2.3 HIV/AIDS & Opportunistic Infections

HIV/AIDS & Opportunistic Infections

Kenya has made major strides in combatting the Human Immunodeficiency Virus (HIV) epidemic, pursuing the UNAIDS 95-95-95 targets (95% of people living with HIV knowing their status, 95% of diagnosed individuals on antiretroviral therapy, and 95% of those on ART achieving viral suppression). For the Clinical Officers Council licensure examination, candidates must know the national testing algorithm, the Universal "Test and Treat" mandate, first-line Dolutegravir-based regimens, viral load monitoring cascades, and the acute diagnosis and treatment of life-threatening opportunistic infections (OIs).

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1. HIV Diagnosis & Testing Strategy in Kenya

HIV diagnosis in Kenya utilizes a validated rapid serial testing algorithm on whole blood:

1. Screening Assay (Test 1): Highly sensitive rapid test (e.g., Determine HIV-1/2). If non-reactive, the patient is confirmed HIV-negative.
2. Confirmatory Assay (Test 2): Administered only if Test 1 is reactive, utilizing a highly specific rapid test (e.g., First Response). If reactive on both assays, the individual is confirmed HIV-positive.
3. Tie-Breaker Assay (Test 3): Employed if Test 1 and Test 2 yield discordant results. If Test 3 is reactive, the patient is declared positive; if non-reactive, the status is inconclusive, and the patient must return for repeat testing in 14 days.

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2. Antiretroviral Therapy (ART): Principles & Regimens

Universal "Test and Treat" Policy

Kenya mandates that combination antiretroviral therapy (cART) be initiated in all individuals confirmed to be living with HIV, regardless of CD4 cell count or WHO clinical stage. ART should be initiated rapidly, preferably on the same day as diagnosis (if the patient is clinically stable and mentally prepared) or within 14 days, provided active central nervous system opportunistic infections (such as Cryptococcal meningitis or TB meningitis) have been clinically excluded.

Preferred First-Line ART Regimens

PREFERRED FIRST-LINE ADULT & ADOLESCENT REGIMEN (Weight ≥ 30 kg):
  TLD (Fixed-Dose Combination Single Tablet Once Daily):
    • Tenofovir Disoproxil Fumarate (TDF) 300 mg
    • Lamivudine (3TC) 300 mg
    • Dolutegravir (DTG) 50 mg

• Dolutegravir (DTG): A second-generation Integrase Strand Transfer Inhibitor (INSTI). DTG blocks the catalytic activity of HIV integrase, preventing insertion of proviral DNA into the host genome. It offers rapid viral suppression (median time to <50 copies/mL is 4 weeks), an extremely high genetic barrier to resistance, once-daily dosing, and minimal metabolic side effects.
• Tenofovir Disoproxil Fumarate (TDF): A nucleotide reverse transcriptase inhibitor (NtRTI). Provides potent anti-HIV and anti-Hepatitis B virus (HBV) coverage. Major toxicities include proximal renal tubular dysfunction (Fanconi syndrome) and gradual bone mineral density loss.
• Lamivudine (3TC): A nucleoside reverse transcriptase inhibitor (NRTI). Well-tolerated with dual activity against HIV and HBV.

Special Clinical Situations & Alternative First-Line Regimens

1. Pre-existing Renal Impairment (Creatinine Clearance CrCl <50 mL/min):
   • TDF causes nephrotoxicity and is contraindicated.
   • Substitute TDF with Abacavir (ABC): Regimen is ABC (600 mg) + 3TC (300 mg) + DTG (50 mg).
   • Safety Note: Screen for the HLA-B*5701 allele where feasible; presence of this allele carries high risk of severe Abacavir hypersensitivity reaction (fever, rash, GI symptoms, dyspnea).
2. Concurrent Tuberculosis Treatment (Rifampicin Drug Interaction):
   • Rifampicin is a potent inducer of hepatic cytochrome P450 3A4 (CYP3A4) and UDP-glucuronosyltransferase 1A1 (UGT1A1), reducing plasma DTG concentrations by approximately 75%.
   • Clinical Action: Prescribe an additional single tablet of Dolutegravir 50 mg taken 12 hours after the once-daily TLD tablet (providing DTG 50 mg twice daily). Continue this supplemental DTG dose throughout TB treatment and for 2 weeks following rifampicin discontinuation.
3. Severe Neuropsychiatric Reactions to DTG or Documented Intolerance:
   • Alternative: TDF (300 mg) + 3TC (300 mg) + Efavirenz (EFV 400 mg) or a boosted protease inhibitor regimen.
4. Pediatric Formulations (<30 kg):
   • Use pediatric dispersible Dolutegravir 10 mg tablets combined with Abacavir/Lamivudine (ABC/3TC) dispersible tablets, approved for infants weighing down to 3 kg.

