Use of Antiretroviral Agents in Adults and Adolescents with HIV

For Antiretroviral Therapy-Naive Persons:
• HIV drug-resistance testing is recommended at entry into care for persons with HIV to guide selection of the initial antiretroviral therapy (ART) regimen (AII). If therapy is deferred, repeat testing may be considered at the time of ART initiation (CIII).

• Genotypic, rather than phenotypic, testing is the preferred resistance testing to guide therapy in antiretroviral (ARV)-naive patients (AIII).

• In persons with acute or recent (early) HIV infection, in pregnant people with HIV, or in people who will initiate ART on the day of or soon after HIV diagnosis, ART initiation should not be delayed while awaiting resistance testing results; the regimen can be modified once results are reported (AIII).

• Standard genotypic drug-resistance testing in ARV-naive persons involves testing for mutations in the reverse transcriptase (RT) and protease (PR) genes. If transmitted integrase strand transfer inhibitor (INSTI) resistance is a concern, providers should ensure that genotypic resistance testing also includes the integrase gene (AIII).


For Antiretroviral Therapy-Experienced Persons:
• HIV drug-resistance testing should be performed to assist the selection of active drugs when changing ART regimens in the following patients:
• Persons with virologic failure and HIV RNA levels >1,000 copies/mL (AI)
• Persons with HIV RNA levels >500 copies/mL but <1,000 copies/mL, drug-resistance testing may be unsuccessful but should still be considered (BII)
• Persons with suboptimal viral load reduction (AII)

• When a person with HIV experiences virologic failure while receiving an INSTI-based regimen, genotypic testing for INSTI resistance (which may need to be ordered separately) should be performed to determine whether to include a drug from this class in subsequent regimens (AII).

• Drug-resistance testing in the setting of virologic failure should be performed while the person is taking prescribed ARV drugs or, if that is not possible, within 4 weeks after discontinuing therapy (AII). If more than 4 weeks have elapsed since the ARVs were discontinued, resistance testing may still provide useful information to guide therapy; however, it is important to recognize that previously selected resistance mutations can be missed due to lack of drug-selective pressure (CIII).

• Genotypic testing is preferred over phenotypic resistance testing to guide therapy in persons with suboptimal virologic response or virologic failure while on first- or second-line regimens and in individuals in whom resistance mutation patterns are known or not expected to be complex (AII).

• The addition of phenotypic to genotypic resistance testing is recommended for persons with known or suspected complex drug-resistance mutation patterns (BIII).

• All prior and current drug-resistance test results, if available, should be considered when constructing a new regimen for a patient (AIII).

• A co-receptor tropism assay should be performed whenever the use of a CCR5 co-receptor antagonist is being considered (AI).

• Co-receptor tropism testing is recommended for patients who exhibit virologic failure on a CCR5 antagonist (BIII).

• A phenotypic tropism assay is preferred to determine HIV-1 co-receptor usage (AI).

• A genotypic tropism assay should be considered as an alternative test to predict HIV-1 co-receptor usage (BII).

• A proviral DNA tropism assay can be utilized for patients with undetectable HIV-1 RNA when a CCR5 antagonist is considered for use in a new regimen (e.g., as part of a regimen switch or simplification) (BII).

• The Panel recommends screening for HLA-B*5701 before starting patients on an abacavir (ABC)-containing regimen to reduce the risk of hypersensitivity reaction (HSR) (AI).

• HLA-B*5701-positive patients should not be prescribed ABC (AI).

• The positive status should be recorded as an ABC allergy in the patient’s medical record (AII).

• When HLA-B*5701 screening is not readily available, it remains reasonable to initiate ABC with appropriate clinical counseling and monitoring for any signs of HSR (CIII).

• Antiretroviral therapy (ART) is recommended for all persons with HIV to reduce morbidity and mortality (AI) and to prevent the transmission of HIV to others (AI).

• The Panel on Antiretroviral Guidelines for Adults and Adolescents recommends initiating ART immediately (or 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 for individual patients, and improve the rate of virologic suppression among persons with HIV (AII).

