More than 35 years after the medical community first recognized acquired immunodeficiency syndrome (AIDS), the disease, and the human immunodeficiency virus (HIV), that causes it remain a serious global health challenge. HIV attacks the body’s immune system by destroying T cells and leaving the person susceptible to opportunistic infections or infection-related cancers, which signal that the patient has AIDS, the last stage of HIV infection.1
The most common mode of infection is through sexual contact, followed by blood-borne and mother-to-child transmission.2
Worldwide, 36.7 million people currently live with HIV/AIDS, but as of June 2016, only 18.2 million of those were regularly accessing antiretroviral therapy, the primary treatment for the still-incurable disease.3
These guidelines provide an overview of the current recommendations surrounding HIV/AIDS diagnosis, treatment, and complications.
HIV testing and counseling is an essential first step in controlling the virus, but the World Health Organization (WHO) reports that only about half of people currently infected with HIV worldwide are aware of their status.4
This proportion is even lower among people in key at-risk populations, including men who have sex with men, people who inject drugs, people in prisons, sex workers, and transgender people. People in these groups tend to test late or have insufficient links from testing to care, meaning that their immune systems are already compromised when treatment is initiated.
The WHO guidelines emphasize some important components of successful HIV testing.4
First, counseling must be provided both before and after testing to provide accurate information about the potential test results, allowing the person to make informed choices. Even for people who test negative, counselors can offer helpful advice on safer sex and risk reduction.
Thanks to the advances in rapid HIV testing, screening can and should occur across multiple settings, including within community outreach efforts, healthcare provider offices, and clinics. Another development that could increase access is the availability of self-testing, which can be performed at home and requires physician follow-up in the event of a positive result. The test can be done at home in less than 20 minutes using either oral fluid or blood from a finger prick. In a statement announcing newly issued guidelines on self-testing, WHO Director Dr Margaret Chan said that self-testing “should open the door for many more people to know their HIV status and find out how to get treatment and access prevention services.”5
Self-testing could potentially be a key tool in helping to ensure confidentiality, one of the WHO’s essential "5 Cs" of HIV testing. The others are consent, counseling, correct test results, and connections to treatment. Counseling and confidentiality are especially important for adolescents, who should be able to obtain testing without parental knowledge and should be supported in their decision on whether to disclose positive HIV status.4
The CDC guidelines on laboratory testing for the diagnosis of HIV were updated in 2014 after years of literature review. To summarize the new algorithm, testing of serum or plasma should begin “with a combination immunoassay that detects HIV-1 and HIV-1 antibodies and HIV-1 p24 antigen. All specimens reactive on this initial assay undergo supplemental testing with an immunoassay that differentiates HIV-1 from HIV-2 antibodies. Specimens that are reactive on the initial immunoassay and nonreactive or indeterminate on the antibody differentiation assay proceed to HIV-1 nucleic acid testing for resolution.”6
If a positive test result occurs after this recommended algorithm, the patient will then undergo further testing, including HIV-1 viral load, CD4+ T-lymphocyte determination, and an antiretroviral resistance assay, to determine the stage of the disease and help select an appropriate treatment regimen.
This represents a change from the previous guidelines, which recommended using the HIV-1 Western blot and HIV-1 indirect immunofluorescence assay (IFA). In the interim before the release of the updated guidelines, the FDA had approved various improved immunoassay tests, including one that can differentiate HIV-1 from HIV-2 antibodies. The updates are based on these advances, as well as on evidence that Western blot and IFA tests “can produce false-negative or indeterminate results early in the course of HIV infection,” and that the Western blot often misclassifies HIV-2 infections as HIV-1.6
Aside from the improved accuracy, the new testing algorithm can also help shorten the interval between specimen collection and test result notification by 1 week, according to a testing program cited in the guidelines. Another laboratory found that 96% of antibody-positive results could be reported in 2 workdays or less when using the new algorithm, compared with 22% for the specimens tested with the previous algorithm.6
The guidelines also included recommendations for reporting test results to both the person who ordered the test and public health authorities. They advise that reports to the person who ordered the test should specify all assays used and their results, how to interpret the results, and any additional tests that may be required. All results should be reported to the person when testing is complete, but laboratories should only report results indicative of HIV infection to the appropriate public health authorities. Tests indicating the presence of acute HIV infection call for expedited reporting to both the infected person and to public health authorities.6
The primary treatment for HIV is antiretroviral therapy (ART), which has been shown to improve survival rates and immune system function, decrease the risk of complications, and reduce the likelihood of HIV transmission.7
Therapy typically consists of a regimen of 3 or more antiretroviral (ARV) drugs. In the US, there are over 20 individual ARVs in 6 classes, which can be combined in a regimen tailored to each individual patient.7,8
The formulation of these regimens will depend on the patient’s comorbidities and disease stage, potential side effects, and possible interactions with the patient’s concomitant medications.8
ART works by inhibiting HIV replication so as to lower the viral load of HIV RNA in plasma, which then “delays or prevents the selection of drug-resistance mutations, preserves or improves CD4 T lymphocyte (CD4) cell numbers, and confers substantial clinical benefits.”8
Effective ART can also reduce the risk of HIV transmission to sexual partners by more than 96% by lowering the viral load. Complete eradication of HIV infection cannot be achieved with ART, so therapy must be continued to achieve viral suppression. Viral suppression below assay detection limits generally occurs within the first 12 to 24 weeks of therapy. Predictors of success include low baseline viral load, high potency of the ARV regimen, and stringent patient adherence, which is more likely if the regimen is both tolerable and convenient.
