Huang Opportunistic Infections:

Introduction to Opportunistic Infections (OIs) in HIV\n- Course and Speaker Information: Presented by Vanthida Huang, PharmD, BSPHM, FCCP, FIDSA, FIDP. Professor of Pharmacy Practice, Biomedical Sciences, and Veterinary Medicine; Director of Infectious Diseases Translational Research Fellowship. Dates: May 7 & 11, $2026$.\n- Challenges in Reducing OI Incidence: Despite potent Antiretroviral Therapy (ART), OIs remain challenging because:\n - Undiagnosed HIV: Many individuals are unaware of their HIV status; approximately $21\%$ of those diagnosed in $2022$ had a CD4 T lymphocyte count < 200\,cells/mm^3 (or < 14\%\text{ percentage}) at the time of diagnosis, indicating advanced immunosuppression.\n - Care Linkage and Continuity: In $2022$, only $82\%$ of people newly diagnosed were linked to care within $1\,month$, and only $47\%$ were adequately engaged in continuous care.\n - Viral Suppression Rates: Only $65\%$ of people engaged in care in $2022$ achieved durable viral suppression. Failure is often due to adherence challenges, unfavorable pharmacokinetics, or unexplained biologic factors.\n- Correlation Between CD4 Count and Specific OIs:\n - CD4 < 500\,cells/mm^3: Tuberculosis (TB), Oropharyngeal Candidiasis (Oral Thrush).\n - CD4 < 200\,cells/mm^3: Pneumocystis jirovecii pneumonia (PCP), Esophageal Candidiasis.\n - CD4 < 100\,cells/mm^3: Toxoplasmosis, Cryptococcosis.\n - CD4 < 500\,cells/mm^3: Mycobacterium avium complex (MAC), Cytomegalovirus (CMV).\n- Primary vs. Secondary Prophylaxis:\n - Primary Prophylaxis: Prevents the first occurrence of a disease in at-risk individuals. Initiated based on immunosuppression levels (low CD4 counts).\n - Secondary Prophylaxis (Chronic Maintenance Therapy): Prevents relapse or recurrence of a disease the patient has previously had. Aims to avoid recurrence after successful control of the initial infection.\n\n# Pneumocystis jirovecii Pneumonia (PCP)\n- Epidemiology and Etiology:\n - Caused by ¨C14C. Reclassified as a fungus, though it shares biologic characteristics with protozoa.\n - Most common OI in people with HIV. Pre-ART, it occurred in $70-80\%$ of advanced cases.\n - Mortality rate: $20-40\%$.\n - Risk factors: CD4 count < 200\,cells/mm^3, CD4 percentage < 14\%, previous PCP episodes, oral thrush, recurrent bacterial pneumonia, unintentional weight loss, and high HIV RNA viral load.\n- ¨C15C:\n - Subacute onset of progressive dyspnea, fever, non-productive cough, and chest discomfort.\n - Physical findings: Observed exertion, tachycardia, diffuse dry rales. Fever is almost always present.\n- ¨C16C:\n - ¨C17C: \n - ¨C18C: room air arterial oxygen [PaO2] $\geq 70\,mmHg$ or alveolar-arterial (A-a) gradient < 35\,mmHg.\n - ¨C19C: A-a gradient $\geq 35\,mmHg$ to < 45\,mmHg.\n - ¨C20C: A-a gradient $\geq 45\,mmHg$.\n - ¨C21C: Elevated Lactate Dehydrogenase (LDH) levels > 500\,mg/dL (common but nonspecific). Elevated $1,3\,\beta\text{-D-glucan}$ (low specificity).\n - Radiology: Chest X-ray (CXR) shows diffuse, bilateral, symmetrical \u201cground-glass\u201d interstitial infiltrates in a butterfly pattern emanating from the hila. Spontaneous pneumothorax in HIV patients is highly suspicious of PCP. Chest CT shows patchy \u201cground-glass\u201d attenuation.\n - Definitive Diagnosis: Demonstration of organisms in tissue, bronchoalveolar lavage (BAL) fluid, or induced sputum samples via histopathology or cytopathology. PCR is sensitive but cannot distinguish colonization from active disease.\n- Primary Prophylaxis:\n - Indications: CD4 count $100-200\,cells/mm^3$ if HIV RNA is detectable, or CD4 count < 100\,cells/mm^3 regardless of HIV RNA.\n - Preferred Regimen: Trimethoprim-sulfamethoxazole (TMP-SMX/Bactrim DS) $1\,tab\,PO\,QD$. Alternative: Bactrim SS $1\,tab\,PO\,QD$.