antiretroviral%20therapy%20for%20hiv-infected%20adults
ANTIRETROVIRAL THERAPY FOR HIV-INFECTED ADULTS
Antiretroviral therapy is recommended for all HIV-infected individuals regardless of CD4 count to decrease morbidity and mortality associated with HIV infection.
Goals of antiretroviral treatment are suppression of viral load for maximum possible duration, restore & preserve immunologic function, reduce HIV-related morbidity & mortality and prevent HIV transmission.
Urgent initiation of antiretroviral treatment is recommended in the following individuals: pregnant women, patients w/ HIV with coinfections (HBV, HCV, active tuberculosis), AIDS-defining illness, HIV-associated nephropathy, low CD4 counts, acute opportunistic infections and HIV HBV with evidence of chronic liver disease.

Assessment of Treatment Failure

  • Treatment failure can be defined as a suboptimal response to antiretroviral therapy
    • Often associated with virologic failure, immunologic failure, and/or clinical progression

Virologic Failure

  • Incomplete virologic response is when 2 consecutive plasma HIV RNA levels remain at >200 copies/mL after 24 weeks on ART regimen
  • Virologic rebound is confirmed detectable HIV RNA (>200 copies/mL) after virologic suppression
  • Persistent low-level viremia is confirmed detectable HIV RNA levels that are <1,000 copies/mL
  • Virologic blip is an isolated detectable HIV RNA level (after virologic suppression) that is followed by a return to virologic suppression
  • Virologic failure is the inability to achieve or maintain suppression of viral replication (to an HIV RNA level of <200 copies/mL)
    • Virologic suppression, on the other hand, is a confirmed HIV RNA level below the limit of assay detection (eg <48 copies/mL)
    • Caused by various factors (suboptimal adherence and drug intolerance/toxicity account for 28-40% of virologic failure)
      • Patient characteristics (eg comorbidities, prior AIDS diagnosis, lower pretreatment CD4 count, higher baseline HIV RNA level, prior treatment failure)
      • ART regimen characteristics (eg drug side effects and toxicities), drug interactions, suboptimal virologic potency and pharmacokinetics)
      • Healthcare provider characteristics (experience or expertise in HIV treatment)

Assessment of Virologic Failure

  • If virologic failure is suspected or confirmed, the following concerns should be addressed:
    • Occurrence of HIV-related clinical events
    • ARV treatment history
    • HIV RNA and CD4 T-cell count changes over time
    • Results of prior resistance testing
    • Medication-taking history (includes patient adherence, tolerability of medications, dosing frequency and pharmacokinetic issues)
    • Concomitant medications and comorbidities
  • Suspected drug resistance should be addressed by performing resistance testing while patient is on the failing ART regimen or within 4 weeks after discontinuation if the plasma HIV RNA level is >500 copies/mL
    • Drug resistance tests tend to be cumulative for a given patient; thus, all prior resistance test results and treatment history should be considered

Immunologic Failure

  • Despite virologic suppression on ART, CD4 cell count fails to show adequate response or persistently declines
  • Although no specific definition for immunologic failure exists, some studies have defined it as failure to increase CD4 counts above a specific threshold (eg >350 or 500 cells/mm3 over a period of 4-7 years)
    • CD4 counts in ART-naive patients with initial regimen increase to approx 150 cells/mm3 within the 1st year and a plateau may occur after 4-6 years of treatment with viral suppression
    • A persistently low CD4 count while on ART is associated with a small but appreciable risk of AIDS- and non-AIDS-related (eg cardiovascular, renal, hepatic diseases) morbidity and mortality

Assessment of Immunologic Failure

  • Confirm CD4 count by repeat testing
  • Assess comorbidities and untreated coinfections
  • Review medication history, focusing on those which are known to decrease WBC count, especially CD4 (eg interferon, Prednisone, cancer chemotherapy agents, Zidovudine, combination of TDF and Didanosine)