• When initiating ART, it is important to educate patients regarding the benefits of ART and to deploy strategies to optimize care engagement and treatment adherence (AIII).

• All persons with HIV should be informed that maintaining a plasma HIV RNA (viral load) of <200 copies/mL, including any measurable value below this threshold value, with antiretroviral therapy (ART) prevents sexual transmission of HIV to their partners. Patients may recognize this concept as Undetectable = Untransmittable or U=U (AII).

• Persons with HIV who are starting ART should use another form of prevention with sexual partners (e.g., condoms, pre-exposure prophylaxis [PrEP] for the HIV-negative sexual partner, sexual abstinence) for at least the first 6 months of treatment and until a viral load of <200 copies/mL has been documented (AII). Many experts would recommend confirming sustained suppression before assuming that there is no further risk of sexual HIV transmission (AIII).

• When the viral load is ≥200 copies/mL, additional methods are needed to prevent transmission of HIV to sexual partners until resuppression to <200 copies/mL has been confirmed (AIII).

• Persons with HIV who intend to rely upon ART for prevention need to maintain high levels of ART adherence (AIII). They should be informed that transmission is possible during periods of poor adherence or treatment interruption (AIII).

• At each visit for HIV care, clinicians should assess adherence to ART and counsel patients regarding the importance of ART to their own health as well as its role in preventing sexual HIV transmission (AIII).

• Providers should inform patients that maintaining a viral load of <200 copies/mL does not prevent acquisition or transmission of other sexually transmitted infections (STIs) (AII).

• Providers should also routinely screen all sexually active persons with HIV for STIs, both for their own health and to prevent transmission of STIs to others (AIII).

• An antiretroviral (ARV) regimen for a treatment-naive patient generally consists of two nucleoside reverse transcriptase inhibitors (NRTIs) administered in combination with a third active ARV drug from one of three drug classes: an integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor (PI) with a pharmacokinetic (PK) enhancer (also known as a booster; the two drugs used for this purpose are cobicistat and ritonavir).

• Data also support the use of the two-drug regimen, dolutegravir plus lamivudine, for initial treatment.

• Before initiating antiretroviral therapy (ART) in a person of childbearing potential, clinicians should discuss the person’s intentions regarding pregnancy and a pregnancy test should be performed (AIII). Clinicians should refer to the Perinatal Guidelines for recommendations on initial ARV regimen for an ART-naive person around the time of conception and during pregnancy.

• The Panel on Antiretroviral Guidelines for Adults and Adolescents (the Panel) classifies the following regimens as Recommended Initial Regimens for Most People with HIV (in alphabetical order):
• Bictegravir/tenofovir alafenamide/emtricitabine (AI)a
• Dolutegravir/abacavir/lamivudine—only for individuals who are HLA-B*5701 negative and without chronic hepatitis B virus (HBV) coinfection (AI)
• Dolutegravir plus (emtricitabine or lamivudine) plus (tenofovir alafenamide [TAF] or tenofovir disoproxil fumarate [TDF])b (AI)
• Dolutegravir/lamivudine (AI)—except for individuals with HIV RNA >500,000 copies/mL, HBV coinfection, or when ART is to be started before the results of HIV genotypic resistance testing for reverse transcriptase or HBV testing are available.

• To address individual patient characteristics and needs, the Panel also provides a list of Recommended Initial Regimens in Certain Clinical Situations (see Table 6 below).

• Given the many excellent options for initial therapy, selection of a regimen for a particular patient should be guided by such factors as virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance test results, comorbid conditions, access, and cost. Table 7 provides guidance on choosing an ARV regimen based on selected clinical case scenarios. Table 9 highlights the advantages and disadvantages of different components in a regimen.

• Patients without prior ART who wish to begin long-acting intramuscular cabotegravir (CAB) and rilpivirine (RPV) should first achieve viral suppression on another regimen before switching to oral, and then injectable, CAB and RPV (see Optimizing Antiretroviral Therapy in the Setting of Virologic Suppression).

