Acute infection occurs 2 to 6 wk from the time of viral transmission.• It most often is a self-limited mononucleosis-like illness: pharyngitis, rash, splenomegaly, and lymphadenopathy, occasionally w/hepatitis and aseptic meningitis.
• The p24 antigen and the HIV PCR are detected; HIV serology first becomes (+) 1 mo later.
HIV viral Ab screening tests include:• Enzyme immuno assay (EIA): A (-) EIA excludes infection except during the acute phase following primary infection (window period) before seroconversion occurs. A (+) EIA is confirmed by western blot. Combination of (+) EIA and (+) western blot has 99.5% sensitivity and 99.9% specificity.
• Rapid serologic screening HIV antigen–coated gelatin or latex particle agglutination assays: They are less sensitive and specific than standard ELISA tests.
• Western blot confirmatory test: performed when EIA is (+). It identifies specific viral antigens.
• Tests are (+) when both core and envelope antigens are present.
• Indeterminate when either antigen is present: A false(+) result occurs if unchanged during 6 mo.
• An FDA-approved at-home HIV screening test is also available. It uses swabs of oral fluids from upper and lower gums. A positive test requires confirmatory testing in the office. Negative home tests should be repeated within 3 months.
Early stage (CD4 cells >400/mm3): Diffuse lymphadenopathy may be present. Levels of viral replication, 109 copies/day, occur at this stage even though the pt remains asymptomatic.
Middle stage (CD4 cells, 200-400/mm3)• Mycobacterium tuberculosis infections, recurrent herpes zoster, persistent mucocutaneous herpes simplex infections, and recurrent bacteremias caused by Streptococcus pneumoniae and Salmonella spp occur.
• Kaposi’s sarcoma, oral candidiasis, and hairy leukoplakia appear.
AIDS: advanced HIV infection (CD4 cell count <200/mm3). The classic opportunistic infections PCP, cerebral toxoplasmosis, cryptococcosis occur when CD4 cell count is <200/mm3; infections with CMV and MAC occur when CD4 cell count is <50/mm3.Management Strategies
Initial testing: CD4 cell count and HIV viral load (VL) are measured q3-6mo to guide decisions about antiretroviral use and prophylaxis against PCP and MAC infection.
Other testing: This identifies latent infections that may become reactivated because of loss of T-cell function but can be prevented by the use of specific agents.• Serology to Toxoplasma gondii (IgG): Clinical infection may be prevented by TMP-SMZ used as prophylaxis for PCP.
• VDRL test: LP should be performed in pts w/a confirmatory specific test (FTA). Rx w/IM benzathine PCN if the CSF formula is nl, and IV PCN × 10 days if the CSF VDRL test is reactive or CSF pleocytosis, protein, or hypoglycorrhachia is present.
• PPD skin test showing induration of ≥5 mm, or pts w/exposure to someone w/active TB: Treat w/INH 300 mg/day for 9 mo or, in case of INH-induced hepatitis, rifampin 600 mg PO qd (only for those not receiving PIs or NRTIs) × 4 mo.
Immunizations: Pts should receive the annual influenza vaccine each fall. Pneumococcal polysaccharide vaccine is recommended for all pts w/HIV infection and is most effective in those w/CD4 counts >200. Invasive pneumococcal infections occur w/↑ frequency in HIV-infected pts; these pts should be revaccinated every 5 yr. Hepatitis B vaccination is recommended for pts who have no evidence of prior infection. They should also receive hepatitis A vaccine.Prophylactic Agents
PJP prophylaxis if CD4 cell level is <200/mm3• TMP-SMZ (1 DS qd): most effective agent. It also provides protection against infections with T. gondii, Nocardia spp, and enteric pathogens.
• Adverse reactions to TMP-SMZ (GI distress, fever, rash, and leukopenia): occur in 40%. Discontinuation of drug may be necessary.
• Dapsone indicated w/TMP-SMZ rash; 30% w/TMP-SMZ toxicity develop reaction to dapsone.
• Aerosolized pentamidine, 300 mg/mo, and atovaquone, 750 mg bid, are third-line agents.
Prophylaxis against MAC in pts w/CD4 cell counts <50/µL Azithromycin 1200 mg weekly is the most effective agent.
Prophylaxis for several opportunistic infections can be discontinued if there has been a sustained CD4 cell count ↑ >200 associated w/ART (PCP, toxoplasmosis, cryptococcosis) and 100 for MAC for more than 3 to 6 mo.