Clinical progression

  • Persistence or recurrence of HIV-related events (after at least 3 months on an antiretroviral regimen), excluding immune reconstitution syndromes or symptoms attributable to persistence of opportunistic infections that may require longer treatment

Follow Up

Patients on ART

  • Symptom-directed lab monitoring for safety and toxicity is recommended for those on ART
  • CD4 T-cell count and plasma HIV RNA (viral load) are the 2 markers used routinely to evaluate immune function and level of viremia
    • If resources are available, use viral load to confirm suspected treatment failure based on clinical and/or immunological criteria
  • Below are recommended laboratory parameters and monitoring schedule for patients after initiation of ART:
    • CD4 count: Every 3-6 months; in clinically stable patients with suppressed viral load, every 6-12 months
    • Viral load: 2-8 weeks post-ART initiation or modification
      • If HIV RNA is detectable at 2-8 weeks, repeat every 4-8 weeks until suppression to <200 copies/mL, then every 3-6 months
      • Every 3-4 months for patients on a stable ART regimen or as clinically indicated; may extend to every 6 months for adherent patients with suppressed viral load and stable clinical and immunologic status for >2-3 years
    • Fasting lipid profile: Consider every 4-8 weeks after initiating new ART then every 12 months if normal at last measurement and every 6 months if abnormal at last measurement
    • Fasting glucose: Consider every 3-6 months if abnormal at last measurement and every 6 months if normal at last measurement
    • CBC with differential count: 2-8 weeks post ART if on Zidovudine then every 3-6 months
    • Basic chemistry (serum Na, K, bicarbonate, chloride, BUN, creatinine), liver transaminases and total bilirubin: 2-8 weeks post-ART then every 3-6 months
      • Include phosphorus if on Tenofovir disoproxil fumarate (TDF) and Tenofovir alafenamide (TAF)
  • Urinalysis: Every 6 months if on TDF
    • More frequent monitoring may be indicated for patients with increased risk of renal insufficiency (eg DM, hypertensive patients)
  • In addition to viral load monitoring, other factors should be assessed such as adherence to prescribed ART regimen, altered pharmacology, drug interactions
  • Drug resistance testing for patients who fail to achieve viral suppression and aid in the choice of an alternative regimen

Patients Not Started on ART

  • Patients not yet eligible for ART should have CD4 count measurement every 6 months and more frequently as they approach the threshold to initiate ART
  • HBs Ag should be performed to help identify people with HIV/HBV coinfection so appropriate ART can be given (eg TDF-containing ART)
  • Patients should continue their regular visits for monitoring, prophylaxis and other medical treatment
  • ART should be discussed and offered again to patients who initially declined treatment
    • Discuss the benefits of ART and the risks of delaying the treatment
    • Provide support or counselling if lack of readiness, coping mechanisms or probable compliance difficulties are at issue

Post-Test Counselling

  • All individuals undergoing human immunodeficiency virus (HIV) testing should be counseled when their results are given, regardless of the test result

Human immunodeficiency virus (HIV)-positive patients

  • Clearly inform the patient of the test result and allow him/her the time to consider it
  • Ensure that the patient understands the result and allow questions to be asked
  • Provide emotional support and crisis management
  • Discuss any immediate concerns and determine available and acceptable social network to offer support
  • Discuss treatment and follow-up services available, including care and support services, prevention of mother-to-child transmission
  • Provide information on prevention of HIV transmission (including provision of male and female condoms and guidance on their use) and relevant health preventive measures (eg good nutrition)
  • Notification, counselling and referral for HIV testing of partners and children

Human immunodeficiency virus (HIV)-negative patients

  • Explanation of the test result, including information on the window period for the appearance of HIV antibodies and a recommendation to re-test in case of a recent exposure
  • Educate on methods of prevention of HIV transmission
  • Provision of male and female condoms and guidance on their use
  • Start ART to uninfected partner for prevention
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