7.3 HIV/AIDS Management, Antiretroviral Therapy (ART) & Opportunistic Infections

7.3 HIV/AIDS Management, Antiretroviral Therapy (ART) & Opportunistic Infections

Quick Answer: Human Immunodeficiency Virus (HIV) infection is a chronic retroviral disease characterized by progressive destruction of CD4+ T-helper lymphocytes, culminating in profound cell-mediated immunodeficiency and acquired immunodeficiency syndrome (AIDS). In Ghana, HIV testing services follow the "5 Cs" (Consent, Confidentiality, Counselling, Correct results, Connection to care) using a serial rapid diagnostic algorithm. Under the Ghana National AIDS/STI Control Programme (NACP) "Test and Treat" policy, all individuals confirmed positive initiate lifelong Antiretroviral Therapy (ART) immediately, regardless of CD4 cell count or WHO clinical stage. The preferred first-line regimen is the once-daily fixed-dose combination TLD (Tenofovir Disoproxil Fumarate + Lamivudine + Dolutegravir). Key priorities include proactive toxicity monitoring, Option B+ PMTCT execution, timely prophylaxis against Pneumocystis jirovecii pneumonia, and vigilant management of opportunistic infections to prevent fatal Immune Reconstitution Inflammatory Syndrome (IRIS).

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Virology, Transmission, and Pathophysiology

HIV belongs to the genus Lentivirus within the family Retroviridae. Two major types infect humans: HIV-1, distributed globally with high pathogenicity and transmission efficiency, and HIV-2, concentrated largely in West Africa (including Ghana). HIV-2 is characterized by lower plasma viral loads, slower CD4 decline, lower rates of vertical transmission, and intrinsic structural resistance to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs).

                         THE HIV REPLICATION CYCLE
                                     |
   1. ATTACHMENT & BINDING: Viral gp120 binds CD4 receptor
      + chemokine co-receptor (CCR5 or CXCR4)
                                     |
   2. FUSION & ENTRY: gp41 conformational change mediates
      viral envelope fusion with host cell membrane
                                     |
   3. REVERSE TRANSCRIPTION: Viral RNA converted to double-stranded
      cDNA via Reverse Transcriptase (Target of NRTIs & NNRTIs)
                                     |
   4. INTEGRATION: Viral cDNA transported to nucleus and spliced
      into human genome by Integrase enzyme (Target of INSTIs like DTG)
                                     |
   5. TRANSCRIPTION & TRANSLATION: Host RNA polymerase transcribes
      proviral DNA into viral mRNA and polyprotein precursors
                                     |
   6. ASSEMBLY: Core proteins, viral genomic RNA, and enzymes
      package beneath host plasma membrane
                                     |
   7. BUDDING & MATURATION: Immature virion buds off; viral Protease
      cleaves polyproteins to form mature infectious virion (Target of PIs)

Cellular Pathogenesis and CD4 Depletion

The viral envelope surface glycoprotein gp120 binds with high affinity to the primary CD4 receptor expressed on T-helper lymphocytes, monocytes, macrophages, and dendritic cells. This induces a conformational shift allowing gp120 to bind a chemokine co-receptor—either CCR5 (macrophage-tropic, predominant during early transmission) or CXCR4 (T-cell tropic, emerging during late disease). Transmembrane glycoprotein gp41 then mediates membrane fusion, releasing the viral capsid containing two identical single-stranded RNA molecules and viral enzymes (reverse transcriptase, integrase, protease) into the host cytoplasm.

Following integration into the host genome, HIV establishes a lifelong proviral state. Progressive depletion of CD4+ T-helper cells occurs through direct viral cytolysis, syncytium formation, apoptosis of uninfected bystander cells, and CD8+ cytotoxic T-lymphocyte destruction of infected cells. When CD4+ counts fall below critical thresholds, cell-mediated immunity fails, permitting reactivation of latent pathogens and fatal opportunistic malignancies.

