Human Immunodeficiency Virus (HIV)

Transcription

1 Clinical Practice Guidelines Human Immunodeficiency Virus (HIV) OBJECTIVE The purpose is to guide the appropriate diagnosis and management of Human Immunodeficiency Virus (HIV). GUIDELINE These are only guidelines, and are based on the best available information at the time. These may not be all inclusive as new medications and treatments are ever-evolving. These guidelines are updated by MDwise at least biannually as national guidelines are updated. The practice care guidelines detailed in this document are consistent with the with the U.S. Preventive Services Task Force (USPSTF) and the Revised Recommendation for HIV testing of adults, Adolescents, and Pregnant Women in Health-Care Settings September22, 2006/55(RR14):1-17 National Guideline Clearinghouse (NGC) Guideline summary: Laboratory testing for the diagnosis of HIV infection: updated recommendations. AIDSinfo with the National Institute of Health: Guidelines for the use of Antiretroviral Agents in Adults and Adolescents Living with HIV Notice: Guidance for HIV treatment in adults is changing constantly with the advent of new therapies and other developments. You should frequently review the guidance on the for the latest recommendations. ASSESSMENT AND DIAGNOSIS Screening and Risk Assessment: It is recommended all adolescents and adults ages years should have HIV screening. Younger adolescents and adults over 65 who are at risk should also be screened. Repeat screening should be done for those persons at higher risk. Persons at very high risk should be screened at least annually. 1

2 Very high-risk factors include: o Men who have sex with men (MSM) o Active injection drug users Behavioral high-risk factors include: o Unprotected vaginal or anal intercourse o Multiple sexual partners or sex with someone who has multiple sexual partners o Unprotected mouth to-genital contact o Having sexual partners that are HIV-infected o Having sex with someone engaged in or has used injected drugs in the past o Engaging in anal sex or with someone else who has anal sex o Individuals who are bisexual o Exchanging sex for drugs or money o Individuals with new sexual partners o Other persons who have acquired or request testing for other sexually transmitted diseases (STD) o Individuals who live or receive medical care in a high-prevalence setting (defined as a geographic location or community with an HIV seroprevalance of at least 1%) All pregnant women must be screened for HIV as part a routine element of prenatal care A complete present and past medical history, physical examination, medication/social and family history, and a review of systems, including HIV-related information should be obtained for all patients upon initiation of care Routinely offering opt-out HIV testing to all persons at health facilities is recommended Community based testing is recommended to reach those who are less likely to attend a health facility Persons at risk for HIV are recommended to be proactively identified and managed for clinical mental health disorders (such as anxiety, depression and traumatic stress) and/or mental health issues related to HIV diagnosis, disclosure of status and/or HIV treatment Sharing of HIV testing and dispensing of Antiretroviral therapy and other appropriate tasks among professional and paraprofessionals healthcare workers is recommended including the use of lay health workers to enhance engagement of HIV care Screening Tests HIV diagnostic testing should begin with an FDA-approved HIV-1/2 Ag/Ab combination immunoassay also known as 4th-generation immunoassay (Exception: As of April 2016, data are insufficient to recommend use of the FDA-approved single-use rapid HIV-1/HIV-2 antigen/antibody combination immunoassay as the initial assay); No further testing is required for nonreactive specimens on the initial immunoassay Specimens with a reactive HIV-1/2 Ag/Ab combination immunoassay result are to then be tested using an HIV1/2 Ab differential immunoassay that has been FDA approved Specimens that are positive on the HIV-1/2 Ab differential immunoassay for HIV-1 Abs or HIV-2 Abs then proceed with medical evaluation for confirmed HIV-1 or HIV-2 infection Specimens that are positive antigen/antibody combination immunoassay and nonreactive or undetermined on the HIV-1/HIV-2 antibody differentiation immunoassay should be tested with the HIV-1 nucleic acid test (NAT) HIV-1 RNA test may be ordered as follow-up test after a positive antibody test or as part of a clinical workup Rapid testing may use either blood or oral fluid specimens. If any rapid HIV test is reactive (preliminary positive 2