Prophylaxis against toxoplasmosis if CD4 cell count <100/µL and positive serology: TMP-SMZ (IDS qd).
Prophylaxis against tuberculosis if TST>5 mm or +IGRA: INH, 300 mg/day × 9 months.Antiretroviral Therapy (ART)
Rx goals are maximal and durable suppression of VLs (<50 copies/mL), restoration of immunologic function (CD4 cell count), prevention of HIV disease progression, and prevention of transmission to an uninfected partner.
Agents in six separate drug classes are now available: NRTIs, NNRTIs, PIs, fusion inhibitors, co-receptor inhibitors, and integrase inhibitors.
The standard regimen is two NRTIs (TNF/3TC) plus an NNRTI (efavirenz [Sustiva] or rilpivirine), ritonavir-boosted PI agent (darunavir, lopinavir, atazanavir, fosamprenavir), or an integrase inhibitor (raltegravir, elvitegravir).
ART should be offered to all pts with HIV infection regardless of CD4 count and HIV VL. The rationale for early Rx is that the disorders associated with long-term viral replication—coronary artery disease, bone demineralization, renal disease, and possibly neurocognitive changes—may be averted or delayed if HIV VL is reduced with ART. ART at this stage may prevent transmission to an uninfected partner.
Indications for initiation of ART according to DHHS guidelines are: symptomatic HIV infection, CD4 cell count <500/µL, history of AIDS-defining opportunistic infection or malignancy, presence of HIV-associated nephropathy, active co-infection with hepatitis B or C virus, pregnancy (to prevent perinatal transmission).
After initiation of ART, measure CD4 counts and VLs at 1 and 4 mo. The criteria used to assess initial ART efficacy are as follows:• >1.0 log ↓ in HIV VL within 4 wk and undetectable VL (HIV RNA <50 copies/mL) within 4 mo
Pts should be evaluated q3mo at first to assess VL responses. In adherent pts with undetectable HIV VL, pts may be evaluated q6mo. A new regimen should be initiated in pts whose initial regimen has failed (rebound viremia).
CD4 counts on an average boost to 250 cells above baseline value within 1 to 2 yr of Rx; failure to achieve this boost in adherent pts with undetectable VL does not indicate ART failure and does not warrant changing the regimen.
Drug resistance testing should be performed when there is ART failure; a new regimen should be selected on the basis of antiviral hx and absence of mutations to ART-included agents on resistance testing. Once resistance develops to an agent in one class, cross-resistance to other drugs in the same class frequently occurs.
An ideal regimen should include preferably three agents from two separate drug classes to which the virus retains susceptibility. Agents frequently included in a new regimen include the following:• Raltegravir (400 mg bid) or elvitegravir: integrase inhibitors
• Maraviroc inhibits viral binding to co-receptor CCR5. A viral tropism assay must be first measured before initiation to ensure that the virus is an R5 strain.
• Etravirine (200 bid): an NNRTI to which certain NNRTI-resistant strains (K103N mutants) remain susceptible
• Darunavir/ritonavir (600/100 bid): a PI to which certain PI-resistant strains remain susceptible
NRTI agents and their toxicities• Zidovudine (Retrovir, AZT) 300 mg bid with lamivudine (Epivir, 3TC) 150 mg bid (Combivir). Transient myalgias, headache, and fatigue are common. Hematologic toxicity (leukopenia and anemia) is related to HIV disease status.
• Tenofovir (TNF, Viread) 300 mg/day in combination w/emtricitabine (FTC) 200 mg/day (Truvada). Nephrotoxicity is the major adverse reaction, w/declines in GFR of 8%.
• Abacavir (Ziagen) 300 mg bid; combined w/3TC (Epzicom, 1 tablet qd). Risk of abacavir hypersensitivity ↑ to 8% in pts w/HLA-B5701 genotype. Testing for the haplotype is indicated before starting abacavir.
• Zalcitabine (Hivid, ddC) 0.75 mg tid. It is rarely used because of relative lack of potency and tid schedule.
• Didanosine (Videx, ddI) 200 mg bid, or 400 mg enteric-coated tablet once qd. It is rarely used because of toxicities: pancreatitis (10%); peripheral neuropathy (15%).
NNRTI agents and their toxicities•
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