Contents
Overview
Initial Patient Visit
Evaluation
Indications & Recommendations for Starting Antiretroviral Therapy (ART)
Follow-Up
Assessment of Treatment Failure
Test For HIV
HIV Test
Antiretroviral Therapy
Management of Patients w/ Treatment Failure
Guideline References
OVERVIEW
- Antiretroviral therapy (ART) is recommended for all human immunodeficiency virus (HIV)-infected individuals regardless of CD4 count to decrease morbidity & mortality associated w/ 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 human immunodeficiency virus (HIV) transmission
- Urgent initiation of antiretroviral treatment is recommended in the following individuals: pregnant women, patients HIV w/ coinfections (HBV, HCV, active tuberculosis), AIDS-defining illness, HIV-associated nephropathy low CD4 counts, acute opportunistic infections and HIV HBV w/ evidence of chronic liver disease.
Initial Patient Visit
- HIV testing should be offered to all persons requesting HIV testing for any reason
- HIV screening/testing & counselling should be voluntary & undertaken only w/ the patient’s knowledge & 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 & 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 & their infants to benefit from timely & appropriate interventions (ART medications, scheduled cesarean delivery, etc)
- In all types of HIV epidemics, health care providers must recommend HIV testing & counselling as part of standard care to individuals who present to health facilities w/ signs, symptoms or medical conditions that indicate a probable HIV infection
- Types of HIV epidemics:
- Low-level epidemic is when HIV may have existed for many years but has never spread to significant levels in any sub-population; recorded infection is largely confined to high-risk individuals [eg drug injectors, sex workers, men having sex w/ other men (MSM)]; HIV prevalence has not consistently exceeded 5% in any sub-population
- Concentrated HIV epidemics is when HIV has spread rapidly in a defined sub-population but is not well established in the general population; HIV prevalence is consistently >5% in at least one sub-population but is <1% in pregnant women in urban areas
- Generalized HIV epidemic is when HIV is firmly established in the general population; HIV prevalence is consistently >1% in pregnant women
- In places w/ low-level & concentrated epidemics, HIV testing & counselling should not be recommended to all persons attending health facilities
- In such settings, priority is to recommend HIV testing & counselling to all patients who present w/ signs & symptoms suggestive of an underlying HIV infection & to children who have been exposed perinatally to HIV
- In generalized epidemics, HIV testing & 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 & counselling are recommended to the following:
- Patients of all age groups who present w/ signs & 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
Refer to Symptoms for information regarding HIV testing
Top
Evaluation
- Goals of initial evaluation include confirmation of the presence of HIV infection, gathering of appropriate baseline historical & laboratory information, ensuring patient understanding of HIV infection & its transmission, & initiation of care as recommended by established guidelines
- Initial evaluation consists of complete medical history, physical examination & lab 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
Refer to Symptoms for more information on evaluation
Top
Indications & Recommendations for Starting Antiretroviral Therapy (ART)
- Regardless of CD4 cell count or WHO clinical stage, initiation of ART is strongly recommended for individuals w/ the following conditions:
- All pregnant & breastfeeding women w/ acute or recent HIV infection should start a combination ART as soon as possible to prevent mother-to-child transmission of HIV
- History of an AIDS-defining illness
- HIV-associated nephropathy
- HIV/hepatitis B virus (HBV) & HIV/Hepatitis C (HCV) coinfections
- HIV/Active tuberculosis disease coinfection
- TB treatment should also be started immediately
- Advanced HIV disease (clinical stage 3 or 4)
- HIV-positive partners in serodiscordant couples
- Treat all patients including asymptomatic individuals w/ CD4 T-cell count of 350-500 cells/mm3 regardless of the clinical stage but prioritize patients w/ CD4 cell count of <350 cells/mm3 & those w/ advanced HIV disease
- ART should be offered to patients who are at risk of transmitting HIV to sexual partners
- Effective ART has been shown to prevent transmission of HIV from an infected individual to a sexual partner
- ART is recommended in patients >50 years of age, regardless of CD4 cell count
- Immunologic response to ART may be reduced & risk of non-AIDS complications may increase in older HIV-infected patients
- ART is recommended for all HIV-infected individuals to reduce the risk of disease progression & prevent its transmission
- Patients starting ART should be willing, able to commit, understand the risks & benefits of therapy & the importance of adherence
Top
Goals of Antiretroviral Treatment
- Suppression of viral load for maximum possible duration
- Restore & preserve immunologic function
