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MI3.10-13 | Blood & Tissue Parasites and HIV/AIDS — PBL Case

CLINICAL SETTING

Dr Sujata Rao runs a primary health centre (PHC) in a town in Maharashtra near a national highway. One afternoon, Ramesh, a 34-year-old truck driver, arrives with his wife and 8-year-old son. Ramesh has not had a proper check-up in years. His wife reports that for the past 8 months he has been losing weight, sweating profusely at night, and feeling increasingly tired. Recently he has had a cough that 'just won't go away'. He has a history of unprotected sexual contacts during long-distance routes. The son is also visibly underweight and listless. Dr Rao begins to piece together a picture that is larger than a single patient.

Trigger 1: Initial Presentation

Ramesh, 34 years, truck driver. Occupation: long-haul routes, Pune–Nagpur–Hyderabad. Presenting complaints: weight loss (~12 kg in 8 months), drenching night sweats, persistent dry cough for 3 months, generalised fatigue. No jaundice or rash reported. History: occasional injected drug use 4 years ago during a 'difficult period'; multiple unprotected sexual contacts with female sex workers; no condom use. Married, wife 28 years, son 8 years. Examination: weight 51 kg (BMI 17.6), generalised lymphadenopathy (cervical, axillary, inguinal) — firm, non-tender, nodes 1–2 cm; oral examination reveals white creamy patches on the tongue and buccal mucosa that bleed on scraping; mild hepatosplenomegaly. Temperature 38.2°C, pulse 98/min, SpO2 93% on room air.

DISCUSSION POINTS

What is your differential diagnosis for this combination of weight loss, night sweats, lymphadenopathy, and oral lesions in a patient with this social history? List at least three conditions in order of priority.
The oral white patches bleed on scraping. Name the organism most likely responsible and explain why this patient is susceptible to this infection at this stage.
What risk factors for HIV infection does Ramesh have? Classify them by transmission route (sexual, parenteral, vertical). Which family members are at risk and why?

Click to reveal Trigger 2: Investigations and HIV Diagnosis (discuss previous trigger first!)

Trigger 2: Investigations and HIV Diagnosis

Dr Rao refers Ramesh to the district hospital's ICTC (Integrated Counselling and Testing Centre). Pre-test counselling is performed. Results: 4th-generation ELISA (antigen-antibody combo): REACTIVE. Western blot: POSITIVE (bands for gp160, gp120, p24, gp41, p31). HIV-1 confirmed. CD4+ count: 94 cells/μL (normal 500–1,500). Viral load: 420,000 copies/mL. Chest X-ray: bilateral interstitial infiltrates, 'ground-glass' pattern, no consolidation, no hilar lymphadenopathy. Sputum AFB smear: negative (×2). LDH: 480 U/L (elevated). Sputum for Pneumocystis jirovecii (Grocott/GMS stain): round cysts with intracystic bodies detected. Wife tested: HIV-1 POSITIVE, CD4+ 310 cells/μL. Son tested: HIV-1 POSITIVE, CD4+ 280 cells/μL (diagnosis via PCR — child <18 months, so antibody test is inadequate).

DISCUSSION POINTS

Interpret Ramesh's test results: what does the CD4+ count of 94 cells/μL tell you about his immune status and what specific opportunistic infections are you now worried about at this threshold? Use the CD4+ count — OI correlation table.
The chest findings and LDH point to a specific pneumonia. Identify it, name the organism's taxonomic re-classification (previously considered a protozoan, now reclassified), and explain why co-trimoxazole is the drug of choice.
For HIV diagnosis in the 8-year-old son, why was PCR preferred over ELISA? What does a positive HIV antibody test mean in a child under 18 months born to an HIV-positive mother, and why is it insufficient for diagnosis?

Click to reveal Trigger 3: Management, ART, and Family Response (discuss previous trigger first!)