3 result) the same algorithm noted above should be followed When diagnosis is made clinicians should discuss the importance of notifying all recent contacts and refer patients to partner notification services or offer HIV testing for partners. For high-risk individuals who test HIV negative, offering pre-exposure prophylaxis (PrEP) is recommended in addition to the provision of free condoms, education about risk reduction strategies, post-exposure prophylaxis (PEP), and voluntary medical male circumcision Screening Test Intervals One-time screening for adolescents and adults to identify persons who are already HIV-positive Persons at very high risk should be screened at least annually Repeat screening at least every three to five years for those known to be at risk for infection by actively engaging in risky behaviors Repeat screenings for those known to be in high-prevalence settings: o Geographic location or community with at least a 1% HIV seroprevalence o Sexually Transmitted Disease (STD) Clinics o Correctional facilities o Homeless shelters o Tuberculosis clinics o Clinics for MSM Other Testing to consider: A viral tropism testing should be performed if the use of a CCR5 antagonist is being considered or when virologic failure occurs when a patient is receiving a CCR5 antagonist Complete blood count and chemistry panel with differential white blood cell count should be obtained upon initiation of care Glucose-6-phosphate dehydrogenase screening is recommended upon entry into care or before starting therapy with an oxidant drug for patients with a predisposing racial or ethnic background Fasting lipid profile should be performed at the initiation of care HLA-B*5701 genotyping should be performed if abacavir therapy is to be initiated for abacavir naïve individuals Urinalysis and calculated creatine clearance or estimated glomerular filtration rate should be obtained due to increased risk of nephropathy in HIV positive patients. It should also be performed prior to initiating drugs such as tenofovir or indinavir that have the potential for neurotoxicity Coinfection and Comorbidity Lab Testing: Chronic viral hepatitis B (HBV) Hepatitis C (HCV) Tuberculosis Toxoplasma gondii Viral Hepatitis Herpes Virus Syphilis 3

4 Chlamydia Gonorrhea Trichomoniasis Stages of HIV 1. Acute HIV Infection: is the earliest stage of HIV infection, and it usually develops between 2 4 weeks after a person is infected. Symptoms may include: Flu like symptoms Fever Headache Rash During this stage the level of HIV in the blood is very high and generally increases the risk of HIV transmission. 2. Chronic HIV Infection: It is also called asymptomatic HIV or clinical latency. It is during this stage that HIV continues to multiply in the body at very low levels and may not have HIV related symptoms, but it can still be transmitted to others. Lacking treatment with antiretroviral therapy (ART) it usually advances to AIDS in 10 or more years, although in some people it may take less time to progress. 3. AIDS: Is the final stage and the most severe stage of HIV due to increasingly compromised immune system, resulting in the immune system making it hard for the body to fight opportunistic infections. For those diagnosed with AIDS, if their CD4 count is < 200 cells/mm3 or if certain other opportunistic infections are present, without treatment they usually survive about 3 years. TREATMENT Without antiretroviral therapy (ART), most patients will eventually develop AIDS. The primary goal is to prevent AIDS defining morbidities and premature mortality. This is best achieved by using ART to maximally inhibit HIV replication to sustain a plasma viral load lower than the quantification by available assays. Recommendations for ART for all individuals, regardless of CD4 cell count, is to reduce morbidity and mortality. ART is also recommended as preventive treatments for those individuals with HIV to prevent HIV transmissions. When initiating therapy, it is critical to educate on the benefits of ART, and to address the barriers to adherence and offer care plan strategies to optimize adherence. On an individual basis, ART may be deferred because of clinical or psychosocial factors, but treatments should be started as soon as possible. Please advise patients that current ART does not cure HIV, however it is also recommended in individuals with HIV to prevent HIV transmission. Although ART is recommended in all patients there are certain conditions that increase the urgent need to begin ART therapy these include: Pregnancy HIV/Hepatitis B coninfection HIV/Hepatitis C coninfection Acute/early infection Lower CD4 counts 4

