Highlights & Basics
- HIV infection is believed to have peaked in the late 1990s and to have stabilized recently. Globally, an estimated 38.4 million people were living with HIV at the end of 2021, with 1.5 million people newly infected.
- Most people are infected through sexual contact, before birth or during delivery, during breast-feeding, or when sharing contaminated needles and syringes.
- Diagnosis is established using an HIV antibody test and confirmed using a more specific test. Patients should be clinically staged according to World Health Organization or Centers for Disease Control and Prevention criteria.
- Guidelines recommend that all patients infected with HIV, regardless of CD4 cell count, should start antiretroviral therapy (ART) as soon as possible.
- Pre-exposure prophylaxis with daily oral antiretroviral therapy or long-acting intramuscular cabotegravir reduces the risk of HIV infection and is recommended in sexually active adults and people who inject drugs and who are at substantial ongoing risk of HIV exposure and acquisition.
- Diagnosis and management varies between resource-intensive settings and resource-limited settings.
Quick Reference
History & Exam
Key Factors
fevers and night sweats
weight loss
skin rashes and post-inflammatory scars
oral ulcers, angular cheilitis, oral thrush, or oral hairy leukoplakia
diarrhea
wasting syndrome
changes in mental status or neuropsychiatric function
recent hospital admissions
tuberculosis (TB)
medical comorbidities
sexual activity
generalized lymphadenopathy
Kaposi sarcoma
genital STIs
chronic vaginal candidiasis
shingles
headaches
periodontal disease
retinal lesions on fundoscopy
shortness of breath on exertion, cyanosis on exertion, dry cough, silent chest on auscultation
Other Factors
current and prior use of other substances
peripheral neuropathy
recurrent herpes simplex
hepatomegaly or splenomegaly
meningeal signs (bacterial or viral meningitis)
Diagnostics Tests
1st Tests to Order
serum HIV enzyme-linked immunosorbent assay (ELISA)
serum HIV rapid test
HIV noninvasive tests
serum Western blot
serum p24 antigen
serum HIV DNA polymerase chain reaction (PCR)
CD4 count
serum viral load (HIV RNA)
drug resistance testing
pregnancy test
serum hepatitis B serology
serum hepatitis C serology
CBC with differential
basic metabolic panel
urinalysis
liver function tests (LFTs)
random or fasting plasma glucose
lipid profile
human leukocyte antigen-B*5701 testing
Other Tests to consider
chest x-ray
hepatitis A serology (IgG)
toxoplasma serology (IgG)
testing for sexually transmitted infections
tuberculin skin test
Treatment Options
acute
newly confirmed infection
start antiretroviral therapy
select antiretroviral therapy regimen
supportive care
ongoing
virologic or immunologic treatment failure
reassessment of antiretroviral therapy
Definition
Classifications
HIV subtypes
- HIV type 1 (HIV 1) is the virus responsible for the global epidemic. There are three major groups within HIV 1: group M (major, which includes clades A, B, C, D, and L), N (non-M and non-O), and O (outlier). Clade B is the commonly occurring virus in Europe and the US. Clades A, C, and D predominate in Africa, clades B and AE (a circulating recombinant form) in Asia, and clade B in South America.[2] Globally, subtype C accounted for 46.6% of all HIV infections between 2010 and 2015, followed by subtype B (12.1%), subtype A (10.3%), subtype CRF02_AG (7.7%), subtype CRF01_AE (5.3%), subtype G (4.6%), subtype D (2.7%), and subtypes F, H, J, and K (0.9% combined).[5] Subtype L was discovered in 2019 from samples taken in the Democratic Republic of the Congo in 2001.[6] Subtype VB (virulent subtype B) was discovered in the Netherlands in 2022.[7]
Vignette
Common Vignette
Other Presentations
Epidemiology
Etiology
Pathophysiology
Diagnostic Approach
Establishing the diagnosis
Initial assessment
- During the acute seroconversion illness
- During an asymptomatic period of clinical latency
- During a symptomatic period of immune dysregulation and milder immune deficiency before the development of AIDS
- With severe immunodeficiency and AIDS.
History
- Home environment: type of housing, how many people live there, water and electricity supply
- Children: ages and HIV status if known
- Disclosure of HIV status: to sexual partner, family, and/or friends
- Support structures: people who can provide emotional support for the patient
- Employment
- Smoking history
- Exercise
- Current and prior use of alcohol or other substance use.
Clinical examination
- Weight and height measurement
- Examination for generalized lymphadenopathy, noting site, size, and mobility of nodes
- Skin inspection for HIV-associated rashes and scars (including herpes zoster), papular pruritic eruptions, fungal infections, or Kaposi sarcoma
- Examination of the mouth for oral thrush, oral hairy leukoplakia, Kaposi sarcoma, and periodontal disease
- Chest and cardiovascular examination for signs of, for example, pulmonic infection
- Abdominal examination to evaluate for hepatomegaly or splenomegaly
- Examination of the genitalia for signs of STIs (in all patients)
- Psychiatric assessment should include noting the patient's affect and orientation.
Laboratory testing at entry into care
- HIV antigen/antibody test
- HIV viral load
- CD4 count
- Genotypic resistance testing
- Hepatitis B and C screening
- Basic metabolic profile
- Liver function tests
- CBC with differential
- Lipid profile
- Random or fasting glucose
- Urinalysis
- Pregnancy testing.
Laboratory testing prior to ART initiation/modification
- HIV viral load
- CD4 count
- Genotypic resistance testing
- Tropism testing (if considering a CCR5 antagonist)
- HLAB*5701 testing (if considering abacavir)
- Hepatitis B serology (if switching to a regimen that does not contain tenofovir)
- Basic metabolic profile
- Liver function tests
- CBC with differential
- Random or fasting glucose
- Pregnancy test.
HIV testing
- ELISA: the most established tests for detecting HIV infection rely on ELISA as an initial screening test. During or shortly after infection, IgM antibodies to HIV first appear. This is followed weeks to months later by IgG antibodies to Gag and Env, and then to viral enzymes and regulatory proteins. The time to first detectable IgG by ELISA takes a median of 3 to 4 weeks, with almost all newly infected people having detectable IgG levels by 6 months. During this time an ELISA test may be falsely negative, a period known as the window period. Fourth-generation ELISA tests reduce the window period to about 2 to 4 weeks, thereby reducing the number of false-negative results, especially in areas where incident infections are common. The ELISA is the preferred screening method in the developing world since it lends itself to high throughput, rapid testing, and automation.
- Fourth-generation antibody (ELISA) and antigen (p24): the latest fourth-generation HIV tests incorporate the p24 antigen, meaning that obtaining a diagnosis of HIV during the window period is more likely, as the test examines both antibodies and the p24 antigen. This reduces the window period from 3 months to an average of 10 days; these tests may therefore be recommended for HIV confirmation.[80]
- Western blot: despite high specificity, the use of ELISA in populations where the prevalence of disease is low will lead to a high proportion of positive results being false. Thus, in the developed world, the protocol is to confirm positive or indeterminate ELISA results with a second test, the Western blot. Western blots require significant time and resources and so are not suited to many high-prevalence areas.
- Rapid test: this has worked well in resource-poor settings. Several have been endorsed by the US Food and Drug Administration and the WHO. These tests have higher than 99% sensitivity and specificity when combined with a confirmatory Western blot in the developed world and a second rapid test in the developing world.