Trigger 3: Management, ART, and Family Response

Ramesh is started on ART: Tenofovir (TDF) + Lamivudine (3TC) + Dolutegravir (DTG) — 'TLD' regimen — along with co-trimoxazole for PCP. His wife is also initiated on ART. The paediatrician initiates age-appropriate ART for the son. Two weeks after starting ART, Ramesh develops new fever, worsening cough, and right cervical lymph node enlargement with tenderness — despite being adherent to ART. Repeat CD4+ is 160 cells/μL (rising from 94). His sputum is now AFB-positive (2+ on Ziehl-Neelsen stain). The clinical team diagnoses IRIS (Immune Reconstitution Inflammatory Syndrome) with unmasking TB.

DISCUSSION POINTS

Explain the mechanism of IRIS in Ramesh's case. Why does starting ART sometimes paradoxically worsen the clinical condition in patients with active or subclinical OIs? What are the principles of management of IRIS — should ART be stopped?
Discuss the antiretroviral regimen TLD (Tenofovir + Lamivudine + Dolutegravir): what class does each drug belong to, what viral enzyme/step does each target, and why is Dolutegravir preferred over older agents like Efavirenz in India's national programme?
Ramesh's son was infected perinatally. Describe the three windows for mother-to-child transmission of HIV (antepartum, intrapartum, postpartum). What interventions under India's PPTCT (Prevention of Parent-to-Child Transmission) programme could have prevented infection in the son?

Group Task Assignments

Group 1: HIV Immunopathogenesis and Opportunistic Infection Staging

Draw a timeline of Ramesh's HIV natural history from estimated infection to the current clinical state, mapping CD4+ count decline to opportunistic infections at each threshold (>500, 200–500, 100–200, <100 cells/μL).
Prepare a one-page summary of the CD4+ count — OI correlation table for the group, including: PCP (<200), Toxoplasma encephalitis (<100), CMV retinitis (<50), Cryptococcal meningitis (<100), MAC (<50).

Competencies: MI3.13

Group 2: Laboratory Diagnosis of HIV — Methods, Window Periods, Confirmatory Tests

Compare 1st through 4th generation HIV ELISA assays: what each detects, window period, and when each was used/is currently used. Use a table format.
Explain the HIV Western blot: which viral proteins are detected, what constitutes a positive result (WHO criteria), and why Western blot is used as a confirmatory test rather than a primary screening test.

Competencies: MI3.13

Group 3: PPTCT Programme and Vertical Transmission Prevention

Map the three routes of vertical HIV transmission and the approximate contribution of each to overall MTCT risk (without intervention vs with PPTCT).
Outline the key interventions of India's PPTCT programme: maternal ART, safe delivery practices, infant prophylaxis (NVP), and infant feeding guidance — including the rationale for each.

Competencies: MI3.13

Group 4: ART Pharmacology — Classes, Mechanisms, Resistance

Create a reference card for the 6 classes of antiretroviral drugs: NRTIs, NNRTIs, PIs, INSTIs, fusion inhibitors, CCR5 antagonists. For each: mechanism of action, example drug, and one key resistance mechanism.
Explain why HIV rapidly develops drug resistance (reverse transcriptase error rate + high viral turnover) and how HAART (triple therapy) overcomes this by requiring simultaneous mutations at multiple genomic sites.

Competencies: MI3.13

Learning Issues

Research these questions and bring your findings to the discussion.

[MI3.13] What are the immunological stages of HIV infection, and how does CD4+ count predict the risk of specific opportunistic infections?
[MI3.13] How does 4th-generation ELISA differ from earlier generations, and what is the standard confirmatory algorithm for HIV diagnosis in India?
[MI3.13] What is Immune Reconstitution Inflammatory Syndrome (IRIS)? What is its mechanism and how is it managed when TB is the unmasked co-infection?
[MI3.13] What are the classes and mechanisms of action of antiretroviral drugs, and why is triple therapy (HAART) necessary to prevent drug resistance?
[MI3.13] What are the three routes of perinatal HIV transmission and what PPTCT interventions can prevent them?
[MI3.11] Why is Pneumocystis jirovecii now classified as a fungus rather than a protozoan, and how does this affect treatment strategy?