5 HIV-associated neuropathy Acute opportunistic infections AIDS defining comorbidities, such as HIV associated dementia and AIDS assossicated malignancies Treatment for naive patients generally consists of two nucleoside reverse transcriptase inhibitors (NRTIs) in combination with a third active drug from one of three drug class: an integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor (PI) with a pharmacokinetic (PK) enhancer (booster) (cobicistat or ritonavir). The panel on Antiretroviral Guidelines for Adults and Adolescents classified the regimens as Recommended Initial Regimens for most people with HIV (in alphabetical order): Dolutegravir/abacavir/lamivudine only for those who are HLA-B*5701 negative * Dolutegravir plus tenofovir/emtricitabine * Elvitegravir/cobicistat/tenofovir/emtricitabine * A recently published safety announcement from the FDA is alerting the public that serious cases of neural tube birth defects involving the brain, spin, and spinal cord have been reported in babies born to women treated with dolutegravir. The FDA is currently reviewing this safety issue and will update the public when they have further information. Health care professionals should inform women of childbearing age about the potential risk of neural tube defects when a dolutegravir- containing regimen is used at the time of conception and early in pregnancy. Community based ART distribution is recommended and systematic monitoring of retention of HIV care is recommended to increase retention in care, ART adherence and viral suppression in all patients. This includes routine collection of self-reported adherence data from all patients. Pharmacy refill data are also recommended for adherence monitoring. Mobile health technology using weekly interactive components such as 2-way text messaging is also recommended along with using alarm devices as reminders. Patient education about and offering support for medication adherence and keeping clinical appointments is recommended as well. Directly administered ART is recommended for people who inject drugs and released prisioners at high risk of ART non-adherence. Proactive engagement and reengangement of people living with HIV who miss clinic appointments and/or are lost to follow-up is recommended, including outreach to those not engaged in care within 1 month of a new diagnosis. When assessing and managing a patient with failing ART it is critical that expert advise should be sought. When assessing patients with failing treatment it is important that drug-resistant testing be completed either preferably while the patient is still taking the failing medications or within 4 weeks of treatment discontinuation. It is not recommended to add a single agent to a virologically failing regimen due to the fact that this may risk the development of resistance to all the drugs in the regimen. Discontinuing or briefly interrupting therapy may lead to a greater increase in HIV RNA, a decrease in the CD4 cell count, and an increase in the risk of clinical progression. Therefore, this is not recommended in patients with virologic failure. 5

6 In pregnant women, one additional goal is to maintain a viral load below the limit of detection during the full pregnancy to reduce the risk of transmission to the fetus and newborn child. While treating pregnant women it is important to consider safety, efficacy, and pharmacokinetic data on use during pregnancy for each drug and should be discussed with all women. All non-pregnant women of childbearing age should undergo pregnancy testing before the initiation of certain medications and offered counseling on contraception while on these medications. In cases with Heptitis B and HIV coinfection, it is not recommended to use interferon-free HCV treatment. All patients initiating HCV therapy should be tested for HBV. All persons that are HCV/HIV positive and have an active HBV infection should receive ART that includes two agents with Anti HBV activity prior to initiating HCV treament. 6

7 Class Agent(s) Advantage(s) DualNRTI ABC/DTG/3TC abacavir sulfate / dolutegravir (Triumeq) / and lamivudine Co-formulated with DTG TAF/FTC emtricitabine / tenofovir alafenamide fumarate Co-formulated with EVG/c or RPV Active against HBV; a recommended dual-nrti option for patients with HIV/HBV coinfection Smaller decline in renal function, less proteinuria, and smaller reductions in BMD than after initiation of TDF/FTC Approved for patients with egfr 30 ml/min Co-formulated with EFV, EVG/c, and RPV as STRs Active against HBV; a recommended dual- NRTI option for patients with HIV/HBV coinfection Better virologic responses than with ABC/3TC in patients with baseline viral load 100,000 copies/ml when combined with ATV/r or EFV Associated with lower lipid levels than ABC or TAF TDF/FTC tenofovir disoproxil fumarate / emtricitabine 7 Disadvantage(s) May cause life-threatening HSRs in patients positive for the HLAB*5701 allele. As a result, HLA-B*5701 testing is required before use. If positive, patients should have this added to their Allergy list with all healthcare providers. In the ACTG 5202 study, patients with baseline HIV RNA 100,000 copies/ml showed inferior virologic responses when ABC/3TC was given with EFV or ATV/r as opposed to TDF/FTC. This difference was not seen when ABC/3TC was used in combination with DTG. ABC use has been associated with CV disease and cardiac events in some, but not all, observational studies. A recently published safety announcement from the FDA is alerting the public that serious cases of neural tube birth defects involving the brain, spin, and spinal cord have been reported in babies born to women treated with dolutegravir. The FDA is currently reviewing this safety issue and will update the public when they have further information. TDF is associated with lower lipid levels than TAF, perhaps because TDF results in higher plasma levels of tenofovir, which lowers lipids. Renal toxicity, including proximal tubulopathy and acute or chronic renal insufficiency Osteomalacia has been reported as a consequence of proximal tubulopathy. Decreases BMD more than other NRTI combinations