- Other HIV screening tests: tests are available that detect the presence of HIV antibodies in fluids other than blood. Saliva has higher concentrations of IgA and IgG, and both ELISA and rapid tests exist for saliva.
- Nucleic acid testing (RNA or DNA): this provides the most sensitive test for HIV infection in the newborn, and can be used at 4 to 6 weeks of age. Placentally transferred maternal antibodies can persist in the neonate for up to 18 months, so antibody tests cannot be used to establish the diagnosis.
- Reverse-transcriptase PCR of viral RNA (viral load): this test measures active replication of HIV in blood and other body fluids, and is primarily used to assess activity of HIV and monitor the response to ART. There is an ultrasensitive version of this test that can reliably measure viral RNA levels as low as 20 RNA copies/mL of plasma. This is also the most sensitive test for adults with acute HIV infection who might be in a window period without detectable antibody or antigen (p24).
- p24 antigen: this is a core HIV protein and is present during high viral replication and so is detectable in the blood during acute infection and again during late stages of infection. Its use, therefore, is as a supplementary test during the window period. This test becomes positive later than HIV RNA (viral load) during acute HIV infection, and this is why it is less sensitive during this stage of infection.
CD4 count
Drug resistance testing
- With virologic failure and HIV RNA levels >200 copies/mL (drug resistance testing may be unsuccessful in patients with HIV RNA levels between 200 to 500 copies/mL, but should still be considered)
- With suboptimal viral load reduction.
Disease staging
Risk Factors
History & Exam
Tests
Differential Diagnosis
Infectious mononucleosis
Differentiating Signs/Symptoms
- Infection with Epstein-Barr virus (EBV) may resemble features of HIV acute seroconversion illness with fever, lymphadenopathy, pharyngitis, and maculopapular rash.
Differentiating Tests
- EBV: IgM serology and Paul Bunnell positive.
- HIV test negative.
Cytomegalovirus infection (CMV)
Differentiating Signs/Symptoms
- May resemble HIV acute seroconversion illness with fever, lymphadenopathy, rash, and splenomegaly.
Differentiating Tests
- CMV serology positive.
- HIV test negative.
Influenza infection
Differentiating Signs/Symptoms
- No specific differentiating signs; viral infections such as influenza may resemble acute seroconversion illness with fever, pharyngitis, and lymphadenopathy.
Differentiating Tests
- Influenza viral culture or nucleic acid test (nasopharyngeal or respiratory sample) positive
- HIV test negative.
Common cold
Differentiating Signs/Symptoms
- No specific differentiating signs; viral infections such as the common cold may resemble acute seroconversion illness with fever, pharyngitis, and lymphadenopathy.
Differentiating Tests
- HIV test negative.
Differentiating Signs/Symptoms
- Right upper quadrant abdominal pain, jaundice.
Differentiating Tests
- Elevated liver function tests.
- Hepatitis B or C serology positive.
- HIV test negative.
Secondary syphilis
Differentiating Signs/Symptoms
- Fever, malaise, pharyngitis, lymphadenopathy, maculopapular rash. Condylomata lata on genital areas and oral ulcers. May have been preceded by painless genital chancre and inguinal lymphadenopathy (primary syphilis). Can coexist with HIV.
Differentiating Tests
- Venereal disease research laboratory test positive.
- Treponema pallidum hemagglutination test positive.
- HIV test negative.
Coronavirus disease 2019 (COVID-19)
Differentiating Signs/Symptoms
- Residence in/travel to a country/area or territory with local transmission, or close contact with a confirmed or probable case of COVID-19, in the 14 days prior to symptom onset.
Differentiating Tests
- Real-time reverse transcription polymerase chain reaction (RT-PCR): positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA.
Criteria
- Acute seroconversion syndrome: there is no current case definition for acute seroconversion illness, although an acute viral syndrome in the early stages of HIV is well recognized. Primary infection usually presents within the first month of exposure to HIV and commonly presents with a fever and lymphadenopathy. Other clinical symptoms and signs might include pharyngitis, maculopapular rash, orogenital ulcers, or meningoencephalitis. Other opportunistic infections may occur, due to the transient lymphopenia. The CD4 count may drop profoundly. Diagnosis is made by observing the appearance of an HIV antibody (serial rapid tests or enzyme-linked immunosorbent assay [ELISA] or by noting the presence of HIV, using HIV-RNA or HIV-DNA and/or ultrasensitive HIV p24 antigen with an absent HIV antibody)[3] [22]
- Persistent generalized lymphadenopathy (painless enlarged nodes, in two or more noncontiguous sites of more than 1 cm for more than 3 months)
- Asymptomatic, that is, no symptoms reported that might be related to HIV/AIDS
- Performance status 1 (fully active and asymptomatic).
- Weight loss of less than 10% of body weight
- Herpes zoster (shingles)
- Minor mucocutaneous manifestations
- Recurrent upper respiratory tract infections
- Performance status 2 (symptomatic but near fully active).
- Weight loss of more than 10% of body weight
- Chronic diarrhea for more than 1 month
- Prolonged fever for more than 1 month
- Oral candida, chronic vaginal candidiasis
- Oral hairy leukoplakia
- Severe bacterial infections
- Pulmonary tuberculosis (TB)
- Performance status 3 (in bed less than 50% of past month).
- Extrapulmonary TB
- Pneumocystis jirovecii pneumonia
- Cryptococcal meningitis
- Herpes simplex virus ulcer for more than 1 month
- Esophageal or pulmonary candidiasis
- Toxoplasmosis
- Cryptosporidiosis
- Isosporiasis
- Cytomegalovirus
- HIV wasting syndrome
- HIV encephalopathy
- Kaposi sarcoma
- Progressive multifocal leukoencephalopathy
- Disseminated mycosis
- Atypical mycobacteriosis
- Nontyphoid salmonella bacteremia
- Lymphoma
- Recurrent pneumonia
- Invasive cervical carcinoma
- Performance status 4 (confined to bed more than 50% of the time).
- CD4 cell count <200 cells/microliter, or stage 3 or 4 event at presentation in adults, adolescents, and children ≥5 years of age. All children <5 years of age should be considered as having advanced disease at presentation.
- Seriously ill adult or adolescent: respiratory rate ≥30 breaths per minute, heart rate ≥120 bpm, unable to walk unaided, or body temperature ≥102.2°F (≥39°C).
- Seriously ill child: lethargy or unconsciousness, convulsions, unable to drink/breastfeed, repeated vomiting, tachycardia or tachypnea, or body temperature ≥102.2°F (≥39°C).
- Severely immunosuppressed: CD4 cell count <50 cells/microliter.
- Indicates early HIV infection, inferred from a negative or indeterminate HIV test result within 180 days of a positive result. The criteria for stage 0 supersede and are independent of criteria used for other stages.
- Laboratory confirmation of HIV infection with no AIDS-defining condition, and
- CD4+ T-lymphocyte count of ≥500 cells/microliter, or
- CD4+ T-lymphocyte percentage of total lymphocytes of ≥26%.
- Laboratory confirmation of HIV infection with no AIDS-defining condition, and
- CD4+ T-lymphocyte count of 200 to 499 cells/microliter, or
- CD4+ T-lymphocyte percentage of total lymphocytes of 14% to 25%.