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3. Baseline Evaluation & Viral Load Monitoring Cascade

Essential Baseline Investigations Prior to / at ART Initiation

• Serum Creatinine and estimated GFR (assesses baseline renal safety for TDF).
• Complete Blood Count (rules out baseline severe cytopenias).
• Alanine Aminotransferase (ALT) and Hepatitis B Surface Antigen (HBsAg).
• Baseline CD4 cell count (defines immunological vulnerability and guides OI prophylaxis).
• Reflex Serum Cryptococcal Antigen (CrAg) screening for all patients with CD4 <200 cells/μL.
• Sputum GeneXpert TB screening if any symptom screen parameter is positive.
• Urine pregnancy test in women of reproductive age.

Viral Load Monitoring Schedule & Action Thresholds

Viral load testing is the gold standard for monitoring treatment response and detecting treatment failure.

• Testing Timeline:
  • First routine Viral Load: 6 months after initiating ART.
  • Second routine Viral Load: 12 months after initiating ART.
  • Subsequent routine Viral Loads: Annually (every 12 months) if the patient remains virally suppressed.
  • Pregnant and Breastfeeding Women: Tested more frequently: at baseline, 3 months, 6 months, and every 6 months thereafter until complete cessation of breastfeeding.

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4. Major Opportunistic Infections: Clinical Management

Opportunistic infections occur as immune defenses decline, particularly below specific CD4 cell thresholds.

CD4 CELL THRESHOLDS FOR MAJOR OPPORTUNISTIC INFECTIONS:
  • CD4 < 350 cells/μL: Pulmonary Tuberculosis, severe bacterial pneumonias, Herpes zoster
  • CD4 < 200 cells/μL: Pneumocystis jirovecii pneumonia (PCP), Cryptococcal meningitis
  • CD4 < 100 cells/μL: Cerebral Toxoplasmosis, Disseminated Cryptococcosis
  • CD4 < 50 cells/μL:  Cytomegalovirus (CMV) retinitis, Mycobacterium avium complex (MAC)

1. Cryptococcal Meningitis (CM)

• Etiology: Cryptococcus neoformans, an encapsulated budding yeast found in pigeon droppings and soil. Enters via respiratory tract and disseminates to the meninges.
• Clinical Presentation: Subacute onset of severe persistent headache, intermittent fever, neck stiffness, photophobia, confusion, and cranial nerve palsies (CN VI diplopia) due to elevated intracranial pressure. Classical meningeal signs may be absent in advanced immunosuppression.
• Diagnostic Protocol:
  • Reflex Serum CrAg Screening: Mandatory for all asymptomatic patients with CD4 <200 cells/μL. If positive, perform immediate lumbar puncture to rule out subclinical meningitis. If CSF is negative, provide pre-emptive oral Fluconazole (800 mg daily for 2 weeks, then 400 mg daily for 8 weeks, then 200 mg daily maintenance).
  • Lumbar Puncture (LP): Opening pressure typically elevated (>200 mm $\text{H}_2\text{O}$). CSF analysis reveals lymphocytic pleocytosis, elevated protein, low glucose, positive India Ink capsule stain (yeast cells surrounded by clear halos), and positive CSF CrAg Lateral Flow Assay (>98% sensitivity).
• Treatment Protocol (WHO / Kenya Guidelines):
  • Induction Phase (14 Days): Preferred regimen is Single high-dose Liposomal Amphotericin B (10 mg/kg IV on Day 1) combined with oral Flucytosine (100 mg/kg/day divided in 4 doses for 14 days) PLUS oral Fluconazole (1,200 mg daily for 14 days). Alternative: Amphotericin B deoxycholate (1 mg/kg/day IV) + Flucytosine for 7 days, followed by Fluconazole 1,200 mg daily for 7 days.
  • Consolidation Phase (8 Weeks): Oral Fluconazole 800 mg daily for 8 weeks.
  • Maintenance Phase (Secondary Prophylaxis): Oral Fluconazole 200 mg daily until the patient has achieved a CD4 count >200 cells/μL for at least 6 months on effective ART with suppressed viral load.
  • Management of Raised Intracranial Pressure: Perform daily therapeutic lumbar punctures removing 20 to 30 mL of CSF to keep opening pressure <200 mm $\text{H}_2\text{O}$.
  • CRITICAL TIMING RULE: DELAY ART initiation for 4 to 6 weeks after starting antifungal therapy. Early ART initiation triggers catastrophic central nervous system Immune Reconstitution Inflammatory Syndrome (CNS-IRIS), cerebral edema, tentorial herniation, and death.