\n - Discontinuation: CD4 count increases from < 200\,cells/mm^3 to $\geq 200\,cells/mm^3$ for $\geq 3\,months$ in response to ART.\n - Restarting: If CD4 count falls below < 100\,cells/mm^3, or $100-200\,cells/mm^3$ with detectable HIV RNA.\n- Treatment Regimens:\n - Drug of Choice: TMP-SMX (Bactrim).\n - Moderate-Severe: $15-20\,mg/kg/day$ (TMP component) IV divided every $6-8\,hours$.\n - Mild-Moderate: $15-20\,mg/kg/day$ (TMP component) PO divided TID, or TMP-SMX DS $2\,tabs\,PO\,TID$.\n - Duration: $21\,days$.\n - Adjunctive Prednisone: Indicated for moderate-severe PCP (PaO2 < 70\,mmHg or A-a gradient $\geq 35\,mmHg$).\n - Prednisone Schedule: Days $1-5$ ($40\,mg\,PO\,BID$); Days $6-10$ ($40\,mg\,PO\,QD$); Days $11-21$ ($20\,mg\,PO\,QD$).\n - Methylprednisolone Schedule (IV): Days $1-5$ ($32\,mg\,BID$); Days $6-10$ ($32\,mg\,QD$); Days $11-21$ ($16\,mg\,QD$).\n- ¨C37C: Rash, photosensitivity, renal dysfunction (requires dose adjustment), bone marrow suppression (anemia, neutropenia, thrombocytopenia), hyperkalemia, and hepatotoxicity.\n\n# Toxoplasma gondii Encephalitis (TE)\n- ¨C38C: Caused by the protozoan ¨C39C. Usually a reactivation of latent tissue cysts. Greatest risk occurs when CD4 count is < 50\,cells/mm^3. Seroprevalence in the U.S. is approximately $11\%$. No person-to-person transmission.\n- ¨C40C:\n - ¨C41C: Subacute onset of headache, focal neurologic deficits (e.g., hemiparesis), and fever.\n - ¨C42C: Seizures, generalized headache.\n- ¨C43C:\n - ¨C44C: Positive anti-Toxoplasma IgG antibodies.\n - ¨C45C: Contrast-enhancing lesions (usually ring-enhancing) with a predilection for the basal ganglia. Can be single or multiple lesions.\n- ¨C46C:\n - ¨C47C: CD4 count < 100\,cells/mm^3 AND Toxoplasma IgG-positive.\n - ¨C48C: TMP-SMX DS $1\,tab\,PO\,QD$.\n - ¨C49C: Dapsone $50\,mg\,PO\,QD$ + (Pyrimethamine $50\,mg$ + Leucovorin $25\,mg$) weekly; Atovaquone $1500\,mg\,PO\,QD$.\n- ¨C50C:\n - ¨C51C: Pyrimethamine $200\,mg$ load $\times 1$, then weight-based ($50\,mg$ if $\leq 60\,kg$; $75\,mg$ if > 60\,kg) QD + Sulfadiazine ($1000\,mg$ if $\leq 60\,kg$; $1500\,mg$ if > 60\,kg) q6h + Leucovorin $10-25\,mg\,PO\,QD$.\n - Duration: At least $6\,weeks$.\n- Secondary Prophylaxis (Chronic Maintenance):\n - Pyrimethamine $25-50\,mg\,QD$ + Sulfadiazine $2000-4000\,mg\,PO\,daily$ (divided doses) + Leucovorin $10-25\,mg\,QD$. Can discontinue if successfully completed initial therapy, remains asymptomatic, and CD4 count > 200\,cells/mm^3 for > 6\,months on ART.\n- Adjunctive Therapy: Dexamethasone for mass effect or edema; antiseizure medications only if seizures occur (not for prophylaxis).\n- Adverse Events:\n - Pyrimethamine: Bone marrow suppression (reverse with Leucovorin), methemoglobinemia.\n - Sulfadiazine: Rash, fever, leukopenia, hepatitis, diarrhea.\n\n# Mycobacterium tuberculosis (TB)\n- Screening: All HIV patients must be evaluated for latent TB infection (LTBI) at diagnosis regardless of exposure history.\n- Latent TB Infection (LTBI) Treatment:\n - Indication: Screen positive for LTBI, no active disease, or close contact with an infectious person regardless of CD4/screening results.\n - Preferred (3HP Regimen): Isoniazid (INH) $15\,mg/kg\,PO\,weekly$ (max $900\,mg$) + Rifapentine (weight-based) weekly + Pyridoxine $50\,mg\,weekly\,x\,12\,weeks$. Only for virally-suppressed patients on specific ART (efavirenz, raltegravir, or once-daily dolutegravir).\n - Preferred Alternate: INH $300\,mg\,PO\,QD$ + Pyridoxine $25-50\,mg\,PO\,QD\,x\,3\,months$.\n\n# Mycobacterium avium complex (MAC)\n- Epidemiology: Ubiquitous in environment; transmitted via inhalation or ingestion. Disseminated MAC occurs in $20-40\%$ of HIV patients with CD4 < 50\,cells/mm^3 in the absence of therapy.\n- Presentation: Nonspecific symptoms (fever, night sweats, weight loss, diarrhea, fatigue). Labs show anemia and elevated alkaline phosphatase. Physical findings: hepatomegaly, splenomegaly, lymphadenopathy.