- Laboratory confirmation of HIV infection, and
- CD4+ T-lymphocyte count of <200 cells/microliter, or
- CD4+ T-lymphocyte percentage of total lymphocytes of <14% or
- Documentation of an AIDS-defining condition.
Documentation of an AIDS-defining condition supersedes a CD4+ T-lymphocyte count of >200 cells/microliter and a CD4+ T-lymphocyte percentage of total lymphocytes of >14%.
- Laboratory confirmation of HIV infection, and
- No information on CD4+ T-lymphocyte count or percentage, and
- No information on presence of AIDS-defining conditions.
- Bacterial infections, multiple or recurrent (only among children ages <6 years)
- Candidiasis of bronchi, trachea, or lungs
- Candidiasis of esophagus
- Cervical cancer, invasive (only among adults, adolescents, and children ages ≥6 years)
- Coccidioidomycosis, disseminated, or extrapulmonary
- Cryptococcosis, extrapulmonary
- Cryptosporidiosis, chronic intestinal (>1 month's duration)
- Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age >1 month
- Cytomegalovirus retinitis (with loss of vision)
- Encephalopathy, HIV-related
- Herpes simplex: chronic ulcers (>1 month's duration) or bronchitis, pneumonitis, or esophagitis (onset at age >1 month)
- Histoplasmosis, disseminated or extrapulmonary
- Isosporiasis, chronic intestinal (>1 month's duration)
- Kaposi sarcoma
- Lymphoma, Burkitt (or equivalent term)
- Lymphoma, immunoblastic (or equivalent term)
- Lymphoma, primary, of brain
- Mycobacterium avium complex or Mycobacterium kansasii, disseminated or extrapulmonary
- Mycobacterium tuberculosis of any site, pulmonary (only among adults, adolescents, and children ages ≥6 years), disseminated, or extrapulmonary
- Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
- Pneumocystis jirovecii pneumonia
- Pneumonia, recurrent (only among adults, adolescents, and children ages ≥6 years)
- Progressive multifocal leukoencephalopathy
- Salmonella septicemia, recurrent
- Toxoplasmosis of brain, onset at age >1 month
- Wasting syndrome attributed to HIV.
Screening
HIV screening
- When someone requests a test
- When someone has a condition that indicates possible HIV infection
- When someone believes that they are at risk of infection through unprotected sexual activity, needle stick injury, or unsafe injection drug use
- In all pregnant women
- For public health and infection control (e.g., blood product safety)
- When required by, for example, life insurers.
Treatment Approach
Initial care and counseling
- Risk reduction counseling in HIV-positive people has been shown to be effective in reducing further transmission of HIV. This is particularly important during acute or primary HIV infection when plasma HIV levels are high and the patient is highly infectious. More than one session of counseling may be needed to result in a change in high-risk sexual behavior. Referral should be made to appropriate counselor/support groups for ongoing counseling sessions.[20] [105]
- Counseling before initiating ART should focus on preparing the patient to commit to long-term ART. Adherence to ART should be regularly assessed at every clinic visit.[71]
- One Cochrane review found that simple ART adherence measures (e.g., self-reporting measures, tablet counts, electronic monitoring, pharmacy records) did not help identify patients who might not be taking their medications and who had higher viral loads. No one modality consistently offered a sufficiently high sensitivity to detect viral non‐suppression across groupings of similar measures.[106]
- Concomitant and opportunistic infections are common in HIV-infected patients.
- Primary prophylaxis against opportunistic infections including TB, Pneumocystis jirovecii, Mycobacterium avium complex, toxoplasmosis, and malaria (if required) is recommended.[107]
- Malnutrition is common in HIV disease, particularly in resource-poor areas. A cycle of opportunistic infection causing loss of weight and poor appetite, together with diarrhea and malabsorption, contributes to this malnutrition. Management would include ensuring an adequate balanced food source and early identification and management of OIs.[108] [109]
- If the patient has concurrent hepatitis B infection, appropriate treatment should be used as part of ART. All patients with hepatitis C and HIV co-infection require treatment according to the latest guidance.
- See HIV-related opportunistic infections .
- Routine primary prevention for chronic diseases of aging is recommended based on age and risk. This includes risk assessment, screening, and testing for age-appropriate conditions such as cardiovascular disease, liver disease, diabetes, cancers, and bone disease. Assessment of diet, physical activity, smoking status, alcohol abuse, and substance abuse should be included.
- There is limited evidence of consistent clinically important benefits with micronutrient supplementation; however, most practitioners add a multivitamin and mineral combination supplement containing vitamins A, B6, B12, C, D, E and folate, with calcium, magnesium, iron, zinc, and selenium.[110] [111] There is some evidence that selenium supplementation can delay CD4 cell decline in HIV-infected patients; however, there is no quantifiable evidence that it reduces viral load.[112]
- Data on the benefits of omega-3 fatty acids supplementation are controversial, but some studies show that they may decrease serum inflammatory markers (e.g., C-reactive protein).[113]
- Vaccines should be given as early as possible in HIV infection or once the immune system has recovered on ART, as immune responses decrease with increased immunosuppression.
- Recommended vaccinations include pneumococcal (pneumonia), meningococcal, influenza, hepatitis B, human papillomavirus, and tetanus/diphtheria/pertussis.[114] The herpes zoster vaccine is also recommended in people ages ≥18 years. All people with HIV infection should receive a COVID-19 vaccine according to your local immunization schedule, regardless of their CD4 count or viral load.[107] Additional vaccinations (e.g., hepatitis A, measles/mumps/rubella, varicella, typhoid, yellow fever) may be recommended depending on the patient's age, risk factors for a specific disease, and previous vaccination history. Current local immunization schedules should be consulted.[114]
- Other vaccines may be recommended in travelers depending on the risk of acquiring a given disease in the area of travel (e.g., Japanese B encephalitis, inactivated typhoid, yellow fever, inactivated polio).
- Live vaccines are generally contraindicated, particularly if immune compromise has already occurred. The measles-mumps-rubella (MMR) vaccine, varicella live vaccine, and herpes zoster live vaccine are contraindicated in patients with a CD4 count <200 cells/microliter. Other contraindicated vaccines include the Bacillus Calmette-Guérin (BCG), oral polio, typhoid, and yellow fever vaccines.
Starting antiretroviral therapy
- The strength of this recommendation was reinforced by the Strategic Timing of AntiRetroviral Treatment (START) study, which found that the risk of developing serious illness or death was reduced by 53% among those in the early treatment group, compared with those in the deferred treatment group.[115]
- World Health Organization (WHO) guidelines support the recommendation to initiate ART in all patients living with HIV, regardless of CD4 count.[45]
- The WHO recommends that rapid ART initiation (i.e., within 7 days of diagnosis, preferably on the same day as diagnosis in patients who are willing and ready to start treatment and there is no clinical contraindication) should be offered to all people living with HIV following a confirmed diagnosis and clinical assessment.[88]
- One Cochrane review of seven randomized controlled trials (RCTs) with more than 18,000 adults found that rapid initiation (within 7 days of diagnosis) of ART probably results in greater viral suppression at 12 months compared with standard initiation in low- and middle-income settings.[116]
- Rapid initiation of ART may be difficult to achieve in resource-limited settings.
Choice of antiretroviral therapy
- Nucleoside reverse transcriptase inhibitors (NRTIs)
- Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
- Protease inhibitors (PIs)
- Integrase strand transfer inhibitors (INSTIs)
- Pharmacokinetic enhancers or boosters (improve pharmacokinetic profiles of some antiretrovirals and increase their effectiveness, resulting in lower doses of the antiretroviral being needed).