Several guidelines agree that ART should be initiated in all people with HIV, but there are some conditions that increase the urgency of treatment initiation:
Note: 1 cubic millimeter (mm3) = 1 microliter (µL) = 0.001 milliliter
AIDS-defining conditions, including HIV-associated dementia and AIDS-associated malignancies7,8
Acute opportunistic infections7,8
Lower CD4 counts (<200 cells/mm3 [7,8]; <350 cells/mm3 )
Severe or advanced HIV clinical disease (WHO stage 3 or 41)9
HIV/hepatitis B virus coinfection7,8
HIV/hepatitis C virus coinfection7,8
Rapidly declining CD4 counts (eg, >100 cells/µL/year)7
Higher viral loads (eg, >100,000 copies/mL)7
Experts unanimously agree that patient adherence to the ART regimen is essential to achieving viral suppression and, therefore, better clinical outcomes and survival. Adherence is second only to CD4 cell count as a predictor of HIV progression to AIDS and death.7
Average ART adherence in the United States is about 70%.7
Because adherence is so central to therapy success, numerous guidelines offer suggestions on how to develop individual support plans for each patient during every stage of the care continuum.
Before treatment: establish trusting relationship with patient7; ensure patient readiness to begin treatment7,8; identify potential barriers to successful medication adherence7,8; provide mental health and substance abuse resources if necessary7,9
Regimen selection: involve patient in selection of regimen7,8; tailor regimen to patient’s circumstances8; consider a fixed-dose combination or a once-daily regimen9
Access: provide resources to obtain prescription drug coverage7; use patient prescription assistance programs8
Adherence tools: reminder devices8,9; pill boxes7,8; visual aids like planners and calendars7; text messaging9
Community resources: peer counselors8,9; visiting nurses, community workers, family members, treatment navigators8; adherence clubs9
Behavioral interventions: positive reinforcement of successes7,8; motivational interviewing8; behavioral skills training9; health literacy support7
Assessment: assess adherence at every clinic visit7,8; identify reasons for nonadherence7; follow up on missed visits8; confirm adherence via pharmacy refill records, pill counts, and viral load monitoring9
The CDC has also compiled a list of specific interventions that have strong evidence supporting their efficacy. These include programs that administer ART in methadone clinics, interventions to help serodiscordant couples (1 HIV-positive and 1 HIV-negative partner) manage adherence together, and text messaging reminders for young adults.10
Due to their reduced immune system function, individuals with HIV are more susceptible to opportunistic infections (OIs), which are the leading cause of morbidity and mortality among this population.11
According to the National Institutes of Health guidelines on OIs, “the widespread use of potent ART has had the most profound influence on reducing OI-related mortality in HIV-infected persons.”11
These and other guidelines identify several strategies for OI prevention, including immunizations, OI prophylaxis, and exposure avoidance.