Transmission Routes in Ghana

• Unprotected Heterosexual Intercourse: Accounts for over 80% of infections in Ghana.
• Mother-to-Child Transmission (MTCT): Occurs during pregnancy (antepartum), labor and delivery (intrapartum), or through breastfeeding (postpartum).
• Parenteral / Percutaneous Inoculation: Unscreened blood transfusions, contaminated needle reuse, and accidental occupational sharps injuries.

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WHO Clinical Staging System (Stages 1 through 4)

The WHO staging framework categorizes clinical disease severity to guide clinical decisions, evaluate prognosis, and determine opportunistic infection risks:

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Testing Modalities & Ghana National Testing Algorithm

HIV testing in Ghana is executed via Provider-Initiated Testing and Counselling (PITC) in all health facilities and Voluntary Counselling and Testing (VCT) in community centers, anchored strictly to the 5 Cs:

1. Consent: Verbal informed consent; patients maintain the right to decline (opt-out approach).
2. Confidentiality: Results shared solely between patient and healthcare team.
3. Counselling: Pre-test information and comprehensive post-test counselling.
4. Correct Results: Adherence to strict quality-controlled testing algorithms.
5. Connection to Care: Immediate active linkage to ART initiation on the same day.

Ghana Serial Rapid Testing Algorithm

Ghana uses a nationally validated serial algorithm of rapid tests (the specific kits change with national procurement and are listed in the current national testing guidelines):

                     GHANA SERIAL RAPID TESTING ALGORITHM
                                      |
                      [TEST 1: SCREENING ASSAY]
                      (first approved kit)
                                      |
                     +----------------+----------------+
                     |                                 |
                NON-REACTIVE                        REACTIVE
                     |                                 |
               REPORT NEGATIVE              [TEST 2: CONFIRMATORY ASSAY]
                                                (second approved kit)
                                                       |
                                      +----------------+----------------+
                                      |                                 |
                                   REACTIVE                        NON-REACTIVE
                                      |                            (DISCORDANT)
                               REPORT POSITIVE                          |
                            (Specify HIV-1, HIV-2,              [TEST 3: TIE-BREAKER]
                                  or Dual)                           (third kit)
                                                                        |
                                                       +----------------+----------------+
                                                       |                                 |
                                                    REACTIVE                        NON-REACTIVE
                                                       |                                 |
                                                REPORT POSITIVE                  REPORT INCONCLUSIVE
                                                                                 (Retest in 14 days)

• Test 1 (Screening Assay): High-sensitivity assay (first approved kit). If non-reactive, the client is confirmed HIV Negative (counsel on window period if recent exposure occurred).
• Test 2 (Confirmatory Assay): If Test 1 is reactive, perform a high-specificity confirmatory assay (second approved kit). If both tests are reactive, report HIV Positive and differentiate type (HIV-1, HIV-2, or dual infection).
• Test 3 (Tie-Breaker Assay): If Test 1 is reactive but Test 2 is non-reactive (discordant result), run a third assay (third kit). If Test 3 is reactive, report HIV Positive. If Test 3 is non-reactive, report Inconclusive; instruct client to return in 14 to 28 days for a repeat test to resolve possible seroconversion window period dynamics.

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Ghana ART Guidelines: "Test and Treat" & First-Line Regimens

Under the Ghana NACP guidelines, Ghana implements a universal "Test and Treat" policy: all children, adolescents, and adults confirmed to be living with HIV must be initiated on lifelong Antiretroviral Therapy (ART) immediately—preferably on the same day as diagnosis, and no later than 7 days—regardless of CD4 cell count or clinical staging, provided clinical stability is confirmed.