• Assessing and managing a patient who is experiencing antiretroviral therapy (ART) failure can be complex. Expert advice can be critical and should be sought in many instances.

• Evaluation of virologic failure should include an assessment of adherence, drug-drug and drug-food interactions, drug tolerability, HIV RNA level and CD4 T lymphocyte (CD4) cell count trends over time, ART history, and prior and current drug-resistance test results.

• Drug-resistance testing should be performed while the patient is taking the failing antiretroviral (ARV) regimen (AI) or within 4 weeks of treatment discontinuation (AII). If more than 4 weeks have elapsed since ARV drugs were discontinued, resistance testing can still provide useful information to guide therapy, although it may not detect previously selected resistance mutations (CIII).

• The goal of treatment for ART-experienced patients with drug resistance who are experiencing virologic failure is to establish suppression (i.e., HIV RNA levels below the lower limits of detection of currently used assays) (AI).

• A new regimen can include two fully active ARV drugs if at least one with a high resistance barrier is included (e.g., dolutegravir or boosted darunavir) (AI). If no fully active drug with a high resistance barrier is available, then every effort should be made to include three fully active drugs (AI).

• In general, adding a single ARV agent to a virologically failing regimen is not recommended, because this would rarely result in full viral suppression and, therefore, may risk the development of resistance to all drugs in the regimen (BII).

• For some highly ART-experienced patients with extensive drug resistance, maximal virologic suppression may not be possible. In this case, ART should be continued (AI) with regimens that are designed to minimize toxicity, preserve CD4 counts, and delay clinical progression.

• When it is not possible to construct a viable suppressive regimen for a patient with multidrug-resistant HIV, the clinician should consider enrolling the patient in a clinical trial of investigational agents or contacting pharmaceutical companies that may have investigational agents available.

• In patients with virologic failure, it is crucial to provide continuous adherence support before and after ARV regimen changes.

• When switching an ARV regimen in a patient with hepatitis B virus (HBV)/HIV coinfection, ARV drugs that are active against HBV should be continued as part of the new regimen. Discontinuation of these drugs may lead to the reactivation of HBV, which may result in serious hepatocellular damage.

• Discontinuing or briefly interrupting therapy may lead to a rapid increase in HIV RNA, a decrease in CD4 count, and an increase in the risk of clinical progression. Therefore, this strategy is not recommended in the setting of virologic failure (AI).

• Persistently low CD4 T lymphocyte (CD4) cell counts and immune activation are each associated with increased AIDS- and non-AIDS-related morbidity and mortality among individuals with antiretroviral therapy (ART)-mediated viral suppression.

• Adding antiretroviral (ARV) drugs to a suppressive ARV regimen (ART intensification) does not improve CD4 cell recovery or reduce immune activation and, therefore, is not recommended (AI).

• In individuals with viral suppression, switching ARV drug classes does not consistently improve CD4 cell recovery or reduce all relevant markers of immune activation and is not recommended (BIII).

• Interleukin-2 is not recommended (AI) to increase CD4 cell counts and/or decrease immune activation, because clinical trial data demonstrated no clinical benefit.

• Other interventions designed to increase CD4 cell counts and/or decrease immune activation are not recommended outside of a clinical trial, because no current interventions have been proven to decrease morbidity or mortality during ART-mediated viral suppression (AII).

• Efforts to decrease morbidity and mortality during ART-mediated viral suppression should focus on addressing modifiable risk factors for chronic disease (e.g., encouraging smoking cessation, a healthy diet, and regular exercise; treating hypertension and hyperlipidemia).

• Monitoring markers of immune activation and inflammation is not recommended, because no intervention targeting immune pathways has proven to improve the health of individuals with HIV, and many blood markers that predict morbidity and mortality fluctuate within individuals (AII).

• Advances in antiretroviral (ARV) treatment and a better understanding of HIV drug resistance have made itpossible to consider switching a person with HIV from an effective regimen to an alternative regimen in somesituations.