\n- Diagnosis: Isolation of MAC from cultures of blood, lymph fluid, bone marrow, or sterile body fluids (slow-growing).\n- Primary Prophylaxis:\n - Indication: CD4 count < 50\,cells/mm^3 AND patient is not receiving ART or remains viremic on ART. Not recommended for those immediately starting ART.\n - Preferred: Azithromycin $1200\,mg\,PO\,once\,weekly$. Alternative: Clarithromycin $500\,mg\,PO\,BID$.\n- Treatment (Preferred Regimen):\n - Clarithromycin $500\,mg\,PO\,BID$ + Ethambutol $15\,mg/kg\,PO\,QD$.\n - Duration: At least $12\,months$.\n- Secondary Prophylaxis and Discontinuation: Maintain on treatment drugs. Discontinue after $12\,months$ of therapy if asymptomatic and CD4 count has been > 100\,cells/mm^3 for $\geq 6\,months$ in response to ART.\n- Immune Reconstitution Inflammatory Syndrome (IRIS): Manage moderate-severe IRIS with NSAIDs or short-term systemic corticosteroids (Prednisone $20-40\,mg\,x\,4-8\,weeks$).\n\n# Oropharyngeal and Esophageal Candidiasis\n- Etiology: Primarily Candida albicans. Esophageal candidiasis is an AIDS-defining illness.\n- Presentation:\n - Oropharyngeal (Thrush): Painless white plaques on the tongue, gums, or palate that can be easily scraped off.\n - Esophageal: Retrosternal burning pain, odynophagia. Diagnosed by symptoms/therapeutic response or endoscopy (white plaques).\n- Primary Prophylaxis: Routine prophylaxis is not recommended due to resistance concerns and low mortality.\n- Treatment:\n - Oropharyngeal: Fluconazole $200\,mg$ load then $100-200\,mg\,PO\,QD$ for $7-14\,days$. Alternatives: Miconazole buccal tab, Clotrimazole troches, or Nystatin suspension.\n - Esophageal: Fluconazole $200\,mg$ load then $100-200\,mg$ (up to $400\,mg$) PO/IV QD for $14-21\,days$.\n\n# Cryptococcus neoformans (Cryptococcosis)\n- Epidemiology: Caused by Cryptococcus neoformans (rarely C. gattii). $90\%$ of cases occur at CD4 < 100\,cells/mm^3. Accounts for $15\%$ of AIDS-related deaths globally.\n- Presentation: Fever, malaise, headache. Menigial signs (neck stiffness, photophobia) in $25-33\%$ of patients. Encephalopathic symptoms (lethargy, memory loss) due to increased intracranial pressure (ICP).\n- Diagnosis: CSF analysis for culture, Gram strain/India ink, or Cryptococcal antigen (CrAg). CrAg can also be detected in blood.\n- Treatment Phases:\n - Induction (2 weeks): Liposomal amphotericin B $3-4\,mg/kg\,IV\,QD$ + Flucytosine $25\,mg/kg\,PO\,QID$.\n - Consolidation (\u22658 weeks): Fluconazole $800\,mg\,PO\,QD$. If CSF is still positive after induction, continue $800\,mg$ or increase to $1200\,mg\,QD$ until sterile.\n - Maintenance (\u22651 year): Fluconazole $200\,mg\,PO\,QD$.\n\n# Cytomegalovirus (CMV) Retinitis\n- Epidemiology: Herpesvirus family infection. Occurs at CD4 < 50\,cells/mm^3. Most common manifestation of end-organ CMV disease in HIV.\n- Presentation: Usually unilateral (2/3 of cases). Full-thickness necrotizing retinal infection: fluffy, yellow-white lesions. Symptoms include floaters, scotomata (dark spots), and visual field defects. Can lead to blindness if untreated.\n- Treatment Regimens:\n - Induction (14-21 days): Valganciclovir $900\,mg\,PO\,q12h$ or Ganciclovir $5\,mg/kg\,IV\,q12h$.\n - Maintenance: Valganciclovir $900\,mg\,PO\,QD$.\n - Alternatives: Foscarnet ($60\,mg/kg\,q8h$ or $90\,mg/kg\,q12h$) or Cidofovir ($5\,mg/kg$ weekly for $2\,weeks$, then biweekly).\n- Drug Considerations:\n - Valganciclovir/Ganciclovir: Bone marrow suppression is a key side effect; requires renal adjustment.\n - Foscarnet/Cidofovir: Black Box Warning for renal toxicity. Electrolyte disorders and anemia are common with Foscarnet.", "title": "Study Notes on HIV-Associated Opportunistic Infections: Prevention, Prophylaxis, and Treatment"}