The following vaccinations are recommended to reduce the risk of preventable infections in all individuals with HIV: influenza; tetanus/diphtheria/pertussis; human papillomavirus (female or male); pneumococcal polysaccharide; pneumococcal 13-valent conjugate; and hepatitis B. The meningococcal and hepatitis A vaccines are recommended when certain risk factors are present, such as living in a dormitory for meningococcal or chronic liver disease for hepatitis A. Live vaccines (varicella, zoster, measles/mumps/rubella) are contraindicated for use in patients with severe immunosuppression, defined as a CD4 count of <200 cells/µL.7,11
Prophylaxis is used to prevent either a first episode or a recurrence of an OI. Guidelines recommend the initiation of prophylaxis against 3 main OIs when CD4 count falls below a certain threshold: Pneumocystis
pneumonia (<200 cells/µL), Toxoplasma gondii
encephalitis (<100 cells/µL), and Mycobacterium avium complex disease (<50 cells/µL).7,11
Several other recommendations are in place for the indication of prophylaxis depending on the presence of various risk factors. For instance, patients with latent Mycobacterium tuberculosis
infection should receive prophylaxis to prevent tuberculosis. Prophylaxis is encouraged in endemic regions for Histoplasma capsulatum,
coccidioidomycosis, malaria, and penicilliosis.
In the course of daily life, patients will inevitably encounter potential sources of infection, but the risk of contracting an illness can at least partially be mitigated through careful exposure prevention. Each of the exposure types listed below is followed by some of the pertinent risk reduction strategies for HIV patients.7,11
Sexual exposures: using condoms, frequent testing for sexually transmitted diseases, avoiding risky sexual practices
Injection-drug-use exposures: substance abuse counseling and treatment, safer injection practices like one-time use of equipment, syringe-exchange programs, sterile preparation of drugs, safe disposal
Environmental and occupational exposures: frequent handwashing for parents or childcare providers, gloves and hand hygiene for contact with animals, avoiding contact with young farm animals or soil
Pet-related exposures: avoiding stray animals, wearing gloves or not handling animal feces, not allowing animals to lick patient’s open cuts, avoiding cleaning cat litter boxes whenever possible, avoiding contacts with reptiles and exotic pets
Food- and water-related exposures: safe food preparation including thorough cooking of meat, washing produce, avoiding food cross-contamination, avoiding potentially contaminated water sources
Travel-related exposures: researching risks in intended destinations, avoiding potentially contaminated food and tap water, special attention to good hygiene, receiving any indicated vaccines
Bloodborne exposures: following infection control procedures for tattoos or piercings, receiving CMV antibody-negative or leukocyte-reduced blood transfusions
Respiratory and bodily exposures: avoid people with tuberculosis, chickenpox, shingles, etc.
1. Centers for Disease Control and Prevention. About HIV/AIDS. CDC website. http://www.cdc.gov/hiv/basics/whatishiv.html
. Published November 30, 2016. Accessed December 7, 2016.
2. Rom WN, Markowitz SB. Environmental and Occupational Medicine.
4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007.
3. UN AIDS. Fact sheet November 2016. UN AIDS website. http://www.unaids.org/en/resources/fact-sheet
. Published November 2016. Accessed December 7, 2016.
4. World Health Organization. Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations – 2016 update. WHO website. http://apps.who.int/iris/bitstream/10665/246200/1/9789241511124-eng.pdf?ua=1
. Published July 2016. Accessed January 3, 2017.
5. WHO issues new guidance on HIV self-testing ahead of World AIDS Day [news release]. Geneva, Switzerland: World Health Organization; November 29, 2016. http://www.who.int/mediacentre/news/releases/2016/world-aids-day/en/
. Accessed January 3, 2017.
6. Centers for Disease Control and Prevention, Association of Public Health Laboratories. Laboratory testing for the diagnosis of HIV infection: updates recommendations. CDC website. https://stacks.cdc.gov/view/cdc/23447
. Published June 27, 2014. Accessed January 3, 2017.
7. Health and Human Services, Health Resources and Services Administration. Guide for HIV/AIDS clinical care – 2014 edition. HHS website. http://hab.hrsa.gov/clinical-quality-management/clinical-care-guidelines-and-resources
. Published April 2014. Accessed January 5, 2017.
8. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. NIH website. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf
. Published July 14, 2016. Accessed January 5, 2017.
9. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2nd ed. WHO website. http://apps.who.int/iris/bitstream/10665/208825/1/9789241549684_eng.pdf?ua=1
. Published June 2016. Accessed January 5, 2017.
10. Centers for Disease Control and Prevention. Complete listing of medication adherence evidence-based behavioral interventions. CDC website. https://www.cdc.gov/hiv/research/interventionresearch/compendium/ma/complete.html
. Published November 16, 2016. Accessed January 5, 2017.
11. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. NIH website. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf
. Published November 10, 2016. Accessed January 6, 2017.