• The fundamental principle of regimen optimization is to maintain viral suppression without jeopardizing futuretreatment options.

• Adverse events, drug-drug or drug-food interactions, pill burden, pregnancy, cost, or the desire to simplify aregimen may prompt a regimen switch.

• It is critical to review a patient’s full ARV history, including virologic responses, past ARV-associated toxicities andintolerances, and cumulative resistance test results before selecting a new ARV regimen (AI).

• A long-acting ARV regimen, such as the combination of injectable cabotegravir and rilpivirine, is an optimizationoption for patients who are engaged with their health care, virologically suppressed on oral therapy for 3 to 6months, and who agree to make the frequent clinic visits needed to receive the injectable drugs (AI).

• Monotherapy with either a boosted protease inhibitor or an integrase strand transfer inhibitor has been associatedwith unacceptable rates of virologic failure and the development of resistance; therefore, monotherapy as aswitch strategy is not recommended (AI).

• When switching an ARV regimen in a person with hepatitis B virus (HBV)/HIV coinfection, ARV drugs thatare active against HBV should be continued (AII). Using lamivudine or emtricitabine as the only drug in aregimen with HBV activity is not recommended (AII), because HBV resistance to these drugs can emerge.Discontinuation of HBV drugs may lead to reactivation of HBV, which may result in serious hepatocellulardamage.

• Consultation with an HIV specialist is recommended when planning a regimen switch for a patient with a historyof resistance to one or more drug classes (AIII).

• Close monitoring to assess tolerability, viral suppression, adherence, and safety is recommended during the first3 months after a regimen switch (AIII).

•Antiretroviral therapy (ART) is recommended for all persons with HIV, including those with earlya HIV infection (AI). ARTshould be initiated as soon as possible after HIV diagnosis (AII).

•The goals of ART are to suppress plasma HIV RNA to undetectable levels (AI) and to prevent transmission of HIV (AI).Monitoring of plasma HIV RNA levels, CD4+ T lymphocyte counts, and antiretroviral (ARV) drug-related adverse effectsshould be done as recommended for persons with chronic HIV infection (AII).

•A blood sample for genotypic testing should be sent to the laboratory before initiation of ART (AIII). ART can be initiatedbefore drug-resistance test and HLA B*5701 test results are available. In this setting, one of the following ARV regimens isrecommended (AIII):
oBictegravir (BIC)/tenofovir alafenamide (TAF)/emtricitabine (FTC)
oDolutegravir (DTG) with (TAF or tenofovir disoproxil fumarate [TDF])b plus (FTC or lamivudine [3TC])
oBoosted darunavir (DRV) with (TAF or TDF)b plus (FTC or 3TC)

•Pregnancy testing should be performed in persons of childbearing potential before initiation of ART (AIII). See text belowregarding data on the use of BIC and DTG in persons of childbearing potential.

•When the results of drug-resistance and HLA-B*5701 tests are available, the treatment regimen can be modified if needed (AII).

•Providers should inform individuals starting ART of the importance of adherence to achieve and maintain viral suppression (AIII).

• Adolescents and young adults (AYA) with HIV largely belong to two distinct groups: those who acquired HIV inthe first decade of life and who may be heavily antiretroviral therapy (ART)–experienced (early-acquired HIV);and those who acquired HIV in or after the second decade of life who may be mostly ART-naive.

• ART is recommended for all AYA with HIV (AI) to reduce HIV-related morbidity, mortality, and transmission.

• For AYA with HIV who are at risk for poor clinical outcomes, it is critically important to assess the behavioral andpsychosocial context, and their ability to adhere to ART. Efforts should be made to provide youth-friendly supportand infrastructure to reduce barriers to adherence and maximize success in achieving sustained viral suppression (AIII).