8 Class INSTI 8 Agent(s) Advantage(s) Disadvantage(s) DTG dolutegravir (Triumeq) Higher barrier to resistance than EVG or RAL Co-formulated with ABC and 3TC No food requirement No CYP3A4 interactions Favorable lipid profile EVG/c elvitegravir/ cobicistat Co-formulated with TDF/FTC or TAF/FTC Compared with ATV/r, causes smaller increases in total and LDL cholesterol Oral absorption of DTG can be reduced by simultaneous administration with drugs containing polyvalent cations (e.g., Al, Ca, or Mg-containing antacids or supplements, or multivitamin tablets with minerals). Inhibits renal tubular secretion of Cr and can increase serum Cr without affecting glomerular function UGT substrate; potential for drug interactions Depression and suicidal ideation (rare; usually in patients with preexisting psychiatric conditions) A recently published safety announcement from the FDA is alerting the public that serious cases of neural tube birth defects involving the brain, spin, and spinal cord have been reported in babies born to women treated with dolutegravir. The FDA is currently reviewing this safety issue and will update the public when they have further information. EVG/c/TDF/FTC is only recommended for patients with baseline CrCl 70 ml/min; this regimen should be discontinued if CrCl decreases to <50 ml/min. COBI is a potent CYP3A4 inhibitor, which can result in significant interactions with CYP3A substrates. Oral absorption of EVG can be reduced by simultaneous administration with drugs containing polyvalent cations (e.g., Al, Ca, or Mg-containing antacids or supplements, or multivitamin tablets with minerals). COBI inhibits active tubular secretion of Cr and can increase serum Cr, without affecting renal glomerular function. Lower genetic barrier to resistance than boosted PI- or DTG-based regimens Food requirement Depression and suicidal ideation (rare; usually in patients with preexisting psychiatric conditions) RAL raltegravir Compared to other INSTIs, has longest post- marketing experience No food requirement No CYP3A4 interactions Favorable lipid profile Lower genetic barrier to resistance than boosted PI- or DTG-based regimens Increases in creatine kinase, myopathy, and rhabdomyolysis have been reported. Rare cases of severe HSRs (including SJS and TEN) have been reported. Higher pill burden than other INSTI-based regimens No fixed-dose combination formulation Oral absorption of RAL can be reduced by simultaneous administration with drugs containing polyvalent cations (e.g., Al, Ca, or Mg-containing antacids or supplements, or multivitamin tablets with minerals). UGT substrate; potential for drug interactions Depression and suicidal ideation (rare; usually in patients with preexisting psychiatric conditions)

9 Class Agent(s) INSTI, continued NNRTIs 9 Advantage(s) Disadvantage(s) BIC Bictegravir /TAF Tenofovir/ Alafenamibe/ FTC Emtricitabine Co-formulated with TAF/FTC BIC/TAF/FTC is an effective and well-tolerated INSTI-based regimen for initial therapy in adults with HIV, with efficacy that is non-inferior to DTG/ABC/3TC and DTG plus TAF/FTC for up to 48 weeks. Is recommended as an initial regimen for most adults BIC/TAF/FTC is not recommended in patients with a creatinine clearance < 30 ml/min or with severe liver impairment Is not FDA approved for patients younger than age 18 There is not enough safety information regarding its use in pregnancy Common side effects were nausea, diarrhea, and headache Oral absorption of BIC can be reduced by simultaneous administration with drugs containing polyvalent cations (e.g., Al, Ca, or Mg-containing antacids or supplements, or iron supplements). BIC is an inhibitor of the drug transporters OAT2 and MATE1, which may lead to increased concentrations of drugs that are substrates of these transporters. For this reason, dofetilide is contraindicated with BIC/TAF/FTC. BIC is a cytochrome P (CYP) 3A4 and a uridine diphosphate glucuronosyltransferase (UGT) 1A1 substrate, and its metabolism may be affected by concomitant use of a CYP3A4 and UGT1A1 inducer or inhibitor. Rifampin or other rifamycins may decrease BIC or TAF concentrations, which may result in loss of therapeutic effect. BIC/FTC/TAF should not be used in patients who require rifamycins. Certain anticonvulsants and St. John s Wort should also be avoided. EFV efavirenz Co-formulated with TDF/FTC Long-term clinical experience EFV-based regimens (except for EFV + ABC/3TC) have welldocumented efficacy in patients with high HIV RNA. Short-and long-term neuropsychiatric (CNS) side effects, including depression and, in some studies, suicidality Teratogenic in nonhuman primates Dyslipidemia Rash QTc interval prolongation; consider an alternative to EFV in patients taking medications with known risk of causing TdP, or in those at higher risk of TdP Transmitted resistance more common than with PIs and INSTIs Greater risk of resistance at the time of treatment failure than with PIs Potential for CYP450 drug interactions Should be taken on an empty stomach (food increases drug absorption and CNS toxicities)