- Local infectious disease specialists or HIV practitioners should be consulted and preferably patients referred to them for further management.
- Given the number of effective options for initial therapy, selection of a regimen for a particular patient should be guided by factors such as virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance testing results, comorbid conditions, and cost.[71]
- INSTI-based regimens:
- Bictegravir plus tenofovir alafenamide plus emtricitabine
- Dolutegravir plus abacavir plus lamivudine (only for human leukocyte antigen [HLA]-B*5701 negative patients)
- Dolutegravir plus tenofovir plus lamivudine or emtricitabine.
- Long-acting cabotegravir has a long half-life and drug levels may persist in some people for up to 4 years at a suboptimal level, which may select for INSTI-resistant virus.
- INSTI resistance may be present in those who become infected during (and possibly after) the use of long-acting cabotegravir. Therefore, INSTI genotypic resistance testing is recommended before starting ART, regardless of the amount of time since drug discontinuation.
- INSTI-based regimens should not be started unless genotype tests show no INSTI-resistance mutations.
- If treatment is started before results are obtained, the following non-INSTI regimen is recommended pending genotype results:
- Ritonavir- or cobicistat-boosted darunavir plus tenofovir plus lamivudine or emtricitabine.
- If an INSTI-based regimen is initiated and viral suppression is not achieved within 8 to 12 weeks, genotypic resistance testing (including for INSTIs) should be repeated.
- A combination formulation of dolutegravir/lamivudine has been approved in the US and Europe as a complete regimen for the treatment of HIV-1 infection in adults with no ART history.
- INSTI-based regimens:
- Elvitegravir plus cobicistat plus tenofovir plus emtricitabine
- Raltegravir plus tenofovir plus lamivudine or emtricitabine.
- PI-based regimens:
- Ritonavir- or cobicistat-boosted darunavir plus tenofovir plus lamivudine or emtricitabine
- Ritonavir- or cobicistat-boosted atazanavir plus tenofovir plus lamivudine or emtricitabine
- Ritonavir- or cobicistat-boosted darunavir plus abacavir plus lamivudine (only for patients who are HLA-B*5701 negative).
- NNRTI-based regimens:
- Doravirine plus tenofovir plus lamivudine or emtricitabine
- Efavirenz plus tenofovir plus lamivudine or emtricitabine
- Rilpivirine plus tenofovir plus emtricitabine (only for patients with HIV RNA <100,000 copies/mL and CD4 cell count >200 cells/microliter).
- Bictegravir plus tenofovir alafenamide plus emtricitabine
- Dolutegravir plus tenofovir plus lamivudine
- Ritonavir- or cobicistat-boosted darunavir plus tenofovir plus lamivudine or emtricitabine.
- Ritonavir-boosted darunavir plus raltegravir (only for patients with HIV RNA <100,000 copies/mL and CD4 count >200 cells/microliter)
- Ritonavir-boosted darunavir plus lamivudine.
- Other guidelines may recommend different regimens; however, most agree that second-generation INSTIs (bictegravir and dolutegravir) now offer the most advantages for the treatment of HIV and are generally a first-line option when available. The WHO supports the use of a dolutegravir-based regimen first-line, with efavirenz-based regimens recommended as a suitable alternative.[121]
- Tenofovir is available as tenofovir disoproxil fumarate or the oral prodrug tenofovir alafenamide. Tenofovir alafenamide is available only in fixed-dose combination formulations with other antiretroviral agents. The prodrug is associated with less renal toxicity and less of an effect on bone mineral density, while tenofovir disoproxil fumarate is associated with lower lipid levels.[71] [122] [123]
- Preliminary data from a birth outcomes surveillance study in Botswana raised concern of an increased risk of neural tube defects (0.9%) in infants born to women who were receiving dolutegravir at the time of conception. However, updated results from the study have shown that the prevalence of neural tube defects in infants who were exposed to dolutegravir at the time of conception is not significantly different from those on non-dolutegravir-based regimens.
- For people with pretreatment drug resistance to NNRTIs, or people at high risk of pretreatment drug resistance to NNRTIs because of prior exposure to NNRTIs or from other risks, a non-NNRTI-containing regimen may be preferable. As individual level drug resistance testing isn't available in most low- and middle-income countries, nationally representative data may be used.[124]
- A regimen may be switched, for example, to simplify regimens, enhance tolerability, decrease toxicity, prevent drug interactions, and reduce costs. The aim is to maintain viral suppression without jeopardizing future treatment options.
- The patient's ART history should be reviewed, and any past instances of treatment failure and drug resistance should be taken into account when selecting a new regimen.
- A three-drug regimen is usually recommended; however, there is emerging evidence that a two-drug regimen may also maintain virologic suppression. The Food and Drug Administration has approved dolutegravir/rilpivirine to treat adults with HIV-1 infection whose virus is currently suppressed on a stable regimen for at least 6 months, with no history of treatment failure and no known substitutions associated with resistance to the individual components. Monotherapy is not recommended.
- A specialist should be consulted before switching regimens.
Failure of first-line regimen
Non-AIDS-defining comorbidities
Treatment Options
newly confirmed infection
start antiretroviral therapy
Comments
- Antiretroviral therapy (ART) is recommended for all HIV-infected patients, including those with acute or primary HIV infection, regardless of CD4 count as it has been shown to reduce the risk of disease progression, decrease comorbid disease, and prevent HIV transmission.[71] The strength of this recommendation was reinforced by the Strategic Timing of AntiRetroviral Treatment (START) study, which found that the risk of developing serious illness or death was reduced by 53% among those in the early treatment group, compared with those in the deferred treatment group.[115] World Health Organization (WHO) guidelines support the recommendation to initiate ART in all patients living with HIV, regardless of CD4 count.[45]
- ART should be started immediately (as soon as possible) after HIV diagnosis in order to increase the uptake of ART and linkage to care, decrease the time to viral suppression, reduce the risk of transmission, and improve the rate of virologic suppression.[71] The WHO recommends offering rapid ART initiation to all people living with HIV following a confirmed diagnosis and clinical assessment, in patients who are willing and ready to start treatment, and where there is no clinical contraindication.[88] Rapid ART initiation is defined as within 7 days of diagnosis, preferably on the same day as diagnosis. One Cochrane review of seven randomized controlled trials with more than 18,000 adults found that rapid initiation (within 7 days of diagnosis) of ART probably results in greater viral suppression at 12 months compared with standard initiation in low- and middle-income settings.[116] Rapid initiation of ART may be difficult to achieve in resource-limited settings.