- Reduce HIV-related morbidity & mortality
- Improve quality of life
- Prevent HIV transmission
Refer to Treatment for more information regarding Antiretroviral Therapy
Follow-Up
Patients on ART
- Symptom-directed lab monitoring for safety & toxicity is recommended for those on ART
- CD4 T-cell count & plasma HIV RNA (viral load) are the 2 markers used routinely to evaluate immune function & level of viremia
- If resources are available, use viral load to confirm suspected treatment failure based on clinical &/or immunological criteria
- Below are recommended laboratory parameters & monitoring schedule for patients after initiation of ART:
- CD4 count: Every 3-6 months; in clinically stable patients w/ 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 parents w/ suppressed viral load & stable clinical & 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 & every 6 months if abnormal at last measurement
- CBC w/ 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 & total bilirubin: 2-8 weeks post-ART then every 3-6 months
- Include phosphorus if on Tenofovir disoproxil fumarate (TDF)
- Urinalysis: Every 6 months if on TDF
- More frequent monitoring may be indicated for patients w/ 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 & 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 & more frequently as they approach the threshold to initiate ART
- HBs Ag should be performed to help identify people w/ HIV/HBV coinfection so appropriate ART can be given (ie TDF-containing ART)
- Patients should continue their regular visits for monitoring, prophylaxis & other medical treatment
- ART should be discussed & offered again to patients who initially declined treatment
- Discuss the benefits of ART & the risks of delaying the treatment
- Provide support or counselling if lack of readiness, coping mechanisms or probable compliance difficulties are at issue
Top
Assessment of Treatment Failure
- Treatment failure can be defined as a suboptimal response to antiretroviral therapy. It is often associated with virologic failure, immunologic failure, &/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 (ie <48 copies/mL)
- Caused by various factors (suboptimal adherence & 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 & toxicities), drug interactions, suboptimal virologic potency & pharmacokinetics)
- Health care 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 & CD4 T-cell count changes over time
- Results of prior resistance testing
- Medication-taking history (includes patient adherence, tolerability of medications, dosing frequency & pharmacokinetic issues)
- Concomitant medications & comorbidities
- Suspected drug resistance should be addressed by performing resistance testing while patient is on the failing ART regimen or w/in 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 & 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 w/ initial regimen increase to approx 150 cells/mm3 w/in the 1st year & a plateau may occur after 4-6 years of treatment w/ viral suppression
- A persistently low CD4 count while on ART is associated w/ a small but appreciable risk of AIDS- & non-AIDS-related (eg cardiovascular, renal, hepatic diseases) morbidity & mortality
Assessment of Immunologic Failure
- Confirm CD4 count by repeat testing
- Assess comorbidities & 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 & 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
Below is an overview of disease management of HIV:
Top
Version: 3 August 2015
Guideline References:
- Coffey S. Antiretroviral therapy. AETC National Resource Center. http://www.aidsetc.org/aidsetc?page=cg-401_antiretroviral_therapy. Jun 2012. Accessed 26 Sep 2012
- Department of Health and Human Services Centers for Disease Control and Prevention. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR. 2006 Sep;55:1-17. Accessed 18 Sep 2012. PMID: 16988643
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1- selected adults and adolescents. Department of Health and Human Services. AIDSinfo. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Accessed 2 Jun 2015.
- Williams I, Churchill D, Anderson J, et al. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012. HIV Medicine. 2012 Sep;13:1-85. doi: 10.1111/j.1468-1293.2012.01029_1.x. Accessed 17 Sep 2012. PMID: 22830364
- World Health Organization, UNAIDS. Guidance on provider- initiated HIV testing and counselling in health facilities. WHO. http://whqlibdoc.who.int/publications/2007/9789241595568_eng.pdf. 2007
- World Health Organization. Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach: 2010 revision. WHO. http://whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf. 2010. Accessed 2 Jun 2015.
- World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: summary of key features and recommendations. WHO. http://www.who.int/hiv/pub/guidelines/arv2013/short_summary/en/index.html. Jun 2013. Accessed 01 Oct 2013
- World Health Organization. HIV/AIDS Fact sheet N°360. WHO. http://www.who.int/mediacentre/factsheets/fs360/en/. 2015. Accessed 2 Jun 2015.
- World Health Organization. WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. WHO. http://www.who.int/hiv/pub/guidelines/HIVstaging150307.pdf. 2007. Accessed 24 Sep 2012