• Pediatric and adolescent care providers should prepare AYA with HIV for the transition into adult care settings.Adult providers should be knowledgeable about this unique patient population and the challenges that frequentlyaccompany the transition into the adult care setting. Consulting and collaborating with pediatric and adolescentHIV care providers is critical to ensure the successful transition of AYA with HIV to adult providers and continuedengagement in care (AIII).

• The clinical course of HIV-2 infection is generally characterized by a longer asymptomatic stage, lower plasma viral loads, and lowermortality rate than HIV-1 infection. However, progression to AIDS and death will occur in the majority of individuals without treatment.

• No randomized controlled trials have addressed when a person with HIV-2 should start antiretroviral therapy (ART) or whichregimens are most effective for initial or second-line ART when treating HIV-2; thus, the optimal treatment strategy is not well defined.

• Existing data on the treatment of HIV-2, and extrapolation from data on the treatment of HIV-1, suggest that ART should be started ator soon after HIV-2 diagnosis to prevent disease progression and transmission of HIV-2 to others (AIII).

• Quantitative plasma HIV-2 RNA viral load testing for clinical care is available and should be performed before initiation of ART (AIII).

• HIV-2 is intrinsically resistant to non-nucleoside reverse transcriptase inhibitors and to enfuvirtide; therefore, these drugs should notbe included in ART regimens for HIV-2 infection (AII).

• Patients with hepatitis B virus (HBV)/HIV-2 coinfection should be prescribed ART regimens that contain drugs with activity againstboth HIV-2 and HBV (AIII).

• Initial ART regimens for ART-naive patients who have HIV-2 mono-infection or HIV-1/HIV-2 coinfection should include an integrasestrand transfer inhibitor (INSTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs) (AII). An alternative regimen is aboosted protease inhibitor (PI) that is active against HIV-2 (darunavir or lopinavir) plus two NRTIs (BII).

• HIV-2 RNA, CD4 T lymphocyte (CD4) cell counts, and clinical status should be used to assess treatment response (AIII).Unlike persons with HIV-1, persons with HIV-2 should continue to undergo periodic CD4 count testing even if their viral loads arepersistently suppressed, because disease progression can occur despite an undetectable viral load.

• Resistance-associated viral mutations to INSTIs, PIs, or NRTIs may develop in persons with HIV-2 while they are on ART. However,no validated HIV-2 genotypic or phenotypic antiretroviral resistance assays are approved for clinical use.

• In the event of virologic, immunologic, or clinical failure, a new ART regimen should be constructed in consultation with an expert inHIV-2 management.

• Antiretroviral therapy (ART) is recommended for all people with HIV regardless of CD4 T lymphocyte cell count (AI). ART is especially important for older individuals because they have a greater risk of serious non-AIDS complications and potentially a blunted immunologic response to ART.

• Given that the burden of aging-related diseases is significantly higher among persons with HIV than in the general population, additional medical and social services may be required to effectively manage both HIV and comorbid conditions.

• Adverse drug events from ART and concomitant drugs may occur more frequently in older persons with HIV than in younger individuals with HIV. Therefore, the bone, kidney, metabolic, cardiovascular, cognitive, and liver health of older individuals with HIV should be monitored closely.

• Polypharmacy is common in older persons with HIV; therefore, there is a greater risk of drug-drug interactions between antiretroviral drugs and concomitant medications. Potential for drug-drug interactions should be assessed regularly, especially when starting or switching ART and concomitant medications.

• The decline in neurocognitive function with aging is faster in people with HIV than in people without HIV. HIV-associated neurocognitive disorder (HAND) is associated with reduced adherence to therapy and poorer health outcomes including increased risk of death. For persons with progressively worsening symptoms of HAND, referral to a neurologist for evaluation and management or a neuropsychologist for formal neurocognitive testing may be warranted (BIII).

• Mental health disorders are a growing concern in aging people with HIV. A heightened risk of mood disorders including anxiety and depression has been observed in this population. Screening for depression and management of mental health issues are critical in caring for persons with HIV.

• HIV experts, primary care providers, and other specialists should work together to optimize the medical care of older persons with HIV and complex comorbidities.