- Although ART has long-term adverse effects, these are minimal compared with complications of untreated HIV infection.
select antiretroviral therapy regimen
Primary Options
INSTI-based regimen
bictegravir/emtricitabine/tenofovir alafenamide
INSTI-based regimen
dolutegravirand
- abacavir
and
- lamivudine
INSTI-based regimen
dolutegravirAND
- tenofovir disoproxil
or
- tenofovir alafenamide
AND
- lamivudine
or
- emtricitabine
INSTI-based two-drug regimen
dolutegravir/lamivudine
Secondary Options
INSTI-based regimen
elvitegravirand
- cobicistat
and
- emtricitabine
AND
- tenofovir disoproxil
or
- tenofovir alafenamide
INSTI-based regimen
raltegravirAND
- tenofovir disoproxil
or
- tenofovir alafenamide
AND
- lamivudine
or
- emtricitabine
PI-based regimen
darunavirAND
- ritonavir
or
- cobicistat
AND
- tenofovir disoproxil
or
- tenofovir alafenamide
AND
- lamivudine
or
- emtricitabine
PI-based regimen
atazanavirAND
- ritonavir
or
- cobicistat
AND
- tenofovir disoproxil
or
- tenofovir alafenamide
AND
- lamivudine
or
- emtricitabine
PI-based regimen
darunavirAND
- ritonavir
or
- cobicistat
AND
- abacavir
AND
- lamivudine
NNRTI-based regimen
doravirineAND
- tenofovir disoproxil
or
- tenofovir alafenamide
AND
- lamivudine
or
- emtricitabine
NNRTI-based regimen
efavirenzAND
- tenofovir disoproxil
or
- tenofovir alafenamide
AND
- lamivudine
or
- emtricitabine
NNRTI-based regimen
rilpivirineAND
- tenofovir disoproxil
or
- tenofovir alafenamide
AND
- emtricitabine
Comments
- The choice of effective drug combinations in treatment-naive patients requires expertise, particularly in complex cases. Treatment is best individualized by a clinician who is experienced in HIV management.
- In most regions, a first-line antiretroviral therapy regimen will generally consist of two nucleoside reverse transcriptase inhibitors (NRTIs) in combination with a third agent (usually an integrase strand transfer inhibitor [INSTI], or a nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]).[71] [117] [118] Some guidelines now also recommend a two-drug regimen of an INSTI plus an NRTI (e.g., dolutegravir plus lamivudine) as an initial regimen.[71] Regimens recommended by the US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents are detailed here.[71] Other guidelines may recommend different regimens.
- A different regimen may be recommended for people with HIV and a history of using long-acting cabotegravir as pre-exposure prophylaxis (PrEP). INSTI genotypic resistance testing is recommended in these patients before starting ART, regardless of the amount of time since drug discontinuation. INSTI-based regimens should not be started unless genotype tests show no INSTI-resistance mutations. If treatment is started before results are obtained, the following non-INSTI regimen is recommended pending genotype results: ritonavir- or cobicistat-boosted darunavir plus tenofovir plus lamivudine or emtricitabine.[71]
- Discuss the risks and benefits of using a dolutegravir-based regimen in people of childbearing potential who are trying to conceive, to allow them to make an informed decision. Preliminary data from a birth outcomes surveillance study in Botswana raised concern of an increased risk of neural tube defects (0.9%) in infants born to women who were receiving dolutegravir at the time of conception. However, updated results from the study have shown that the prevalence of neural tube defects in infants who were exposed to dolutegravir at the time of conception is not significantly different from those on non-dolutegravir-based regimens.[71]
- Consider the potential for drug-drug interactions (including over-the-counter and complementary or alternative medicines) when prescribing or switching one or more drugs in an ART regimen. Drug-drug interactions between ART regimens and concomitant medications are common, and may affect therapeutic responses.[71]
- A specialist should be consulted for further guidance on regimens and doses. Regimens and doses may differ in children and adolescents, older people, patients with hepatic/renal impairment or other comorbidities or coinfections, and pregnant/breastfeeding women and are beyond the scope of this topic.
- Patients must be ready to adhere to treatment, and their readiness should be established through counseling. Fixed-dose combination tablets that combine two or three classes of drugs in one tablet (or two drugs from the same class) are available, and can assist in improving medication compliance.
- Once virologic suppression is achieved, regimen switching (within or between a class of drugs) may be considered in some patients, provided there is no evidence of viral resistance to the drugs in the new regimen. A specialist should be consulted before switching regimens.[71]
supportive care
Comments
- Counseling: risk reduction counseling in HIV-positive people has been shown to be effective in reducing further transmission of HIV. More than one session of counseling may be needed. Referral should be made to appropriate counselor/support groups for ongoing counseling sessions.[20] [105] Counseling before initiating antiretroviral therapy (ART) should focus on preparing the patient to commit to long-term ART. Adherence to ART should be regularly assessed at every clinic visit.[71] One Cochrane review found that simple ART adherence measures (e.g., self-reporting measures, tablet counts, electronic monitoring, pharmacy records) did not help identify patients who might not be taking their medications and who had higher viral loads. No one modality consistently offered a sufficiently high sensitivity to detect viral non‐suppression across groupings of similar measures.[106]
- Prophylaxis of opportunistic infections: primary prophylaxis against opportunistic infections including tuberculosis, Pneumocystis jirovecii, Mycobacterium avium complex, toxoplasmosis, and malaria (if required) is recommended.[107] Early identification and management of opportunistic infections is extremely important. See HIV-related opportunistic infections .
- Other infections: patients with concomitant hepatitis B or C should be treated according to latest guidance.
- Comorbidities: routine primary prevention for chronic diseases of aging is recommended based on age and risk (e.g., risk assessment, screening, and testing for age-appropriate conditions such as cardiovascular disease, liver disease, diabetes, cancers, and bone disease). Assessment of diet, physical activity, smoking status, alcohol abuse, and substance abuse should be included.
- Micronutrient supplementation: there is limited evidence of consistent clinically important benefits with micronutrient supplementation; however, most practitioners add a multivitamin and mineral combination supplement containing vitamins A, B6, B12, C, D, E, and folate, with calcium, magnesium, iron, zinc, and selenium.[110] [111] There is some evidence that selenium supplementation can delay CD4 cell decline in HIV-infected patients; however, there is no quantifiable evidence that it reduces viral load.[112]
- Vaccinations: recommended vaccinations include pneumococcal (pneumonia), meningococcal, influenza, hepatitis B, human papillomavirus, and tetanus/diphtheria/pertussis.[114] The herpes zoster vaccine is also recommended in people ages ≥18 years. All people with HIV infection should receive a COVID-19 vaccine according to your local immunization schedule, regardless of their CD4 count or viral load.[107] Additional vaccinations (e.g., hepatitis A, measles/mumps/rubella, varicella, typhoid, yellow fever) may be recommended depending on the patient's age, risk factors for a specific disease, and previous vaccination history. Current local immunization schedules should be consulted.[114] Live vaccines are generally contraindicated.
virologic or immunologic treatment failure
reassessment of antiretroviral therapy
Comments
- Virologic failure is defined as the inability to achieve or maintain suppression of viral replication to an HIV RNA level <200 copies/mL.[71]
- Patients with virologic failure should be referred back to an HIV-experienced clinician or infectious diseases specialist for further drug-resistance testing, adherence assessment, and optimization of their treatment regimens based on drug resistance patterns.[71]
- Immunologic failure is the failure to achieve and maintain an adequate CD4 response despite virologic suppression.[125] These patients should also be referred to their specialist for assessment of current medications, untreated co-infections, and serious medical conditions.
- First-line INSTI-based regimens were associated with a lower risk of virologic failure compared with PI-based regimens in one study. However, both INSTI- and PI-based regimens were associated with a higher risk of virologic failure compared with NNRTI-based regimens, potentially due to channeling bias whereby nonadherent patients may have been more likely to be initiated on INSTI- or PI-based ART first line.[126]
- Assessing and managing a patient who is experiencing ART failure can be complex. Detailed information on the management of treatment-experienced patients is beyond the scope of this topic, and treatment-experienced patients should be managed by a specialist.
