, adrenal suppression,
DVT, AVN
Cyproheptadine
(Periactin®) Stimulates appetite. Cheaper
than Megace®.
Off-label use as appetite stimulant.
FDA-approved antihistamine. Specific
protein catabolic effects.
Dronabinol (Marinol®) FDA-approved as an AIDS-
related appetite stimulant.
Improvement in self-reported
appetite. Improvements in
nausea and mood.
Weight does not increase consistently.
Side effects: euphoria, dizziness,
affects concentration.
46

47. FDA-Approved Appetite Stimulants for HIVAW
Drug
Name
Brand
Name
Formulations Dosing Instructions
Dronabinol Marinol® 2.5mg, 5mg, 10mg,
10mg oral capsule
Starting dose: 2.5mg B.D.
Titrate dose based on tolerance and
response up to a maximum dose of
10mg B.D.
Syndros® 5mg/mL oral
solution
Starting dose: 2.1mg B.D.
Titrate dose based on tolerance and
response up to a maximum dose of
8.4mg B.D.
Megestrol
acetate
Megace® 5mg/mL oral
solution
Starting dose: 2.1mg B.D.
Titrate dose based on tolerance and
response up to a maximum dose of
8.4mg B.D.
Megace-ES® 125mg/mL oral
suspension
625mg/day (5mL)
47

48. Pharmacologic Intervention for HIVAW
Intervention Pros Cons
Protein Anabolic Agents
Recombinant Human Growth
Hormone (Serostim®)
FDA-approved for HIV patients with
wasting or cachexia with concomitant
ART. Increases weight and decreases
fat.
Cost: $20K for 12-week course of
therapy. Subcutaneous injection.
Weight is not maintained following
drug discontinuation.
Side effects: myalgia, facial
puffiness, diarrhea
Anabolic/Androgenic Steroids
Testosterone,
Nandrolone,
Oxandrolone
Increase body mass and muscle mass in
men with wasting and low testosterone
levels. Transdermal testosterone (patch,
gel). Oral oxandrolone.
Decreases HDL (risk of CV disease).
IM injection for testosterone/
nandrolone.
Off-label use (not FDA-approved)
role for women unknown.
??Increased risk of prostate ca??
48

49. Recommendations by I.D.
for Index Case:
1. Bactrim 15-20mg/kg/day (in divided doses)
2. Fluconazaole 400mg p.o. STAT, then 200mg
p.o. OD x 2/52
3. Gravol 50mg I.V. TDS
4. IV Fluids 3L/24hrs
5. For CHARES psychosocial team assessment
6. Dietitian referral
7. GI prophylaxis
8. Stool C&S, OCP, C. difficile
9. Hep B+C, VDRL, C13, Toxo IgG/IgM,
CMV IgG/IgM
10. Chest physio
11. SpO2 monitoring
12. For 6-minute walk test
13. Anemia screen
14. Consider GI consult for UGIE
14. I/O with stool charting
15. Supportive care
16. Case to be discussed
49

50. Update on Index Case, C.L.:
• Improvement in her appetite and began to tolerate oral diet.
• Resolution of diarrhea.
• In-hospital dietitian consultation with meal plans.
• Also, received follow-up/review date.
• Given detailed referral note to CHARES for follow-up care.
• Discharged for home.
50

51. Summary
• HIV-associated wasting increases morbidity and mortality but has
received little attention, including prospective clinical research, in the
era of modern ART.
• The true impact of all of the discussed treatment options on survival is
questionable.
• The GI tract is a common site for clinical expression of HIV; and,
progressive immunosuppression is linked to an increase in the prevalence
of GI features.
51

52. Summary
• Virtually all GI opportunistic infections happen when the CD4+ T
cell count is less than 200 cells/µL and subsequently responds to
immune reconstitution facilitated by highly active antiretroviral
therapy (HAART).
• The data presented suggests the need to monitor for unintentional
weight loss in PLWHA, understand the complex and multifactorial
etiologies of HIVAW, and evaluate the risks of HIVAW with GI
opportunistic infections as well as other comorbidities.
52

53. References
• Badowski M, Pandit NS. Pharmacologic management of human immunodeficiency virus wasting syndrome. Journal of
Pharmacotherapy. 2014;34(8):868-881.
• Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case
definition for AIDS among adolescents and adults. MMWR Recomm Rep. 1992;41(RR-17):1-19.
https://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm (Accessed on February 18, 2023)
• Ogoina, D., Obiako, R., & Muktar, H.M. (2010). HIV Wasting Syndrome in a Nigerian Failing Antiretroviral Therapy: A Case Report
and Review of the Literature. Case Reports in Medicine, 2010.
• Polsky B, Kotler D, Steinhart C. HIV-associated wasting in the HAART era: guidelines for assessment, diagnosis, and treatment.
AIDS Patient Care STDS. 2001;15(8):411-423.
• Tang AM, Forrester J, Spiegelman D, Knox TA, Tchetgen E, Gorbach SL. Weight loss and survival in HIV-positive patients in the era
of highly active antiretroviral therapy. Journal of Acquired Immune Deficiency Syndrome 2002; 31:230–236.
• Siddiqui J, Phillips AL, Freedland ES, Sklar AR, Darkow T, Harley CR. Prevalence and cost of HIV-associated weight loss in a
managed care population. Current Medical Research and Opinion 2009; 25:1307– 1317.
• Siddiqui J, Samuel SK, Hayward B, Wirka KA, Deering KL, Harshaw Q, Phillips A, Harbour M. HIV-associated wasting prevalence in
the era of modern antiretroviral therapy. AIDS. 2022 Jan 1;36(1):127-135. doi: 10.1097/QAD.0000000000003096. PMID:
34628440; PMCID: PMC8654247. https://pubmed.ncbi.nlm.nih.gov/34628440/(Accessed on February 20, 2023)
• Smith PD, Eisner MS, Manischeniwitz JF, Gill VJ, Masur H, Fox CF. Esophageal disease in AIDS is associated with pathologic
processes rather than mucosal human immunodeficiency virus type I. J Infect Dis 1993;167:547-52.
53

54. Thank you for listening! 