• Early diagnosis of HIV and counseling to prevent secondary transmission of HIV remains an important aspect of the care of older people with HIV

• Substance use disorders (SUDs) are prevalent among people with HIV and contribute to poor health outcomes; therefore, screening for SUDs should be a routine part of clinical care (AII).

• The most commonly used substances among people with HIV include alcohol, benzodiazepines, cannabinoids, club drugs, opioids, stimulants (cocaine and methamphetamines), and tobacco.

• Health care providers should be nonjudgmental when addressing substance use with their patients (AIII).

• People with HIV and SUDs should be screened for additional mental health disorders (AII).

• People with HIV and SUDs should be offered evidenced-based pharmacotherapy (e.g., opioid agonist therapy, tobacco cessation treatment, alcohol use disorder treatment; see Table 16 below) as part of comprehensive HIV care in HIV clinical settings (AI).

• Ongoing substance use is not a contraindication to antiretroviral therapy (ART) (AI). Persons who use substances can achieve and maintain viral suppression with ART.

• Substance use may increase the likelihood of risk-taking behaviors (e.g., risky sexual behaviors), the potential for drug-drug interactions, and the risk or severity of substance-associated toxicities (e.g., increased hepatotoxicity or an increased risk of overdose).

• Selection of antiretroviral (ARV) regimens for individuals who practice unhealthy substance and alcohol use should take into account potential adherence barriers, comorbidities that could impact care (e.g., advanced liver disease from alcohol or hepatitis viruses), potential drug-drug interactions, and possible adverse events associated with the medications (AII).

• ARV regimens with once-daily dosing of single-tablet regimens, high barriers to resistance, low hepatotoxicity, and low potential for drug-drug interactions are preferred (AIII).

• Antiretroviral therapy (ART) is recommended for all transgender people with HIV to improve their health and to reduce the risk of HIV transmission to sexual partners (AI).

• HIV care services should be provided within a gender-affirmative care model to reduce potential barriers to ART adherence and to maximize the likelihood of achieving sustained viral suppression (AII).

• Prior to ART initiation, a pregnancy test should be performed for transgender individuals of childbearing potential (AIII).

• Some antiretroviral drugs may have pharmacokinetic interactions with gender-affirming hormone therapy. Clinical effects and hormone levels should be routinely monitored with appropriate titrations of estradiol, testosterone, or androgen blockers, as needed (AIII).

• Gender-affirming hormone therapies are associated with hyperlipidemia, elevated cardiovascular risk, and osteopenia; therefore, clinicians should choose an ART regimen that will not increase the risk of these adverse effects (AIII).

• Antiretroviral therapy (ART) is recommended for all people living with HIV to improve their health and to reduce the risk of HIV transmission to sexual partners without HIV (AI).

• When prescribing antiretroviral (ARV) drugs for women with HIV, clinicians should consider that some ARV drugs have significant pharmacokinetic (PK) interactions with hormonal contraceptives (AII) and hormone replacement therapy (BIII). Consult Tables 24a, 24b, 24d, and 24e for detailed recommendations and a summary of available data when selecting ARV and hormone combination therapy (AIII).

• Clinicians should consider the possibility of weight gain in women when initiating or changing ART, because women in general and Black women in particular experience greater weight gain with ART over time than men (AI).

• A pregnancy test should be performed for women of childbearing potential before initiation of ART, and choice of ART should be guided by recommendations from the Perinatal Guidelines (AIII).

• When selecting or evaluating an ARV regimen for women with HIV of childbearing potential, consider the regimen’s effectiveness, the woman’s hepatitis B status, the teratogenic potential of the drugs in the ARV regimen, and the possible adverse outcomes for the mother and fetus (AII).

• During pregnancy, an additional goal of ART is to maintain a viral load below the limit of detection throughout pregnancy to reduce the risk of transmission to the fetus and newborn (AI).

