4.8 Opportunistic Infections & Sexually Transmitted Infections
Key Takeaways
- Urethritis, genital ulcers, vulvovaginitis, cervicitis, epididymitis, syphilis and human papillomavirus are enumerated under sexually transmitted diseases.
- Prophylaxis against Pneumocystis begins below a CD4 count of 200 cells per microliter and against Mycobacterium avium complex historically below 50.
- Adjunctive corticosteroids are indicated in Pneumocystis pneumonia when the arterial oxygen tension is below 70 mmHg or the alveolar-arterial gradient exceeds 35 mmHg.
- Neurosyphilis is treated with intravenous penicillin G rather than intramuscular benzathine penicillin, and penicillin-allergic patients require desensitization.
- Immune reconstitution inflammatory syndrome is an enumerated blueprint topic and represents paradoxical worsening after antiretroviral initiation rather than treatment failure.
Last updated: August 2026
1. Opportunistic Infections (OIs) Stratified by CD4 Count
A. CD4 < 200 cells/mcL (or CD4% < 14%)
Pneumocystis jirovecii Pneumonia (PJP / PCP)
- Clinical Presentation: Subacute onset (over 2–4 weeks) of progressive exertional dyspnea, non-productive dry cough, low-grade fever, hypoxemia, and markedly elevated serum Lactate Dehydrogenase (LDH >500 IU/L). Chest radiography/CT shows bilateral diffuse, symmetric interstitial/perihilar ground-glass opacities.
- Primary Prophylaxis: Indicated when CD4 < 200 cells/mcL or history of oral candidiasis (thrush). First-line: Trimethoprim-sulfamethoxazole (TMP-SMX) 1 Double-Strength (DS) tab PO daily (or 1 Single-Strength tab daily). Alternatives for severe sulfa allergy: Dapsone (100 mg daily; check G6PD first), Atovaquone (1500 mg daily), or monthly aerosolized Pentamidine (300 mg). Discontinue when CD4 >200 cells/mcL for >=3 months on ART.
- Acute Treatment: High-dose TMP-SMX (15–20 mg/kg/day of TMP component IV or PO divided q6–8h for 21 days).
- Mandatory Adjunctive Corticosteroids: Initiate IV/PO Prednisone (40 mg BID x 5 days, 40 mg daily x 5 days, then 20 mg daily x 11 days) before or concurrently with antimicrobial therapy IF:
- Room air arterial PaO2 < 70 mmHg, OR
- Alveolar-Arterial (A-a) oxygen gradient >= 35 mmHg.
- Mechanism: Prevents severe inflammatory lung injury and respiratory failure triggered by dying Pneumocystis organisms.
B. CD4 < 100 cells/mcL
Toxoplasma gondii Encephalitis
- Clinical Presentation: Subacute headache, confusion, focal neurological deficits (hemiparesis, cranial nerve palsies), and seizures. MRI brain reveals multiple ring-enhancing lesions with surrounding vasogenic edema, with a predilection for the basal ganglia and gray-white junction.
- Primary Prophylaxis: TMP-SMX 1 DS tab daily in patients who are Toxoplasma IgG seropositive with CD4 < 100 cells/mcL (standard PJP prophylaxis provides dual coverage).
- Acute Treatment: Pyrimethamine + Sulfadiazine + Leucovorin (folinic acid) for 6 weeks. (Leucovorin is mandatory to prevent pyrimethamine-induced bone marrow suppression). Alternative: Pyrimethamine + Clindamycin + Leucovorin.
Cryptococcal Meningitis (Cryptococcus neoformans)
- Clinical Presentation: Subacute indolent headache, fever, malaise, cranial neuropathies (CN VI diplopia), and elevated intracranial pressure (papilledema, lethargy).
- Diagnostics: Lumbar puncture demonstrates elevated opening pressure (>200 mm H2O in >75% of cases), positive CSF Cryptococcal Antigen (CrAg) titer (>98% sensitivity/specificity), positive India ink stain (encapsulated budding yeasts), and lymphocytic pleocytosis with low glucose.