Preferred Adult First-Line Regimen: TLD Single-Tablet Combination

The preferred first-line regimen for adults, adolescents, and women of childbearing potential is a once-daily fixed-dose combination tablet consisting of:

• Tenofovir Disoproxil Fumarate (TDF) 300 mg: Nucleotide Reverse Transcriptase Inhibitor (NtRTI)
• Lamivudine (3TC) 300 mg: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
• Dolutegravir (DTG) 50 mg: Integrase Strand Transfer Inhibitor (INSTI)

Advantages of Dolutegravir (DTG)-Based Regimens

Dolutegravir has superseded Efavirenz (EFV) due to its high genetic barrier to resistance, rapid achievement of plasma viral suppression (typically within 4 to 8 weeks), once-daily administration, low incidence of adverse effects, and absence of cross-resistance to first-generation NNRTIs.

Alternative Regimens

• In patients with pre-existing renal impairment (eGFR $< 50\text{ mL/min}$): Substitute TDF with Abacavir (ABC), yielding ABC + 3TC + DTG.
• If DTG is unavailable or contraindicated: Use TDF + 3TC + Efavirenz (EFV 400 mg).

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Drug Toxicities & Pharmacovigilance

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Prevention of Mother-to-Child Transmission (PMTCT: Option B+)

Without intervention, the risk of vertical transmission ranges from 15% to 45%. With full PMTCT implementation, transmission drops below 2% in non-breastfeeding populations and below 5% in breastfeeding populations.

1. Option B+ Maternal Strategy: Every pregnant or breastfeeding woman diagnosed with HIV is immediately initiated on lifelong TLD fixed-dose combination, irrespective of CD4 cell count, gestational age, or clinical stage. ART must be continued uninterrupted through pregnancy, labor, delivery, breastfeeding, and for life.
2. Labor & Delivery Safeguards: Practice universal precautions; avoid prolonged rupture of membranes (> 4 hours); avoid invasive procedures including artificial rupture of membranes (ARM), fetal scalp electrodes, and routine episiotomy; gently wipe infant mouth and nose clear of maternal blood and secretions immediately upon delivery.
3. Infant Post-Exposure Prophylaxis (PEP): Administer daily oral Nevirapine (NVP) syrup to the newborn starting within 72 hours of birth (preferably within 4 hours) and continued daily for 6 weeks for standard-risk infants. If the mother had a viral load $> 1{,}000\text{ copies/mL}$ at delivery or was on ART for $< 4\text{ weeks}$, extend infant prophylaxis to 12 weeks with dual therapy (Nevirapine + Zidovudine).
4. Infant Feeding Guidance in Ghana: Mothers receiving ART and virally suppressed are encouraged to practice exclusive breastfeeding for the first 6 months, followed by introducing safe complementary foods while continuing breastfeeding up to 12 to 24 months. Mixed feeding (breastmilk combined with formula or other liquids) in the first 6 months is strictly avoided, as foreign proteins disrupt mucosal integrity and dramatically increase HIV transmission.
5. Early Infant Diagnosis (EID) Protocol: Maternal IgG antibodies cross the placenta, persisting in infant circulation up to 18 months; therefore, rapid antibody tests produce false positives. Definitive infant diagnosis requires direct detection of viral genetic material via HIV DNA Polymerase Chain Reaction (PCR):
   • First Test: At 4 to 6 weeks of age (or first clinical contact).
   • Second Test: At 9 months of age.
   • Final Confirmatory Test: 6 weeks after complete cessation of breastfeeding (using rapid antibody test if child is $\ge 18\text{ months}$). If any DNA PCR is positive, confirm with a second sample and immediately initiate pediatric ART.

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Opportunistic Infections & Immune Reconstitution Inflammatory Syndrome (IRIS)

[!CAUTION] Immune Reconstitution Inflammatory Syndrome (IRIS): Following ART initiation, vigorous restoration of pathogen-specific cellular immunity can provoke an exaggerated inflammatory response against residual antigens of treated or occult infections (most commonly M. tuberculosis or Cryptococcus). Manifestations include high fevers, worsening lymphadenopathy, and enlarging intracranial lesions. Management requires continuing ART, treating the underlying opportunistic pathogen aggressively, and administering systemic corticosteroids in life-threatening inflammatory states.