Emerging Tx
Cabotegravir and rilpivirine
Ibalizumab
Lenacapavir
Fostemsavir
PRO 140
Other antiviral therapies
Gene therapies
NK cell-based therapies
Prevention
Primary Prevention
- The most widely available tool for prevention of HIV infection during sexual intercourse is the male condom. Male condoms afford a high degree of protection: consistent and correct male condom use reduces HIV transmission by more than 90%.[37] Numerous studies have shown that the female condom is an acceptable method for many women and men, and is a valuable alternative for women whose partners refuse to use male condoms. Unlike the male condom, the female condom can be inserted some time before sex, and does not depend on the same degree of male cooperation for its successful use.
- Studies have shown the effectiveness of daily oral PrEP in reducing the risk of HIV infection in adults who are at high risk for HIV acquisition.
- Evidence from randomized controlled trials shows that oral tenofovir/emtricitabine prophylaxis is highly effective in reducing the risk of HIV acquisition (75% to 86% reduction in the risk of HIV in MSM, depending on adherence level), and is considered safe with minimal adverse effects, in MSM, serodiscordant couples, and people who inject drugs.[40] [41]
- However, data from observational studies found that efficacy appears to be lower in real-world settings (60% reduction in the risk of HIV overall), possibly due to suboptimal PrEP adherence and interruptions to treatment supply, particularly among people <30 years of age and those who were socioeconomically deprived.[42]
- The largest real-world study involving over 24,000 trial participants at sexual health clinics and conducted over three years found that the use of oral PrEP reduced the risk of getting HIV by 86% in real-world settings.[43]
- There are data that provide reassurance that resistance is unlikely to occur in patients taking PrEP.[44]
- Guideline recommendations for the use of oral PrEP vary. Consult your local guidelines for further information.
- The World Health Organization strongly recommends offering oral PrEP (containing tenofovir) as an additional prevention choice to people who are at substantial risk of HIV infection, as part of combination prevention approaches, based on high-certainty evidence.[45]
- The Centers for Disease Control and Prevention (CDC) recommends daily oral PrEP with tenofovir/emtricitabine as a prevention option for: sexually active adults who report sexual behaviors that place them at substantial ongoing risk of HIV exposure and acquisition; and adults who inject drugs and report injection practices that place them at substantial ongoing risk of HIV exposure and acquisition. However, all sexually active adults and adolescents should be informed about PrEP for prevention of HIV acquisition. Tenofovir disoproxil is recommended for both men and women; however, tenofovir alafenamide is recommended in men and transgender women only (it has not been studied in women as yet). The safety and efficacy of other daily oral antiretroviral medications for PrEP have not been studied extensively and are not currently recommended. HIV infection should be assessed at least every 3 months so that people with incident infection do not continue taking it.[46]
- The American College of Obstetricians and Gynecologists (ACOG) supports CDC guidance, and recommends that obstetricians and gynecologists discuss PrEP with all sexually active adolescent and adult patients, not only those who are considered to be a substantial risk of HIV infection.[47]
- The US Preventive Services Task Force recommends oral PrEP (i.e., tenofovir/emtricitabine) in high-risk adolescents and adults. This includes sexually active adolescents and adults who have engaged in anal or vaginal sex in the past 6 months and have any of the following: a sexual partner who has HIV; a bacterial sexually-transmitted infection in the past 6 months; a history of inconsistent (or no) condom use with sex partner(s) whose HIV status is unknown. It also includes people who inject drugs and have a drug-injecting partner who has HIV or shares injection equipment. People who engage in transactional sex and transgender women should be considered for PrEP based on these criteria.[48]
- Acute and chronic HIV infection must be excluded by symptom history and HIV testing immediately before any PrEP regimen is prescribed. Renal function should be assessed at baseline and monitored periodically during treatment.[46]
- Regular STI testing and risk reduction counseling is recommended for MSM who use PrEP.[46]
- Cabotegravir extended-release injectable suspension is approved in some countries for use in at-risk adults for pre-exposure prophylaxis to reduce the risk of sexually-acquired HIV infection.[53]
- Injections are administered every 2 months after the initial dose (two injections one month apart).
- Patients can either start on intramuscular cabotegravir or take oral cabotegravir before switching to the intramuscular formulation to assess their tolerance of the drug.
- A negative HIV test is required before treatment is started, and before each injection, in order to reduce the risk of developing drug resistance.
- Long-acting injectable PrEP may address issues with adherence, and could be an important prevention intervention for certain HIV populations.[54]
- Long-acting injectable cabotegravir was found to lower HIV incidence compared to daily oral tenofovir/emtricitabine when used for PrEP among men who have sex with men, transgender women, and cisgender women in sub-Saharan Africa in clinical trials.[55]
- The WHO recommends long-acting cabotegravir as an additional prevention choice for people at substantial risk of HIV infection, as part of combination prevention approaches, based on moderate-certainty evidence.[56]
- The Centers for Disease Control and Prevention recommends intramuscular cabotegravir injections as PrEP in adults who report sexual behaviors that place them at substantial ongoing risk of HIV exposure and acquisition.[46]
- The US Preventive Services Task Force recommends intramuscular cabotegravir injections as an option for PrEP in high-risk adolescents and adults (see above for criteria).[48]
- Hepatotoxicity has been reported in a small number of people receiving cabotegravir, although similar levels were found among those receiving placebo. Consider liver function testing before and during treatment, and do not initiate treatment in people with advanced liver disease or acute viral hepatitis. Discontinue use if hepatotoxicity is confirmed. There are limited data on the use of cabotegravir in patients with hepatitis B or hepatitis C virus infection, and caution is advised.[56]
- Consult your local drug formulary for more information before prescribing long-acting injectable PrEP.
- Pericoital (on-demand) PrEP may be considered instead of daily PrEP in MSM who have infrequent sexual exposures.
- On-demand PrEP has been found to be effective in MSM who are at a high risk of HIV infection. However, a post-hoc analysis of the ANRS IPERGAY trial found that on-demand PrEP was also effective in MSM who were at a lower risk of HIV infection (i.e., periods of less frequent sexual intercourse defined as 5 episodes per month), with a 100% relative reduction of HIV incidence reported compared with placebo.[57]
- The dapirivine vaginal ring is approved for use in some countries with high disease burden to reduce the risk of infection, in combination with safer sex practices, when oral PrEP is not used, cannot be used, or is not available. The ring is placed in the vagina and slowly releases dapivirine over a period of 28 days.
- Current evidence shows that vaginal dapivirine microbicide probably reduces HIV acquisition in women who have sex with men. Other types of vaginal microbicides have not shown evidence of an affect on HIV acquisition.[58]
- A systematic review of 18 randomized controlled trials in sub-Saharan Africa found that the dapivirine intravaginal ring reduced the risk of HIV transmission in women by 29%. Other microbicides had no effect.[59]
- In a randomized, double-blind, placebo-controlled, phase 3 trial in sub-Saharan Africa, the dapivirine vaginal ring was associated with a lower rate of HIV acquisition compared with placebo.[60]
- Guideline recommendations for the use of dapivirine vaginal ring vary. Consult your local guidelines for further information.