- Three-Phase Management Strategy:
- Induction Phase (Minimum 2 weeks): Liposomal Amphotericin B (3–4 mg/kg IV daily) PLUS Flucytosine (100 mg/kg/day PO divided q6h) until clinical improvement and documented CSF fungal clearance.
- Consolidation Phase (Minimum 8 weeks): High-dose Fluconazole (400–800 mg PO daily).
- Maintenance Phase: Fluconazole (200 mg PO daily) for at least 1 year (discontinue once CD4 >100 for >=3 months on ART with undetectable viral load).
- Intracranial Pressure (ICP) Control: Perform serial daily therapeutic lumbar punctures to remove CSF and maintain opening pressure <200 mm H2O (or reduce by 50% if opening pressure >400 mm H2O). Lumbar drains or VP shunts are indicated for refractory intracranial hypertension. (Steroids, mannitol, and acetazolamide are contraindicated).
- Timing of ART Initiation: Delay ART for 2 to 6 weeks after starting antifungal therapy to prevent life-threatening CNS Immune Reconstitution Inflammatory Syndrome (IRIS).
C. CD4 < 50 cells/mcL
Mycobacterium avium Complex (MAC)
- Clinical Presentation: Disseminated multiorgan disease presenting with constitutional symptoms (hectic fevers, drenching night sweats, profound weight loss, fatigue), abdominal pain, chronic diarrhea, hepatosplenomegaly, severe anemia, and markedly elevated serum alkaline phosphatase. Blood cultures for acid-fast bacilli (AFB) confirm diagnosis.
- Primary Prophylaxis: Primary prophylaxis with Azithromycin is NO LONGER routinely recommended in individuals with HIV who immediately initiate effective ART, regardless of CD4 count.
- Treatment: Clarithromycin (500 mg PO BID) or Azithromycin (500 mg PO daily) PLUS Ethambutol (15 mg/kg PO daily) for at least 12 months.
Cytomegalovirus (CMV) Retinitis
- Clinical Presentation: Painless blurred vision, floaters, photopsia (flashing lights), and progressive visual field scotomas. Funduscopy reveals the pathognomonic "pizza-pie" or "brushfire" appearance: confluent yellowish-white retinal necrotic infiltrates with perivascular retinal hemorrhages.
- Treatment: Oral Valganciclovir (900 mg PO BID x 14–21 days induction, then 900 mg daily maintenance) OR IV Ganciclovir. Immediate intravitreal ganciclovir/foscarnet injections are added for sight-threatening lesions involving or adjacent to the macula or optic nerve.
2. Sexually Transmitted Infections (STIs)
Syphilis (Treponema pallidum)
| Stage | Clinical Manifestations & Diagnostic Features | Recommended Treatment Regimen |
|---|---|---|
| Primary Syphilis | • Solitary, painless, indurated ulcer (chancre) with a clean base and raised, firm margins<br/>• Non-tender, rubbery regional inguinal lymphadenopathy (heals spontaneously in 3–6 weeks) | Benzathine Penicillin G 2.4 million units IM as a single dose |
| Secondary Syphilis | • Disseminated stage occurring 4–10 weeks after chancre<br/>• Symmetric, non-pruritic maculopapular rash involving the palms and soles<br/>• Condylomata lata (broad, moist, flat, highly infectious plaques in intertriginous/perianal regions)<br/>• Mucous patches, "moth-eaten" alopecia, generalized lymphadenopathy, constitutional symptoms | Benzathine Penicillin G 2.4 million units IM as a single dose |
| Early Latent Syphilis | • Asymptomatic infection acquired within the preceding < 1 year (documented by seroconversion or known exposure) | Benzathine Penicillin G 2.4 million units IM as a single dose |
| Late Latent Syphilis / Latent of Unknown Duration | • Asymptomatic infection acquired > 1 year ago or duration entirely unknown | Benzathine Penicillin G 2.4 million units IM weekly for 3 consecutive doses (total 7.2 million units) |
| Tertiary Syphilis | • Gummatous syphilis (destructive nodular/granulomatous lesions of skin and bones)<br/>• Cardiovascular syphilis (ascending aortic aneurysm, aortic regurgitation, "tree-bark" aortitis) | Benzathine Penicillin G 2.4 million units IM weekly for 3 consecutive doses (total 7.2 million units) |
| Neurosyphilis / Ocular / Otosyphilis | • Can occur at ANY stage of syphilis<br/>• Meningovascular stroke, tabes dorsalis (ataxia, lancinating pains, loss of vibration/proprioception, Argyll Robertson pupils [accommodate to near vision but do not react to light]), general paresis (dementia, psychosis), uveitis, sensorineural hearing loss | Aqueous Crystalline Penicillin G 18 to 24 million units/day IV (administered as 3–4 million units IV every 4 hours or continuous infusion) for 10 to 14 days |
High-Yield Syphilis Management Pearls
- Serologic Monitoring: Non-treponemal titers (RPR or VDRL) are used to monitor treatment response. A 4-fold decline in titer (e.g., from 1:32 down to 1:8) at 6 to 12 months indicates successful therapy.
