Guidelines for the Use of Antiretroviral Agents in Adults and ...

Guidelines for the Use of Antiretroviral Agents in Adults and ...

Special Issues Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents January 2016 AETC NCRC Slide Set About This Presentation These slides were developed using the April 2015 guidelines, and updated in July 2016. The intended audience is clinicians involved in the care of patients with HIV. Because the field of HIV care is rapidly changing, users are cautioned that the information in this presentation may become out of date quickly. It is intended that these slides be used as prepared, without changes in either content or attribution. Users are asked to honor this intent. AETC NCRC July 2016 2 Special Issues: Contents Early HIV Infection Adolescents Women Illicit Drug Users HIV-2 Infection Hepatitis B or C Coinfection Mycobacterium Tuberculosis Preventing Secondary Transmission

July 2016 3 Early HIV Infection Acute HIV infection Initial phase of infection; HIV RNA and p24 Ag are present but anti-HIV antibodies are undetectable Recent infection The phase up to 6 months after infection; anti-HIV antibodies are detectable July 2016

4 Early HIV Infection: Acute Retroviral Syndrome 40-90% have symptoms of acute retroviral syndrome but acute HIV often not recognized Maintain high level of suspicion in patients with compatible clinical syndrome plus risks Fever Lymphadenopathy Pharyngitis Rash Myalgia or arthralgia Diarrhea

Headache Nausea and vomiting Hepatosplenomegaly Weight loss Thrush Neurological symptoms July 2016 5 Acute HIV Infection: Diagnosis Usually, detectable HIV RNA or p24 antigen with negative or indeterminate HIV antibody test result Combination HIV Ag/Ab tests Detect HIV-1 and HIV-2 and HIV-1 p24 Ag Recommended by CDC as preferred assay for HIV screening, including for possible acute HIV-1

Reactive specimens should be tested with assay that differentiates HIV-1 and HIV-2 If reactive on Ag/Ab test but negative or indeterminate on Ab differentiation test: retest with quantitative or qualitative HIV-1 RNA test If negative on RNA test: Ag/Ab was falsely positive If positive: likely acute HIV-1; consider ART Confirm HIV-1 infection with subsequent testing to document HIV Ab seroconversion July 2016 6 Acute HIV Infection: Diagnosis (2) If initial testing done with assay that tests only HIV Ab: If Ab is negative or indeterminate but acute HIV is

suspected: Check HIV RNA: if positive, presumptive diagnosis is acute HIV-1 Low-positive HIV RNA (<10,000 copies/mL) may be false positive repeat test on different specimen If diagnosis is made by HIV RNA testing, confirm diagnosis with subsequent Ab testing July 2016 7 Early HIV Infection: Treatment ART recommended for all persons with HIV, including early HIV infection

Limited outcome data from clinical trials July 2016 8 Early HIV Infection: Treatment (2) Possible benefits: Decrease severity of acute disease Lower viral set point Reduce viral reservoir Delay disease progression Enhance CD4 cell recovery Reduce rate of viral mutation Lower risk of HIV transmission Lessen loss of GI lymphoid tissue July 2016 9 Early HIV Infection: Transmitted Resistance Transmitted virus may be resistant to 1 ARV drugs in up to 16% of patients with acute HIV infection Perform resistance testing at baseline to guide ARV selection (genotype) Treatment initiation should not be delayed pending genotype results (regimen can be modified if indicated) July

2016 10 Early HIV Infection: Treatment Regimen ARV regimen recommendations and monitoring are same as for chronic infection If treatment is begun before resistance test results are available, use boosted PI (transmitted resistance is uncommon, and new resistance emerges slowly) May consider dolutegravir (DTG) + TDF/FTC Data on transmission of integrase resistance and on efficacy of this regimen in acute infection are limited If early infection in person taking TDF/FTC as PrEP, also consider boosted PI or DTG while genotype results are pending