- The WHO recommends the dapivirine vaginal ring may be offered as an additional prevention choice for women at substantial risk of HIV infection, and part of combination prevention approaches, based on moderate-certainty evidence.[61]
- Tenofovir-based microbicide gel has also been reported to reduce rates of HIV transmission to women.[62]
- Consult your local drug formulary for more information before prescribing dapivirine vaginal ring.
- Based on high-quality evidence, there is a negligible risk of sexual transmission of HIV when an HIV-positive sex partner adheres to ART and maintains a suppressed viral load <200 copies/mL measured every 4 to 6 months. Sexual transmission of HIV has occurred when viral load was >200 copies/mL with ART or condoms alone were used, although the risk remains low.[69] One systematic review found that the risk of sexual transmission in people with viral loads between 200 copies/mL and 1000 copies/mL is almost zero.[70]
- In light of this evidence, US guidelines recommend that physicians should inform patients that maintaining a HIV RNA level <200 copies/mL with ART prevents transmission to sexual partners. Another form of prevention should be used for the first 6 months of ART until an HIV RNA level of <200 copies/mL has been documented, with some experts recommending that sustained suppression is confirmed before assuming there is no risk of transmission.[71]
- The Prevention Access Campaign has also released a consensus statement stating that the risk of HIV transmission from a person living with HIV who is on ART and has achieved undetectable viral load in their blood for at least 6 months is negligible to nonexistent.Prevention Access Campaign: consensus statement
- Convincing evidence exists for the benefit of needle exchange and clean syringes in the setting of methadone clinics, termed "harm reduction," where HIV transmission risk is related to shared intravenous drug use equipment. In addition, the supply of HIV-free blood and blood products, as well as sterile needles and syringes for injections and universal precautions in hospitals, has much reduced nosocomial transmission of HIV.[75]
Secondary Prevention
- Sexual contacts of the patient should be inquired about. HIV status may already be known. If not, disclosure should be discussed. Patients may not be able to do this immediately but should be encouraged, especially in a situation where disclosure is linked to being able to practice safer sex. Practitioners may also offer to assist with disclosure under these circumstances and offer immediate testing for partners. There may be local regulations, and physicians should refer to these where appropriate. Public health officers may be able to facilitate partner notification.
- The physician should inquire whether the patient has children and how old they are. Their well-being and medical histories may give a clue to possible infection (if not already tested). If younger than 10 years of age and well and not previously tested, the physician may also advise having them tested. Children younger than 18 months of age may need a nucleic acid test (qualitative polymerase chain reaction). If still breast-feeding, advice against ongoing transmission risk should be given and consideration to weaning (if older than 6 months of age) or switching to bottle/formula feeding.[205]
Follow-Up Overview
Prognosis
Virologic suppression
Mortality
Remission or cure
Monitoring
- CD4 cell count: every 3 months (if CD4 count <300 cells/microliter) or 6 months (if CD4 count is ≥300 cells/microliter) during the first 2 years. After 2 years on ART with consistently suppressed viral load, monitor every 6 months (CD4 count remains <300 cells/microliter), 12 months (CD4 count consistently 300-500 cells/microliter), or optional (CD4 count consistently ≥500 cells/microliter). Also recommended if treatment failure, clinically indicated, or every 3-6 months if ART is delayed.
- HIV viral load: 4-8 weeks after ART initiation/modification. If HIV RNA is detectable at 4-8 weeks, repeat testing every 4-8 weeks until viral load is suppressed to <50 copies/mL. Thereafter, repeat testing every 3-6 months (every 3 months during the first 2 years of ART, then can extend to every 6 months for patients with consistent viral suppression ≥2 years). More frequent monitoring may be considered in individuals who are having difficulties with ART adherence. Also recommended if treatment failure, clinically indicated, or if ART is delayed (repeat testing is optional).
- Resistance testing (reverse transcriptase and protease genes): only recommended if treatment failure, clinically indicated, or if ART is delayed.
- Resistance testing (integrase genes): only recommended if treatment failure or clinically indicated (if there is a history of integrase strand transfer inhibitor use).
- Tropism testing: only recommended if treatment failure (if considering a CCR5 antagonist or patients with virologic failure on a CCR5 antagonist) or clinically indicated.
- Hepatitis B screening: if clinically indicated only (e.g., before starting direct-acting antivirals for hepatitis C virus infection).
- Basic metabolic panel: 4-8 weeks after ART initiation/modification, and then every 6 months. Also recommended if clinically indicated or every 6-12 months if ART is delayed.
- Liver function tests: 4-8 weeks after ART initiation/modification, and then every 6 months. Also recommended if clinically indicated or every 6-12 months if ART is delayed.
- Complete blood count with differential: every 3-6 months initially (when monitoring CD4 count), and then every 12 months (when no longer monitoring CD4 count). Also recommended if clinically indicated.
- Lipid profile: consider 1-3 months after ART initiation or modification, and then every 12 months (if normal at baseline but with cardiovascular risk). Also recommended if clinically indicated (if normal at baseline, every 5 years if clinically indicated).
- Random or fasting glucose level: if clinically indicated or treatment failure.
- Urinalysis: if clinically indicated only (e.g., patients with diabetes mellitus or chronic kidney disease).
- Pregnancy test: if clinically indicated only.
Complications
Citations
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US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Feb 2024 [internet publication].[Full Text]
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. Geneva, Switzerland: WHO Press; 2007 [internet publication].[Full Text]
World Health Organization. Update of recommendations on first- and second-line antiretroviral regimens. Jul 2019 [internet publication].[Full Text]
- UNAIDS global AIDS update 2022
- Prevention Access Campaign: consensus statement
- CDC: HIV self-testing
- BMJ practice article: two-drug antiretroviral regimens for HIV
- University of Liverpool: HIV drug interactions
- AIDSinfo: antiretroviral agents in HIV-1-infected adults and adolescents
- FDA: HIV treatment information for adults
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192. Chan P, Brew BJ. HIV associated neurocognitive disorders in the modern antiviral treatment era: prevalence, characteristics, biomarkers, and effects of treatment. Curr HIV/AIDS Rep. 2014 Sep;11(3):317-24.[Abstract]
193. Wang Y, Liu M, Lu Q, et al. Global prevalence and burden of HIV-associated neurocognitive disorder: a meta-analysis. Neurology. 2020 Nov 10;95(19):e2610-21.[Abstract]
194. Eshun-Wilson I, Siegfried N, Akena DH, et al. Antidepressants for depression in adults with HIV infection. Cochrane Database Syst Rev. 2018 Jan 22;(1):CD008525.[Abstract][Full Text]
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Key Articles
Other Online Resources
Referenced Articles
Guidelines
Diagnostic
Summary
Provides recommendations on initial baseline evaluation of HIV-infected patients. Initial HIV testing, laboratory evaluation of CD4 count, viral load, and further tests performed in the setting of drug resistance or sensitivity are discussed. Laboratory monitoring during treatment is described.Published by
US Department of Health and Human Services
Published
2024
Summary
Chapter includes diagnosis of HIV infection.Published by
Centers for Disease Control and Prevention
Published
2023
Summary
Information on diagnosis and management of HIV and counseling of HIV-infected patients.Published by
Centers for Disease Control and Prevention
Published
2021
Summary
This guideline is to be used in conjunction with the Centers for Disease Control and Prevention's Laboratory testing for the diagnosis of HIV infection: updated recommendations guideline from 2015 (see below).Published by
Centers for Disease Control and Prevention
Published
2018
Summary
Updates recommendations for HIV testing by laboratories in the US. Should be used in conjunction with the 2018 updated algorithm (above).Published by
Centers for Disease Control and Prevention
Published
2014
Summary
These guidelines bring together existing guidance relevant to the provision of HIV testing services.Published by
