Pharmacotherapy of Opportunistic Infections

Pharmacotherapy of Opportunistic Infections

1. Definition, immunological setting and the CD4 map

• An opportunistic infection (OI) is an intercurrent infection by an organism that is ordinarily innocuous in an immunocompetent host but becomes invasive and often lethal once cell-mediated immunity fails; in people living with HIV (PLHIV) the susceptible spectrum spans protozoa, fungi, viruses and bacteria (NACO 2021 §2.9.1, p.145).
• OIs remain the major cause of morbidity and mortality among PLHIV, and their occurrence corresponds closely to the falling CD4⁺ T-lymphocyte count — the single most useful pharmacotherapeutic trigger in this topic (NACO 2021 §2.9.1, p.145).
• The natural-history rationale: after seroconversion the plasma HIV-RNA settles to a set point, the CD4⁺ count then declines steadily, and once the peripheral CD4 count falls below 200 cells/mm³ there is an increasing risk of opportunistic diseases and, ultimately, death (G&G 14e Ch.64, p.1246).
• Median time from sexual acquisition of CCR5-tropic HIV-1 to clinical AIDS is 8–10 years untreated; long-term nonprogressors harbour HIV for >2 decades without CD4 decline, reflecting favourable host immunogenetics (G&G 14e Ch.64, p.1246).
• CD4-stratified OI map (NACO 2021, Fig 2.9.1, p.145) — this is the scaffold on which every prophylaxis decision in this chapter hangs:
  • CD4 ≈ 350–500/mm³ — herpes zoster
  • CD4 ≈ ≤350/mm³ — tuberculosis
  • CD4 ≈ ≤250/mm³ — oral candidiasis
  • CD4 ≈ <200/mm³ — PCP, oesophageal candidiasis, mucocutaneous herpes
  • CD4 ≈ <100/mm³ — toxoplasmosis, cryptococcosis, cryptosporidiosis, PML
  • CD4 ≈ <50/mm³ — CMV, disseminated MAC
• Disseminated MAC specifically occurs in patients with CD4 <50 cells/mm³ who are not on antiretroviral therapy (ART); M. avium is the commonest infecting species in this population (G&G 14e Ch.65, p.1281; NACO 2021 §4.3.4, p.334).
• KDT frames the same physiology: as the CD4 population declines markedly, cell-mediated immunity is lost and "opportunistic infections abound", to which the AIDS patient ultimately succumbs (KDT 8e Ch.60, p.861).
• KDT further notes the Indian burden context — a high background prevalence of both tuberculosis and Mycobacterium avium complex (MAC) infection among HIV-infected patients in India, which shifts the empirical weighting of Indian OI practice towards mycobacterial disease (KDT 8e Ch.56, p.817).
• Why fungi and viruses dominate the OI list pharmacologically: fungi are eukaryotes, so selective toxicity is intrinsically hard and the exploitable differences are few — membrane ergosterol biosynthesis, the fungal ability to deaminate cytosine, and the unique glucan/chitin cell wall. The incidence of life-threatening fungal infection has risen precisely because immunocompromised populations (transplant, chemotherapy, immunosuppressants, HIV-AIDS) have expanded (G&G 14e Ch.61, p.1193).
• Mortality from invasive fungal disease remains unacceptably high despite the modern antifungal pharmacopeia — the pharmacological justification for combination induction regimens in cryptococcosis (G&G 14e Ch.61, p.1193).

Terminology used throughout this chapter

• Primary prophylaxis / primary prevention — a prophylactic drug given before any episode of that OI has occurred (NACO 2021 §2.9.2, p.146).
• Secondary prophylaxis / maintenance therapy / chronic maintenance therapy — a drug continued after successful completion of treatment of an episode, to prevent recurrence (NACO 2021 §2.9.2, p.146).
• Pre-emptive therapy — full-dose antifungal or antiviral therapy given to an asymptomatic patient who has a positive laboratory marker of subclinical infection (e.g. serum cryptococcal antigen, CMV viraemia) (NACO 2021 §4.2.2, pp.293–4; G&G 14e Ch.62, p.1217).
• Induction → consolidation → maintenance — the three-phase architecture of cryptococcal (and, functionally, CMV) therapy: a short, intensive, fungicidal/virucidal induction; a longer, oral, sterilising consolidation; then low-dose suppression until immune reconstitution (NACO 2021 Table 4.2.5, p.295).
• IRIS — immune reconstitution inflammatory syndrome; a paradoxical inflammatory deterioration on starting ART (G&G 14e Ch.64, p.1247; NACO 2021 §2.2, pp.43–6).