July 2016 11 The HIV-Infected Adolescent Heterogeneous group in numerous respects Most acquired HIV though sexual risk behaviors 26% of new HIV infections in United States are estimated to occur in youth aged 13-26 (2010) 57% of these are in young black/African Americans 75% in young MSM In 2010, CDC estimated that 60% of HIV-infected youth were undiagnosed Some infected perinatally or via blood products Usually heavily treatment experienced July 2016 12 The HIV-Infected Adolescent (2) ART recommended for all Readiness and ability to adhere to ART should be carefully considered Support is needed to reduce barriers to adherence and maximize ART success July 2016

13 The HIV-Infected Adolescent (3) Adult guidelines for ART usually appropriate for postpubertal adolescents Dosing should be based on sexual maturity rating (SMR)/Tanner stages Use adult dosing schedules for those in late puberty Youth have lower rates of viral suppression, higher rates of virologic rebound and loss to follow-up follow-up July 2016 14

The HIV-Infected Adolescent (4) Challenges to adherence: Denial and fear of HIV infection Misinformation Distrust of the medical establishment Fear and lack of belief in the effectiveness of medications Low self-esteem Unstructured and chaotic lifestyles Lack of familial and social support Unavailable or inconsistent access to care July 2016 15

The HIV-Infected Adolescent (5) Special considerations: Preventing (and screening for) STDs (including HPV) Family planning counseling For females, gynecologic care, contraception (including interactions with ARVs); avoid EFV For transgender youth, sensitive psychosocial and health supports Prevention of HIV transmission July 2016 16

The HIV-Infected Adolescent (6) Transitioning care: Recognize differences between many adolescent and adult HIV care models Consider issues of independence, autonomy, decisional capacity, confidentiality, consent, medical insurance Recognize different biomedical and psychosocial needs of perinatally infected vs behaviorally infected youth July 2016 17

The HIV-Infected Adolescent (7) Facilitators to successful transitioning: Optimize communication between adolescent and adult providers, including multidisciplinary case conferences Address patient/family resistance (eg, owing to knowledge deficits, stigma, disclosure, differences in practice styles) Prepare youth for life-skills development (eg, appropriate use of care providers, medication management) Identify optimal clinic model Evaluate success of care model Include interventions that improve outcomes (eg, support groups and mental health consultation) Incorporate a family planning component July 2016 18

HIV-Infected Women ART recommended for all HIV-infected women, for their health and to reduce transmission to HIV-uninfected sex partners In general, no sex differences in virologic efficacy of ART Some evidence of sex differences in metabolism and response to some ARVs Increased risk of certain ARV adverse effects: NVP-associated hepatotoxicity (especially if initiated at CD4 count >250 cells/L); NVP not recommended Lactic acidosis: d4T + ddI; these are not recommended Metabolic complications: eg, lipoaccumulation, elevated triglycerides, osteopenia/osteoporosis July 2016

19 HIV-Infected Women (2) Women of childbearing potential Offer preconception counseling and care Offer effective counseling and contraception to prevent unintended pregnancy For HIV-infected women who wish to conceive: inform as to options for preventing sexual transmission of HIV while attempting conception Interventions include: Screening and treatment for STDs (both partners) ART and virologic suppression PrEP (Pre-exposure prophylaxis) for uninfected partner Male circumcision Self-insemination with HIV-uninfected male partners sper m July

2016 20 HIV-Infected Women (3) Efavirenz Teratogenic in nonhuman primates Risk of neural tube defects occurs during the first 5-6 weeks of pregnancy, and pregnancy usually is not recognized before 4-6 weeks of pregnancy Do pregnancy test before starting EFV (women of childbearing potential) Counsel about potential risk to fetus and desirability of avoiding pregnancy while on EFV Consider alternative ARV agent in women who are trying to conceive or who are not using effective contraception, if feasible

July 2016 21 HIV-Infected Women: Contraception ARV interactions with hormonal contraceptives: Oral agents: PIs, EFV, and elvitegravir/cobicistat may increase or decrease levels of ethinyl estradiol, norethindrone, and norgestimate, and may cause contraceptive failure or estrogen or progestin adverse effects Consider alternative or additional contraceptive method if used with interacting ARVs Few data on transdermal patch, vaginal ring: cautions as above DMPA: few data; no significant interactions with EFV, NVP, LPV/r, NFV, NRTIs Implants: EFV may decrease levonorgestrel and etonogestrel

levels and cause contraceptive failure IUD: safe and effective July 2016 22 HIV-Infected Women: Contraception (2) Hormonal contraception and HIV infection risk: Conflicting data; in one study of serodiscordant couples, DMPA associated with risk of acquiring HIV (for HIV-uninfected women) and transmitting HIV (for HIV-infected women); no significant association with oral contraceptive use (small numbers); no participants were on ART

