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
Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Infectious Diseases - Malaysia digital copy today!
DOWNLOAD
Editor's Recommendations
Most Read Articles
30 Nov 2017
Fluarex Tetra - Inactivated quadrivalent influenza vaccine (split virion) vaccine (inj) 0.5 mL - GlaxoSmithKline
02 Nov 2017
In this issue of MIMS Anti-Infective Supplement, we bring you clinical updates related to combating infectious diseases, and also a symposium highlight in conjunction with the launch of ceftolozane/tazobactam (Zerbaxa; Merck Sharp & Dohme Sdn Bhd) in Malaysia. 
Stephen Padilla, 20 Nov 2017
Diclofenac reduces the use of antibiotics in women with uncomplicated lower urinary tract infection (UTI) but remains less effective than norfloxacin for symptom relief of UTI, according to a recent study. In addition, diclofenac appears to be associated with an elevated risk of pyelonephritis.