- Jarisch-Herxheimer Reaction: Acute, benign, self-limiting febrile reaction (fevers, rigors, headache, tachycardia, transient exacerbation of rash) occurring within 2 to 24 hours after the first dose of penicillin. Caused by massive spirochetal lysis releasing pyrogenic endotoxins. Managed supportively with antipyretics (acetaminophen); do not stop penicillin.
- Penicillin Allergy in Pregnancy: Penicillin is the only proven therapy effective for treating maternal syphilis and preventing congenital syphilis. Pregnant patients with documented penicillin allergy MUST undergo penicillin skin testing and oral desensitization, followed by treatment with Benzathine Penicillin G. (Doxycycline is strictly contraindicated in pregnancy).
Gonorrhea & Chlamydia (CDC 2021 Treatment Guidelines)
- Uncomplicated Urogenital, Anorectal, or Pharyngeal Gonorrhea (Neisseria gonorrhoeae):
- Ceftriaxone 500 mg IM single dose (for body weight <150 kg; administer 1,000 mg IM if body weight >=150 kg).
- Note: Azithromycin 1 g is NO LONGER co-administered with ceftriaxone due to widespread macrolide resistance.
- Chlamydia Trachomatis (Chlamydia trachomatis):
- Doxycycline 100 mg PO twice daily for 7 days (first-line regimen; superior microbiological cure rates compared to single-dose azithromycin, especially for rectal chlamydia).
- Alternative for pregnancy: Azithromycin 1 g PO as a single dose.
- Empiric Co-Treatment Rule: If N. gonorrhoeae is diagnosed via NAAT and C. trachomatis infection has not been ruled out, administer Ceftriaxone 500 mg IM single dose PLUS Doxycycline 100 mg PO BID for 7 days.
Test Your Knowledge
A 34-year-old man with newly diagnosed HIV infection presents to the emergency department with a 3-week history of progressive exertional shortness of breath, dry non-productive cough, and fever. On examination, his temperature is 38.6°C (101.5°F), respiratory rate is 28 breaths/min, heart rate is 104 bpm, and oxygen saturation is 84% on room air. Arterial blood gas (ABG) on room air reveals: pH 7.46, PaCO2 30 mmHg, and PaO2 54 mmHg (calculated Alveolar-Arterial oxygen gradient: 48 mmHg). Laboratory studies show a CD4 count of 68 cells/mcL and serum LDH of 620 IU/L. Chest radiography demonstrates bilateral diffuse symmetric perihilar ground-glass interstitial opacities. Which of the following is the most appropriate initial pharmacological regimen for this patient?
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D
Test Your Knowledge
A 48-year-old man presents with progressive memory impairment, personality changes, unsteadiness when walking in the dark, and sharp, shooting pains in his legs. On physical examination, he has bilateral loss of vibratory and position sense in the lower extremities and a wide-based sensory ataxic gait. Pupillary examination reveals small, irregular pupils that constrict briskly when focusing on a near target but fail to constrict when exposed to direct light. Serum RPR is reactive at a titer of 1:64, and serum Treponema pallidum particle agglutination (TP-PA) is reactive. Lumbar puncture reveals a CSF WBC count of 35/mcL (94% lymphocytes), protein of 85 mg/dL, and a reactive CSF-VDRL. What is the most appropriate treatment for this patient?
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D