World Health Organization
Published
2021
Treatment
Summary
Provides guidelines on the indications to initiate antiretroviral therapy and also discusses important aspects of care in certain populations such as hepatitis B- or C-infected patients, those with renal disease, adolescents, and intravenous drug users. Antiretroviral classes and combinations are discussed along with adverse effects, treatment failure, and their management.Published by
US Department of Health and Human Services
Published
2024
Summary
Provides recommendations regarding: prevention of exposure to, and diseases caused by, opportunistic infection pathogens. Discusses the importance of antiretroviral therapy in preventing and treating opportunistic infections. Also discusses primary prophylaxis (chemoprophylaxis and vaccination) and secondary prophylaxis (prevention of recurrence) and how to discontinue these once immune reconstitution has taken place. Also addresses issues relating to medication adverse effects and pregnancy.Published by
US Department of Health and Human Services
Published
2023
Summary
Evidence-based recommendations for the treatment of adult HIV infection with antiretroviral therapy.Published by
International Antiviral Society-USA
Published
2022
Summary
Practice advisory about the provision of antiretroviral pre-exposure prophylaxis.Published by
American College of Obstetricians and Gynecologists
Published
2022
Summary
Evidence-based information about the provision of antiretroviral pre-exposure prophylaxis.Published by
Centers for Disease Control and Prevention
Published
2021
Summary
Information on diagnosis and management of HIV and counseling of HIV-infected patients.Published by
Centers for Disease Control and Prevention
Published
2021
Summary
Evidence-based recommendations for the treatment of HIV infection.Published by
HIV Medicine Association of the Infectious Diseases Society of America
Published
2020
Summary
Chapter covers treatment and prevention of HIV infection.Published by
Centers for Disease Control and Prevention
Published
2023
Summary
This guideline provides a comprehensive overview of cardiovascular disease in people living with HIV.Published by
American Heart Association
Published
2019
Summary
Guidance for healthcare providers attending to the medical needs of adults and children with HIV who have been displaced from disaster areas and who have not yet secured HIV care in the areas where they have relocated.Published by
US Department of Health and Human Services
Published
2018
Summary
This guideline provides a comprehensive overview of the management of this condition.Published by
Infectious Diseases Society of America
Published
2017
Summary
This guideline provides a comprehensive overview of the management of this condition.Published by
CIHR Canadian HIV Trials Network
Published
2017
Summary
Compilation of new and longstanding recommendations that can help reduce the risk of HIV transmission from persons with HIV.Published by
Centers for Disease Control and Prevention
Published
2014
Summary
Recommends long-acting injectable cabotegravir may be offered as an additional HIV prevention option for people at substantial risk of HIV infection.Published by
World Health Organization
Published
2022
Summary
Provides an update on population levels of HIV drug resistance.Published by
World Health Organization
Published
2021
Summary
The World Health Organization brings together all existing guidance relevant to five key populations.Published by
World Health Organization
Published
2021
Summary
Evidence-based recommendations for the treatment of HIV infection with.Published by
World Health Organization
Published
2021
Summary
Recommendations concerning the use of hormonal contraceptive methods by women at high risk of HIV.Published by
World Health Organization
Published
2019
Summary
This guideline provides recommendations on antiretroviral regimens.Published by
World Health Organization
Published
2019
Summary
Guidelines that address the use of antiretroviral therapy for HIV treatment and prevention across all age groups and populations.Published by
World Health Organization
Published
2018
Summary
Provides recommendations for managing people presenting with advanced HIV disease.Published by
World Health Organization
Published
2017
Summary
Provides guidance on the public health response to pretreatment HIV drug resistance.Published by
World Health Organization
Published
2017
Summary
This guideline provides a comprehensive overview of the management of this condition.Published by
World Health Organization
Published
2016
Summary
This guideline provides a comprehensive overview of the management of this condition.Published by
World Health Organization
Published
2015
Summary
Provides recommendations on initiation of first-line antiretroviral therapy and second-line options in treatment failure. Includes guidance according to medication availability and resources in southern Africa. Also discusses treatment of HIV in patients with tuberculosis.Published by
Southern African HIV Clinicians Society
Published
2020
Summary
These evidence-based guidelines address clinical management of HIV-infected adults in Europe.Published by
European AIDS Clinical Society
Published
2022
Credits
Patient Instructions
- Good nutrition: wherever possible, a healthy balanced diet should be followed. Alcohol should be consumed only in moderation. A multivitamin that does not exceed the daily RDA value should be taken daily. Vitamin D supplementation should also be considered, although there is a lack of evidence to support this.[201]
- Lifestyle: safer sex advice is critical. Even in couples where HIV infection is concordant it is necessary to practice safer sex (use condoms) to prevent super-infection with a resistant virus. Cessation of smoking, alcohol abuse, and substance abuse are also important for a healthy lifestyle. Individuals who inject drugs should be offered harm reduction programs, including needle exchange and opioid dependence therapies.
- Reproduction: couples should be advised on their options for reproduction. This will differ depending on concordance and treatment. The estimated risk for male-to-female HIV transmission is 8 per 10,000 episodes of unprotected vaginal sex. No cases of HIV transmission have been reported in studies of serodiscordant couples in which the infected partner was virologically suppressed with antiretroviral therapy (ART); however, HIV RNA has been detected in the semen of men taking ART who have undetectable levels in their blood. Whether this poses a risk for transmission is unknown.[202] Advice at this stage should be that reproduction is possible and that it can be made as safe as possible, but that reproduction intention needs to be discussed with the practitioner well before conception to ensure best and safest possible scenarios for both partners and the potential infant. For serodiscordant couples, the Centers for Disease Control and Prevention recommends autologous sperm intrauterine insemination if the woman is HIV-positive, or one of the following options if the man is HIV-positive: use sperm from an HIV-negative donor (the safest option); use ART to suppress infection in the man and have condomless sex near ovulation while the woman is using pre-exposure prophylaxis; or collect and "wash" the sperm to remove HIV-infected cells in conjunction with ART and pre-exposure prophylaxis.[203]
- Natural history: patients generally need a sense of what to expect. The information should be based on what is known to be the natural history of HIV in most patients, with a discussion about rapid and long-term controllers but also recognition that most patients fall into the category of slow progressors. Drawing out the relationship between viral activity and CD4 count is a very useful graphic way for patients to better understand the relationship between viral activity and the progression of disease. The message should be tempered by the much more optimistic outlook in the ART era, and patients should be given the understanding that HIV is now a chronic and manageable infectious disease. The need for program adherence needs to be raised with an ultimate aim of drug adherence when the time comes. Some patients will benefit from comparing HIV to other chronic conditions that require regular monitoring (e.g., diabetes or asthma).
- Disclosure: it should be discussed that lifelong care and management will require support from other people in the patient's life. It should be explored who those people may be and how they may be engaged early on so that this support may be forthcoming. Patients sometimes appreciate help with disclosure, especially to sexual partners. A facilitator in this situation can quickly resolve any concerns and fears a sexual partner may have and also assist in further management of the contacts.
- Technology: mobile applications are available to assist with self-management of HIV.