• When selecting an ARV combination regimen for a pregnant woman, clinicians should consider the available safety, efficacy, and PK data on use during pregnancy for each agent. The risks and benefits of ARV use during pregnancy should be discussed with all individuals of childbearing potential (AIII), and clinicians should consult the most current Perinatal Guidelines when designing a regimen (AIII).

• Before initiation of antiretroviral therapy (ART), all patients who test positive for hepatitis B surface antigen (HBsAg) should be tested for hepatitis B virus (HBV) DNA using a quantitative assay to determine the level of HBV replication (AIII).

• Because emtricitabine (FTC), lamivudine (3TC), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) have activity against both HIV and HBV, an ART regimen for patients with both HIV and HBV should be include (TAF or TDF) plus (3TC or FTC) as the nucleoside reverse transcriptase inhibitor (NRTI) backbone of a fully suppressive antiretroviral (ARV) regimen (AI).

• If TDF or TAF cannot safely be used, the alternative recommended HBV therapy is entecavir in addition to a fully suppressive ARV regimen (BI). Entecavir has activity against HIV; its use for HBV treatment without ART in patients with dual infection may result in the selection of the M184V mutation that confers HIV resistance to 3TC and FTC. Therefore, entecavir must be used in addition to a fully suppressive ARV regimen when given to patients with HBV/HIV-coinfection (AII). Peginterferon alfa monotherapy may also be considered in certain patients (CII).

• Other HBV treatment regimens, including adefovir alone or in combination with 3TC or FTC and telbivudine, are not recommended for patients with HBV/HIV coinfection (CII).

• Discontinuation of agents with anti-HBV activity may cause serious hepatocellular damage resulting from reactivation of HBV; patients should be advised against stopping these medications and be carefully monitored during interruptions in HBV treatment (AII).

• If ART needs to be modified due to HIV virologic failure and the patient has adequate HBV suppression, the ARV drugs active against HBV should be continued for HBV treatment in combination with other suitable ARV agents to achieve HIV suppression (AIII).

• HBV reactivation has been observed in persons with HBV infection during interferon-free HCV treatment. For that reason, all patients initiating HCV therapy should be tested for HBV. Persons with HCV/HIV coinfection and active HBV infection (determined by a positive HBsAg test) should receive ART that includes two agents with anti-HBV activity prior to initiating HCV therapy (AIII).

•All people with HIV should be screened for hepatitis C virus (HCV) infection (AIII). Patients at high risk of HCVinfection should be screened annually and whenever incident HCV infection is suspected (AIII).

•Antiretroviral therapy (ART) may slow the progression of liver disease by preserving or restoring immunefunction and reducing HIV-related immune activation and inflammation. For most persons with HCV/HIVcoinfection, including those with cirrhosis, the benefits of ART outweigh concerns regarding drug-induced liverinjury. Therefore, ART should be initiated in all patients with HCV/HIV coinfection, regardless of CD4 Tlymphocyte cell count (AI).

•Initial ART regimens that are recommended for most patients with HCV/HIV coinfection are the same as thoserecommended for individuals without HCV infection. However, when treatment for both HIV and HCV isindicated, the ART and HCV treatment regimens should be selected with special consideration for potentialdrug-drug interactions and overlapping toxicities (AIII) (see discussion in the text below and in Table 18).

•All patients with HCV/HIV coinfection should be evaluated for HCV therapy, which includes assessing their liverfibrosis stage to guide the duration of therapy and predict subsequent risk of hepatocellular carcinoma and liverdisease complications (AIII).

•Persons with chronic HCV/HIV coinfection should be screened for active and prior hepatitis B virus (HBV)infection by testing for the presence of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B surface(HBsAb) and core (HBcAb; total or Immunoglobulin G). Persons who are not immune to HBV infection (HBsAbnegative) should receive anti-HBV vaccination (AIII).

•HBV reactivation has been observed in persons with HBV infection during HCV treatment with direct-actingantivirals. Accordingly, before initiating HCV therapy, persons with HCV/HIV coinfection and active HBVinfection (HBsAg positive) should receive ART that includes two agents with anti-HBV activity (AIII).

