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.

Diagnosis

Pretest Counseling and Informed Consent

  • Risk assessment and education focused on prevention should be done prior to and after receiving test results
  • The following information should be provided by health care providers when recommending human immunodeficiency virus (HIV) testing and counseling:
    • Reasons why HIV testing and counseling is being offered and their benefits and potential risks (eg discrimination, abandonment)
    • Services that are available, including ART, in either an HIV-positive or an HIV-negative test result
    • That the patient has a right to decline the test and that result will be treated with confidentiality; patient’s decision to decline should be noted in the medical record
    • In critically ill or unconscious patients where informed consent is not possible, permission should be sought from the patient’s next-of-kin, guardian or other caregiver; in the absence of such person, the health care provider should act according to the best interest of the patient
    • In case of an HIV-positive test result, disclosure to other persons who may be at risk of exposure to HIV should be encouraged
    • An opportunity for the patient to ask the health care provider questions

Screening

Human Immunodeficiency Virus (HIV) Test

  • Choice of HIV test depends on various factors such as cost and availability of equipments or test kits, laboratory expertise, availability of staff, number of samples to be tested, collection and transport of samples, convenience, setting where testing will be performed, ability of the patients to come back for the results
  • Testing strategies are either done as:
    • Parallel testing: Recommended when using whole blood as samples; 2 tests are simultaneously done using assays based on different antigens; concordantly negative or positive results are reported as true negatives or positives, respectively
    • Serial testing: If the HIV antibody test is negative, it is reported as “negative”; if test result is positive, the specimen undergoes a second test using an antigen different from the first; a second positive result is considered a true positive
      • In low-prevalence setting where false positive results are likely, a third confirmatory test may be done
      • Recommended due to its cheaper cost; a second test is only required for reactive initial test results
  • Rapid HIV tests
    • Eg OraQuick Rapid HIV-1/2 Antibody Test, Reveal G3 Rapid HIV-1 Antibody Test, Uni-Gold Recombigen HIV Test, Clearview HIV 1/2 Stat Pack, Clearview Complete HIV 1/2, Multispot HIV-1/HIV-2 Rapid Test
    • May either be done as serial or parallel testing
    • Provide accurate results within a much shorter time compared with traditional enzyme-linked immunosorbent assays (ELISA)
    • Advantages include visibility of the test and quick turn-around, testing can occur outside lab settings, does not require specialized equipment; however, trained lab supervisors are required to supervise and assure quality control
  • Enzyme-linked immunosorbent assay (ELISA)
    • Are almost always serial in nature
    • Preferred method when large numbers of tests need to be performed (allows large numbers of samples to be tested efficiently at one time)
    • Disadvantages include longer time to assemble enough samples to make a test run, longer reporting time of the results (half day), precluding outpatients receiving the test result at the same visit, requires certified lab staff to manage the test procedure, report results and maintain equipment
  • Reactive ELISA or rapid test must be followed by a Western blot
  • Negative ELISA or rapid test or a reactive ELISA or rapid test with negative or indeterminate Western blot should be followed by a virologic test (ie p24 antigen or HIV RNA assay); a positive virologic test in this case, is consistent with acute HIV infection
  • If an acute HIV infection is diagnosed by a positive virologic test and preceded by a negative HIV antibody test, a confirmatory HIV antibody test should be performed over the next 3 months to confirm seroconversion

Evaluation

  • Goals of initial evaluation include confirmation of the presence of human immunodeficiency virus (HIV) infection, gathering of appropriate baseline historical and laboratory information, ensuring patient understanding of HIV infection and its transmission, and initiation of care as recommended by established guidelines
  • Initial evaluation consists of complete medical history, physical examination and laboratory evaluation
  • Evaluation must also include assessment of social support, comorbidities, substance abuse, high-risk behaviors, mental illness, economic factors
  • Patient should be counseled regarding the implications of HIV infection

Staging

Clinical Staging of Human Immunodeficiency Virus (HIV) Disease in Adults and Adolescents

  • HIV disease staging and classification systems are critical tools for providing clinicians and patients with important information about HIV disease stage and clinical management. Two major classification systems currently are in use: The U.S. Centers for Disease Control and Prevention (CDC) classification system and the World Health Organization (WHO) Clinical Staging and Disease Classification System
  • Assessment used where HIV infection has been confirmed by HIV antibody testing and serves to guide decisions on when to initiate ART
  • Clinical stage 1: Asymptomatic, persistent generalized lymphadenopathy
  • Clinical stage 2: Unexplained moderate weight loss (approximately <10% of estimated or actual body weight), recurrent oral sores, angular cheilitis, pruritic papular lesions, seborrheic dermatitis, recurrent respiratory tract infections (eg tonsillitis, pharyngitis, otitis media, sinusitis), fungal nail infections, herpes zoster
  • Clinical stage 3: Unexplained severe weight loss (>10% of estimated or measured body weight), unexplained persistent fever (intermittent or constant) lasting for >1 month, unexplained diarrhea lasting for >1 month, unexplained neutropenia (< 0.5 x 109/L), anemia (<8 g/dL), and/or chronic thrombocytopenia (<50 x 109/L), oral hairy leukoplakia, persistent oral candidiasis, acute necrotizing stomatitis, gingivitis or periodontitis, pulmonary tuberculosis, severe bacterial infection (eg pneumonia, empyema, meningitis, pyomyositis, bone and joint infection, bacteremia, severe pelvic inflammatory disease)
  • Clinical stage 4: HIV wasting syndrome, recurrent bacterial pneumonia, extrapulmonary tuberculosis, cytomegalovirus disease, Kaposi’s sarcoma, disseminated mycosis, recurrent septicemia, disseminated nontuberculous mycobacterial infection, lymphoma, progressive multifocal leukoencephalopathy, HIV encephalopathy, Pneumocytis jirovecii, chronic herpes simplex (urolabial, genital, anorectal of >1mm or visceral at any site), esophageal candidiasis (trachea, bronchi and lungs), CNS toxoplasmosis, extrapulmonary cryptococcosis, including meningitis, chronic cryptosporidiosis, chronic isosporiasis, disseminated mycosis (histoplasmosis, coccidiomycosis) recurrent septicaemia (including nontyphoidal Salmonella), lymphoma (cerebral or B cell non-Hodgkin), invasive cervical carcinoma, atypical disseminated leishmaniasis and symptomatic HIV-associated nephropathy or HIV-associated cardiomyopathy