10 Class Agent(s) Advantage(s) Disadvantage(s) NNRTIs continued RPV rilpivirine Co-formulated with TDF/FTC and TAF/FTC RPV/TDF/FTC and RPV/TAF/FTC have smaller pill size than other co-formulated drugs Compared with EFV: Fewer CNS adverse effects Fewer lipid effects Fewer rashes Not recommended in patients with pre-art HIV RNA >100,000 copies/ml or CD4 count <200 cells/mm3 because of higher rate of virologic failure in these patients Depression and suicidality QTc interval prolongation; consider an alternative to RPV in patients taking medications with known risk of causing TdP, or in those at higher risk of TdP Rash Transmitted resistance more common than with PIs and INSTIs More NNRTI-, TDF-, and 3TC-associated mutations at virologic failure than with regimen containing EFV and 2 NRTIs Potential for CYP450 drug interactions Meal requirement (>390 kcal) Requires acid for adequate absorption Contraindicated with PPIs Use with H2 antagonists or antacids with caution for detailed dosing information PIs protease inhibitor ATV/c atazanavir / cobicistat Higher genetic barrier to resistance than NNRTIs, EVG, and RAL PI resistance at the time of treatment failure uncommon with PK-enhanced PIs ATV/c and ATV/r have similar virologic activity and toxicity profiles Observational cohort studies have found an association between some PIs (DRV, LPV/r, FPV, IDV) and an increased risk of CV events, while this has not been seen with ATV. Further study is needed. See text for discussion. Co-formulated tablet Commonly causes indirect hyperbilirubinemia, which may manifest as scleral icterus or jaundice Food requirement Absorption depends on food and low gastric ph for interactions with H2 antagonists, antacids, and PPIs Nephrolithiasis, cholelithiasis, nephrotoxicity GI adverse effects CYP3A4 inhibitors and substrates: potential for drug interactions or ATV/r atazanavir / ritonavir ATV/c (Specific considerations) DRV/c darunavir / cobicistat; or DRV/r darunavir / ritonavir 10 Higher genetic barrier to resistance than NNRTIs, EVG, and RAL PI resistance at the time of treatment failure uncommon with PK-enhanced PIs COBI inhibits active tubular secretion of Cr and can increase serum Cr, without affecting renal glomerular function. Co-administration with TDF is not recommended in patients with CrCl <70 ml/min Less long-term clinical experience than for ATV/r COBI (like RTV) is a potent CYP3A4 inhibitor, which can result in significant interactions with CYP3A substrates. Skin rash Food requirement GI adverse effects CYP3A4 inhibitors and substrates: potential for drug interactions Increased CV risk in one observational cohort study