Selection of tuberculosis (TB)-preventive treatment for individuals with HIV and latent tuberculosis infection (L TBI) should be based on the individual’s antiretroviral (ARV) regimen as noted below.

• With daily isoniazid alone for 6 or 9 months, any ARV regimen can be used (AIII).
• With once-weekly isoniazid plus rifapentine for 3 months:
◦ Efavirenz (EFV) 600 mg once daily or raltegravir 400 mg twice daily (in combination with either abacavir/lamivudine [ABC/3TC] or tenofovir disoproxil fumarate/emtricitabine [TDF/FTC]) can be used (AII).
◦ Dolutegravir (DTG) 50 mg once daily may be used for those in whom once-daily DTG is appropriate (BII). This 3-month regimen is not recommended for patients who require twice-daily DTG therapy (e.g., those with certain integrase strand transfer inhibitors [INSTI]-associated resistance substitutions or clinically suspected INSTI resistance) (AIII).

• With once-daily isoniazid and rifapentine for 1 month:
◦ EFV 600 mg once daily (in combination with either ABC/3TC or TDF/FTC) can be used without dose adjustment (AI).

• If rifampin or rifapentine is used to treat L TBI, clinicians should review Tables 24a through 24e to assess the potential for drug-drug interactions among different ARV drugs and the rifamycins (AII).


All patients with HIV and active TB who are not on antiretroviral therapy (ART) should be started on ART as described below.

• CD4 T lymphocyte (CD4) cell counts <50 cells/mm3: Initiate ART as soon as possible, but within 2 weeks of starting TB treatment (AI).

• CD4 counts ≥50 cells/mm3: Initiate ART within 8 weeks of starting TB treatment (AI).

• During pregnancy, regardless of CD4 count: Initiate ART as early as feasible, for treatment of the person with HIV and to prevent HIV transmission to the infant (AIII).

• With TB meningitis: When initiating ART early, patients should be closely monitored, as high rates of adverse events and deaths have been reported in a randomized trial (AI).

• For patients with active TB who are receiving ART, the ARV regimen should be assessed with particular attention to potential drug-drug interactions between ARVs and TB drugs. Rifamycin antibiotics (rifabutin, rifampin, and rifapentine), in particular, have considerable potential for drug-drug interactions. The ARV regimen may need to be modified to permit use of the optimal TB treatment regimen (see Tables 24a through 24e for drug interaction data and dosing recommendations). (AII).

• Linkage-to-care and adherence to both antiretroviral therapy (ART) and clinic appointments should be regularly assessed.

• An individual’s barriers to adherence to ART and appointments should be assessed before initiation of ART and regularly thereafter.

• Patients with ART adherence problems should be placed on regimens with high genetic barriers to resistance, such as dolutegravir (DTG) or boosted darunavir (DRV). Side effects, out-of-pocket costs, convenience, and patient preferences also need to be considered.

• Patients having difficulties with adherence to appointments or ART should be approached in a constructive, collaborative, nonjudgmental, and problem-solving manner.

• The approach to improved adherence should be tailored to each person’s needs (or barriers to care). Approaches could include, but are not limited to:
• Changing ART to simplify dosing or reduce side effects
• Finding resources to assist with treatment costs to maintain uninterrupted access to both ART and appointments
• Allowing flexible appointment scheduling
• Assisting with transportation, or
• Linking patients to counseling to overcome stigma, substance use, or depression.

• Multidisciplinary approaches to find solutions to ART and appointment adherence problems are often necessary, including collaboration with social work and case management (to the extent available). The clinician’s role is to help the patient understand the importance of adherence to the continuum of care and reveal barriers to adherence, and link the patient to resources to overcome those barriers.

• A summary of best practice interventions to improve linkage, retention, and adherence can be found at a Centers for Disease Control and Prevention compendium (https://www.cdc.gov/hiv/research/interventionresearch/compendium/index.html).