History

  • Signs, symptoms and laboratory findings of acute human immunodeficiency virus (HIV) infection with recent (within 2-6 weeks) high risk of exposure to HIV may include (but are not limited to):
    • Fever
    • Skin rash
    • Headache
    • Diarrhea
    • Myalgia, arthralgia
    • Lymphadenopathy
    • Oral ulcers
    • Leucopenia, thrombocytopenia
    • Elevated transaminase level
  • High-risk exposures include sexual contact with an HIV-infected person or with an individual at risk for HIV, sharing of injection drug use paraphernalia, contact with potentially infectious blood with mucous membranes or breaks in the skin

Laboratory Tests

  • Human immunodeficiency virus (HIV) Antibody Testing
    • Done if no prior documentation is available or if HIV RNA is below the assay’s limit for detection
  • Plasma HIV RNA (viral load)
    • Most important indicator of initial or sustained response to antiretroviral therapy (ART)
      • Should be measured in all HIV-infected patients upon start of care and therapy then on a regular basis thereafter
    • Pre-treatment viral load level is taken into consideration in selecting initial ARV regimen
      • Due to poorer responses in patients with high baseline viral load
    • Optimal viral suppression is generally defined as a viral load persistently below the level of detection (<20-75 copies/mL), depending on the assay used
    • Viral suppression is generally achieved in 12-24 weeks, provided patient is adherent to their ART regimen and does not develop resistance to the prescribed drugs
    • Early detection of virological failure allows better preservation of the efficacy of second-line regimens
    • In settings where resources are limited, measurement of plasma viral load is not required prior to initiation of ART
    • Measurement is done:
      • After initiation of therapy because of virologic failure within 2-4 weeks but not later than 8 weeks after treatment initiation or modification
      • Repeat viral load measurement at 4-8 weeks interval until the level falls below the assay’s limit of detection
      • In virologically suppressed patients in whom ART was modified because of drug toxicity or for regimen simplification, measurement should be performed within 4-8 weeks after changing the therapy
      • Viral load test is repeated every 3-4 months or as clinically indicated in patients who are on stable and suppressive ARV regimen. It may be extended up to 6 months if the viral load was suppressed for >2 years and if the clinical and immunologic status are stable
      • Frequency of monitoring in patients within suboptimal response to ART will depend on the adherence and availability of other treatment options
  • CD4 T-cell count
    • Serves as a major indicator of immune function
    • One of the key factors in deciding whether to start ART and prophylaxis for opportunistic infections
    • Strongest predictor of subsequent disease progression and survival
    • An adequate CD4 response for most patients on ART is defined as an increase in CD4 count in the range of 50-150 cells/mm3 per year except in patients within a low starting CD4 count and in those with an advanced age who may show a blunted increase despite virologic suppression
    • Should be monitored every 3-4 months to determine when to initiate ART in untreated patients, evaluate immunologic response to ART and to determine the need for initiation or discontinuation of prophylaxis for opportunistic infections
    • In patients with consistently suppressed viral loads, CD4 count may be monitored every 6-12 months, unless there are changes in the clinical status of the patient
    • 3-6 months intervals was recommended in patients who fail to maintain viral suppression on ART and those who were already on ART for 2 years
  • CBC, transaminase levels, BUN, creatinine, hepatitis A, B and C serologies, urinalysis
  • Fasting blood sugar and lipid levels
  • HIV drug resistance testing should be done upon entry into care, regardless of whether ART will be started immediately or deferred
    • Genotypic testing is the preferred resistance testing to guide the selection of initial regimen in ART-naive patients
      • It is recommended that prior to starting ART, a repeat HIV viral load level & CD4 count must be obtained to have a baseline in assessing the patient's subsequent response
    • Helps in the selection of alternative regimens in patients who fail to achieve viral suppression
    • Is also performed when managing suboptimal viral load reduction
    • Should be done while the patient is taking ART regimen or within 4 weeks of treatment discontinuation
  • HLA-B*5701 screening
    • Recommended prior to initiating Abacavir-containing regimen to reduce the risk of hypersensitivity reaction
  • Pregnancy test: If patient will be started on Efavirenz
  • Coreceptor tropism assays are used whenever a CCR5 inhibitor (eg Maraviroc) is being considered
    • Also considered if patients exhibit virologic failure on Maraviroc or any CCR5 inhibitor
  • Other tests include tests for sexually transmitted infections and tests for determining risk of opportunistic infections
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