11 Class Agent(s) Advantage(s) PIs, continued DRV/c (Specific considerations) Co-formulated tablet Less long-term clinical experience than for DRV/r COBI inhibits active tubular secretion of Cr and can increase serum Cr, without affecting renal glomerular function. Co-administration with TDF is not recommended in patients with CrCl <70 ml/min Approval primarily based on PK data comparable to that for DRV/r rather than on trials comparing the efficacy of DRV/c and DRV/r COBI (like RTV) is a potent CYP3A4 inhibitor, which can result in significant interactions with CYP3A substrates. LPV/r lopinavir / ritonavir Only RTV-co-formulated PI No food requirement Requires 200 mg per day of RTV Possible higher risk of MI associated with cumulative use of LPV/r PR and QT interval prolongation have been reported. Use with caution in patients at risk of cardiac conduction abnormalities or in patients receiving other drugs with similar effect. Possible nephrotoxicity CYP3A4 inhibitors and substrates: potential for drug Ibalizumab (Trogarzo) Dose modifications are not required when administered with another antiretroviral No contraindications noted Benefit of this medication is achieving reduction of the HIV RNA. Administered intravenously as a single loading dose of 2,000 mg followed by a maintenance dose of 800 mg every 2 weeks Once loading dose is complete observe patient for 1 hour for infusion associated adverse reactions. If no adverse reaction noted post-infusion observation can be decreased to 15 min. If a maintenance dose is missed by 3 days or longer beyond the scheduled dosing day a loading dose (2,000 mg) should be administered as early as possible. then resume maintenance dose of (800 mg) every 14 days Severe adverse reaction noted was Immune Reconstitution Inflammatory Syndrome in only 1 patient. Common adverse reactions in at least 5% were diarrhea, dizziness, nausea, and rash Postattachment Inhibitors block the CD4 receptors on the surface of certain immune cells that HIV needs to enter the cells. Disadvantage(s) Key to Acronyms: 3TC = lamivudine; ABC = abacavir; Al = aluminum; ART = antiretroviral therapy; = antiretroviral; ATV = atazanavir; BMD = bone mineral density; Ca = calcium; CD4 = CD4 T lymphocyte; CNS = central nervous system; COBI or c = cobicistat; Cr = creatinine; CrCl = creatinine clearance; CV = cardiovascular; CYP = cytochrome P; DRV = darunavir; DTG = dolutegravir; egfr = estimated glomerular filtration rate; EFV = efavirenz; EVG = elvitegravir; FPV = fosamprenavir; FTC = emtricitabine; GI = gastrointestinal; HBV = hepatitis B virus; HLA = human leukocyte antigen; HSR = hypersensitivity reaction; IDV = indinavir; INSTI = integrase strand transfer inhibitor; LDL = low-density lipoprotein; LPV = lopinavir; Mg = magnesium; MI = myocardial infarction; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PK = pharmacokinetic; PPI = proton pump inhibitor; RAL = raltegravir; RPV = rilpivirine; RTV or r = ritonavir; SJS = StevensJohnson syndrome; STR = single-tablet regimen; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TdP = torsades de pointes; TEN = toxic epidermal necrosis; UGT = uridine diphosphate glucuronosyltransferase For more information on drug interactions please refer to the link noted below 11

12 REFERENCES Accessed 2/27/2018 Judith A. Aberg, Joel E. Gallant, Khalil G. Ghanem, Patricia Emmanuel, Barry S. Zingman, Michael A. Horberg; Primary Care Guidelines for the Management of Persons Infected With HIV: 2013 Update by the HIV Medicine Association of the Infectious Diseases Society of America. Accessed January 25, Accessed 2/27/18 National Guideline Clearinghouse (NGC). Guideline summary: Laboratory testing for the diagnosis of HIV infection: updated recommendations. In: National Guideline Clearinghouse (NGC) [Web site]. Rockville (MD): Agency for Healthcare Research and Quality (AHRQ); 2014 Jun 27. [cited 2017 Mar 02]. Available: National Guideline Clearinghouse (NGC). IAPAC Guideline for optimizing the HIV care continuum for adults and adolescents. In: National Guideline Clearinghouse (NGC) [Web site]. Rockville (MD): Agency for Healthcare Research and Quality (AHRQ) 2015 Nov-Dec; Available: Indiana Family and Social Services Administration Indiana Health Coverage Programs, Provider Reference Module, Laboratory Services, Library Reference Number: PROMOD ; Published: October 27, 2016; Policies and procedures as of April 1, 2016; Version: 1.1 Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV Downloaded from Downloaded 3/21/2018 Centers for Disease Control and Prevention, Health Resources and Services Administration, National Institutes of Health, American Academy of HIV Medicine, Association of Nurses in AIDS Care, International Association of Providers of AIDS Care, the National Minority AIDS Council, and Urban Coalition for HIV/AIDS Prevention Services. Recommendations for HIV Prevention with Adults and Adolescents with HIV in the United States, FDA Drug Safety Communication: FDA to evaluate potential risk of neural tube birth defects with HIV medicine dolutegravir (Juluca, Tivicay, Triumeq) Published 5/18/18. Last accessed 5/23/18. MDwise Medical Advisory Council -- Approval Date 5/2/18 HHW-HIPP0563(5/18) 12