antiretroviral%20therapy%20for%20hiv-infected%20adults
ANTIRETROVIRAL THERAPY FOR HIV-INFECTED ADULTS
Treatment Guideline Chart
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 and preserve immunologic function, reduce HIV-related morbidity and mortality and prevent HIV transmission.
Urgent initiation of antiretroviral treatment is recommended in the following individuals: Pregnant women, patients with 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.

Antiretroviral%20therapy%20for%20hiv-infected%20adults Diagnosis

Diagnosis

Initial Patient Visit

  • Human immunodeficiency virus (HIV) testing should be offered to all persons requesting HIV testing for any reason
  • HIV testing is recommended for all persons requesting evaluation for sexually transmitted infection and not known to have HIV infection
  • HIV screening/testing and counselling should be voluntary and undertaken only with the patient’s knowledge and understanding that HIV test is being planned
    • Persons at high risk for HIV should be screened for HIV at least yearly
    • The “5 Cs” must be observed - informed consent, counselling, confidentiality, correct test results and linkage to care
    • General informed consent for medical care should be enough to cover consent for HIV testing
    • If a patient declines an HIV test, this decision should be documented in the medical record
  • HIV screening should be part of the routine panel of prenatal screening tests for all pregnant women
    • Allows HIV-infected women and their infants to benefit from timely and appropriate interventions (ART medications, scheduled cesarean delivery, etc)
  • In all types of HIV epidemics, health care providers must recommend HIV testing and counselling as part of standard care to individuals who present to health facilities with signs, symptoms or medical conditions that indicate a probable HIV infection
  • In places with low-level and concentrated epidemics, HIV testing and counselling should not be recommended to all persons attending health facilities
    • In such settings, priority is to recommend HIV testing and counselling to all patients who present with signs and symptoms suggestive of an underlying HIV infection and to children who have been exposed perinatally to HIV
  • In generalized epidemics, HIV testing and counselling should be recommended to all individuals seen in all health facilities
    • HIV testing should be part of the normal standard of care provided to patients, regardless of the presence or absence of symptoms, or the reason for patient’s visit to the health facility
  • Regardless of type of epidemic setting, HIV testing and counselling are recommended to the following:
    • Patients of all age groups who present with signs and symptoms or medical conditions that could indicate HIV infection, including tuberculosis (TB)
    • HIV-exposed children or children born to HIV-positive women
    • Malnourished children in generalized epidemics who are not responding to appropriate nutritional therapy
    • Men who desire circumcision as an HIV prevention intervention

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
  • Reactive enzyme-linked immunosorbent assay (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

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 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 test and assure quality control

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

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 including immunization 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

Classification

Primary HIV Infection (PHI)

  • High-risk exposure within the previous 6 weeks, with virus detected in plasma (p24 Ag and/or HIV RNA) and/or with evolving anti-HIV antibody reactivity (negative or indeterminate to positive), with or without clinical symptoms

Classification of PHI

  • Acute HIV Infection: Detectable HIV RNA or p24 antigen in the setting of a negative or indeterminate HIV antibody test result
  • Recent HIV Infection: Detectable HIV antibody up to 6 months after infection

Staging

HIV Infection Stage Based on Western Blot or Immunoblot Patterns
Stage I

  • Positive HIV RNA only
  • Median viral load of 2,000 copies/mL and approximately 10% of people living with HIV have <100 copies/mL

Stage II

  • Positive HIV RNA and p24 Ag only
  • HIV RNA >10,000 copies/mL

Stage III

  • Positive HIV RNA, p24 Ag and anti-HIV antibody by immune assay, without specific Western Blot bands

Stage IV

  • Positive HIV RNA, p24 Ag and anti-HIV antibody by immune assay, with indeterminate Western Blot pattern

Stage V

  • Positive HIV RNA, p24 Ag and anti-HIV antibody by immune assay, with reactive Western Blot pattern but lacking p31 reactivity

Stage VI

  • Positive HIV RNA, p24 Ag and anti-HIV antibody by immune assay, with full Western Blot reactivity including p31 band

Clinical Staging of 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 (PML), 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 septicemia (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
    • Pharyngitis
    • 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)

  • Assess level of HIV viremia
  • 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 antiretroviral (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 copies/mL), depending on the assay used
  • Viral suppression is generally achieved in 8-12 weeks after ART initiation or modification due to virologic failure, 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

CD4 T-cell Count

  • Serves as a major indicator of immune function
  • One of the key factors in deciding the urgency to start ART and the need to initiate prophylaxis for opportunistic infections before ART initiation
  • Strongest predictor of subsequent disease progression and survival
  • Used to assess immunologic response after ART initiation and the need for discontinuing prophylaxis for opportunistic infections
  • 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 in the 1st year of ART with an accelerated response in the 1st 3 months of therapy 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

HIV Drug Resistance Testing

  • Should be done upon entry into care, regardless of whether ART will be started immediately or deferred and during ART initiation and modification
    • 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 (VL) level and CD4 count must be obtained to have a baseline in assessing the patient's subsequent response
      • Standard genotypic drug resistance testing for reverse transcriptase and protease gene mutations are recommended and testing for integrase gene mutations is performed if resistance to transmitted integrase strand transfer inhibitor (INSTI) is suspected in newly diagnosed HIV or in patients who acquired HIV after receiving long-acting Cabotegravir (CAB-LA) as pre-exposure prophylaxis
    • Viral amplification for drug resistance testing is recommended in patients with HIV RNA levels <1,000 copies/mL

HLA-B*5701 Screening

  • Recommended prior to initiating Abacavir-containing regimen to reduce the risk of hypersensitivity reaction

Coreceptor Tropism Assays

  • Used during ART initiation and modification whenever a CCR5 inhibitor (eg Maraviroc) is being considered
  • Also considered if patients exhibit virologic failure on Maraviroc or any CCR5 inhibitor
  • Phenotypic tropism assay is preferred to determine HIV-1 coreceptor usage
    • European guidelines also recommend performing genotypic tropism assay in the determination of coreceptor usage in patients with HIV RNA >1,000 copies/mL and preferably in patients with HIV RNA ≤1,000 copies/mL

Blood Tests

  • Complete blood count (CBC), transaminase levels, blood urea nitrogen (BUN), creatinine, serum electrolytes (eg Na, K, Cl, HCO3) should be performed upon entry into care and during ART initiation and modification
  • Fasting blood sugar is performed upon entry into care and during ART initiation or modification and lipid levels is determined upon entry into care

Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Infection Screening

  • Recommended before ART initiation and periodically after ART initiation if indicated, because treatment of these coinfections may affect the choice of ART and the likelihood of drug-induced hepatotoxicity

Urinalysis

  • Performed upon entry into care

Other Tests

  • Include tests for cancer, sexually transmitted infections and tests for determining risk of opportunistic infections
  • Pregnancy test: If patient will be started on Efavirenz
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