RNA to DNA, causing nonfunctional DNA. Purine Analogues: Abacavir (ABC) Tenofovir (TDF or TAF) Didanosine TDF: Renal and bone adverse effects. Fanconi syndrome. Favorable Lipids. Didanosine: Pancreatitis; peripheral neuropathy, lipoatrophy, lactic acidosis Non-Nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs) Also inhibit reverse transcriptase, but do so by binding directly to reverse transcriptase Efavirenz (EFV) Rilpivirine Nevirapine Etravirine Efavirenz: Neuropsychiatric effects, rash in 15% of pts Rilpivirine: Cannot take with PPIs Nevirapine: Hypersensitivity; hepatotoxicity Etravirine: Rash Protease Inhibitors (PI) Prevents protease from cleaving HIV proteins and enzymes into forms that can infect other cells. Darunavir Atazanavir Ritonavir Fosamprenavir Indinavir Lopinavir Nelfinavir Saquinavir Tipranavir Atazanavir: Hyperbilirubinemia; nephrolithiasis Indinavir: Lipoaccumulation Saquinavir: Lipoaccumulation All PIs may cause the metabolic syndrome Integrase Inhibitors Block HIV integrase, which encorporates HIV DNA into host DNA Raltegravir Elvitegravir (EVG) Dolutegravir (DTG) Dolutegravir: Caution when used with metformin; May elevate serum creatinine; New data suggests may increase risk of neural tubes defects if taken during pregnancy. Booster Agents Inhibit CYP 3A4, increasing concentrations of other HIV drugs (notably PIs) Ritonavir (also a PI itself) Cobicistat Cobicistat: May increase serum creatinine Drug-Drug interactions may occur, notably with commonly prescribed medications such as statins, NOACs, and steroids (inhaled and systemic) Note: Entry Inhibitors that block attachment of HIV to host cells, including Enfuvirtide and Maraviroc, have a limited role in therapy and are now rarely used because of method of delivery (injection) and side effects.
Important Opportunistic Infections: Pathogen CD4 Count Common Presentation Tests Prophylaxis/Treatment Pneumocystis jirovecci Pneumonia (PCP) <200 (or Dry Cough, Dyspnea on Exertion, Fever. Tends to have sub-acute course. CXR: Diffuse bilateral infiltrates. May lead to respiratory failure, pneumothorax, and death (still common cause of AIDS-related death) - PCP DFA (from Sputum or BAL) - Cytopathology from BAL - Elevated serum (1,3) B-D-Glucan PPx: Bactrim 160-800 daily Alternate: Dapsone, atovaquone Tx: Bactrim x 21 days Alternate: Atovaquone (mild); Clindamycin/ primaquine (moderate); IV Pentamidine (severe. + Steroids for moderate – severe PCP (PaO2 < 70 or gradient > 35) Mycoacterium Avium Complex (MAC) (MAC = water and soil mycobacteria) <50 Prolonged course of fever. Fatigue, weight loss, diarrhea. Hepatosplenomegaly. Culture from a sterile site (eg: blood, bone marrow, lymph node) Ppx: Azithromycin 1200 mg weekly Alternate: Clarithromycin Tx: Macrolide + Ethambutol +/- Rifabutin Toxoplasma gondii <100 Usually presents with signs of CNS disease (eg: encephalitis – headache/fever/confusion. May have seizures and/or altered mental status) Posterior Uveitis Pneumonitis (rare): fever/cough/dyspnea Presumptive dx: compatible clinical syndrome, + T. gondii IgG Ab and classic imaging findings (multiple lesions) PPx: Bactrim 160-800 daily Tx: Bactrim, sulfadiazine/pyramethamine Alternate Tx: Regimens containing Atovaquone,or Clindamycin instead of Sulfadiazine
Progressive Multifocal Leukoencephalopathy (PML) (JC virus – a human papylomavirus – reactivates and infects oligodendrocytes and astrocytes) Mostly < 150 Insidious progression (over weeks) of focal neurological deficits 2/2 patchy demyelinating process. Symptoms may include: AMS, motor deficits, limb ataxia, gait ataxia, visual symptoms, seizures. Diagnosis made on clinical presentation and CT/MRI findings showing multifocal areas of white matter demyelination CSF + JC Virus Biopsy = Gold Standard PPx: Antiretroviral therapy Tx: There is no specific treatment for PML. The main strategy is restoring the host adaptive immune response which can prolong survival including starting/optimizing ARVs Cryptococcal Mengingitis (Caused by the fungus Cryptococcus neoformans) < 100 Symptoms of meningitis including headache, nausea/vomiting, fatigue, confusion, sensitivity to fever, stiff neck The cryptococcal antigen may be detected in CSF or blood. LP is diagnostic - elevated opening pressure, positive CSF crypt ag, CSF fungal culture Ppx: Not generally indicated Tx: Amphotericin B plus flucytosine followed by prolonged course of fluconazole Kaposi Sarcoma (Vascular tumor associated with human herpesvirus 8) < 200 Purple colored skin lesions (may occur on the mucosal surfaces where they can’t be visualized from the outside) Biopsy ART + Local or systemic therapy depending on the extent of the disease