2. Pneumocystis Jirovecii Pneumonia (PCP / PJP)

• Etiology: Pneumocystis jirovecii, an atypical opportunistic fungus. Predominates at CD4 <200 cells/μL.
• Clinical Presentation: Subacute, progressive exertional dyspnea, dry non-productive cough, chest tightness, low-grade fever, and tachypnea. A classic diagnostic hallmark is marked hypoxemia and exercise-induced oxygen desaturation out of proportion to minimal auscultatory chest findings.
• Chest Radiography: Symmetrical, diffuse, bilateral perihilar interstitial or alveolar ground-glass infiltrates ("bat-wing" or "butterfly" distribution).
• Treatment Regimen:
  • High-Dose Co-trimoxazole (TMP-SMX): Trimethoprim component 15 to 20 mg/kg/day (Sulfamethoxazole 75–100 mg/kg/day) administered orally or intravenously in 3 to 4 divided doses for 21 days (equivalent to two double-strength tablets [160/800 mg] three to four times daily).
  • Mandatory Adjunctive Corticosteroids: Indicated for moderate-to-severe PCP, defined by an arterial oxygen tension ($\text{PaO}_2$) <70 mmHg on room air, an alveolar-arterial oxygen gradient $\ge$35 mmHg, or room air $\text{SpO}_2 <92%$.
  • Prednisolone Dosing: 40 mg orally twice daily for Days 1 to 5, then 40 mg once daily for Days 6 to 10, then 20 mg once daily for Days 11 to 21. Corticosteroids must be initiated before or concurrently with antibiotic therapy to prevent the inflammatory surge caused by lysing fungal cells.
  • ART Timing: Unlike Cryptococcal meningitis, ART should be started early within 2 weeks of PCP diagnosis once acute respiratory failure stabilizes.

3. Cerebral Toxoplasmosis

• Etiology: Toxoplasma gondii, an obligate intracellular protozoan parasite transmitted via ingestion of undercooked meat containing tissue cysts or cat feces containing oocysts. Occurs at CD4 <100 cells/μL.
• Clinical Presentation: Subacute focal neurological deficits (hemiparesis, aphasia, cranial nerve palsies), focal or generalized seizures, dull progressive headache, fever, and altered mental status.
• Neuroimaging (Contrast CT / MRI): Multiple, bilateral, ring-enhancing lesions with surrounding vasogenic edema, with a predilection for the basal ganglia, thalamus, and hemispheric corticomedullary junctions.
• Treatment:
  • Preferred: Sulfadiazine (1,000–1,500 mg QID) + Pyrimethamine (200 mg loading dose, then 50–75 mg daily) + Folinic acid (Leucovorin 10–25 mg daily) to prevent pyrimethamine bone marrow suppression, for 6 weeks.
  • Resource-Limited Setting Alternative: High-dose Co-trimoxazole (TMP 10 mg/kg/day divided BD) for 6 weeks. Systemic dexamethasone is reserved for lesions causing severe mass effect and midline shift.

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5. Prophylaxis & PMTCT Protocols

Cotrimoxazole Preventive Therapy (CPT)

• Formulation: 1 Double-Strength tablet (960 mg: 160 mg Trimethoprim / 800 mg Sulfamethoxazole) orally once daily.
• Indications: All HIV-positive individuals with CD4 $\le$350 cells/μL, WHO Clinical Stage 3 or 4, all pregnant/breastfeeding women, and all HIV-positive patients living in malaria-endemic zones regardless of CD4 count.
• Protective Coverage: Prevents PCP, cerebral toxoplasmosis, malaria, isosporiasis, and severe bacterial respiratory/gastrointestinal infections.

Prevention of Mother-to-Child Transmission (PMTCT)

• Maternal Regimen: Immediate, lifelong TLD initiated upon diagnosis in all pregnant and breastfeeding women.
• Infant Prophylaxis:
  • Low Risk (Mother on ART >4 weeks prior to delivery with suppressed VL <1,000 copies/mL): Daily Zidovudine (AZT) or Nevirapine (NVP) for 6 weeks.
  • High Risk (Mother on ART <4 weeks, VL $\ge$1,000 copies/mL, or newly diagnosed during labor/postpartum): Dual prophylaxis with daily AZT + NVP for 12 weeks.
• Early Infant Diagnosis (EID) Testing Cascade:
  • HIV DNA PCR at birth (for high-risk infants).
  • HIV DNA PCR at 6 weeks of age (all HIV-exposed infants).
  • Repeat HIV DNA PCR at 6 months and 12 months.
  • Final confirmatory HIV antibody test at 18 months or 6 weeks after complete cessation of breastfeeding.