Other studies have not observed association of hormonal contraception and HIV transmission or acquisition July 2016 23 HIV-Infected Women: Contraception (3) Consistent use of condoms (male or female) recommended to reduce risk of HIV transmission and STD acquisition, regardless of contraceptive use ART and suppression of HIV viremia is recommended to reduce HIV transmission risk July 2016 24 Treatment for Pregnant Women* Combination ART recommended for all HIVinfected pregnant women, regardless of CD4 count, HIV viral load, or clinical status Counsel on known benefits and risks of ART during pregnancy * See also the U.S. Public Health Services Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United States.

July 2016 25 ART for Pregnant Women (2) To reduce risk of perinatal transmission: Combination ART, with maximal and sustained suppression of HIV RNA levels during pregnancy Perform resistance testing before starting ART, and for women on ART with detectable HIV RNA ART initiation should not be delayed pending resistance test results; modify ARV regimen if indicated based on test results July 2016

26 ART for Pregnant Women (3) Regimen considerations: Potential PK changes caused by pregnancy, different dosing requirements Potential adverse effects of ARVs on pregnant women Potential short- and long-term ARV effects on the fetus and newborn July 2016 27

ART for Pregnant Women (4) Efavirenz Risk of neural tube defects in first 5-6 weeks of pregnancy Because pregnancy is rarely recognized before 4-6 weeks of pregnancy, and changes in ARVs may increase risk of loss of viral control and risk of perinatal transmission, EFV can be continued in pregnant women who present in the first trimester on a virologically suppressive regimen that includes EFV July 2016 28

ART for Pregnant Women (5) Zidovudine: IV ZDV infusion recommended during labor if maternal HIV RNA is 1,000 copies/mL (or is unknown) near time of delivery July 2016 29 ART for Pregnant Women (6) Report cases of prenatal ARV exposure to the Antiretroviral Pregnancy Registry ( See U.S. PHS Task Force Guidelines for Use of

Antiretroviral Drugs in Pregnant HIV-1-Infected Women July 2016 30 Postpartum Management Continue ART after delivery, as for all HIVinfected persons Note that ART adherence may worsen postpartum; specifically address and support adherence Breast-feeding is not recommended, owing to risk of postnatal transmission HIV-infected women should avoid premastication of food for the infant: associated with HIV

transmission to child July 2016 31 HIV and the Older Patient In the U.S., approximately 30% of HIV-infected persons are 50 years of age Aging-related comorbidities may complicate management of HIV HIV may increase risk of comorbidities and may accelerate the aging process Limited data on effects of ARVs in older persons (eg, adverse effects, drug-drug interactions)

July 2016 32 HIV and the Older Patient: HIV Risk, Diagnosis, and Prevention Reduced mucosal and immunologic defenses and changes in risk behaviors may lead to increased risk of HIV acquisition and transmission HIV screening rates in older persons are low Older persons may have more advanced HIV at presentation and ART initiation Screen for HIV per CDC recommendations Sexual history, risk-reduction counseling, screening for STIs (as indicated) are important to general health care for HIV-infected and HIV-uninfected older persons

July 2016 33 HIV and the Older Patient: ART ART is recommended in patients >50 years of age, regardless of CD4 cell count (BIII) Older persons have decreased immune recovery and increased risk of non-AIDS events No data on specific ARVs in older persons; individualize ARV selection Monitor ART effectiveness and safety per general guidelines, but give special attention to renal, liver, cardiovascular, metabolic, and bone health

July 2016 34 HIV and the Older Patient: ART (2) CD4 cell recovery on ART may be less robust in older patients (though virologic response appears to be the same as in younger patients) Starting ART at younger age may result in better outcomes (immunologic and perhaps clinical) Interactions between ARVs and other medications, as well as polypharmacy, may complicate care July 2016

35 HIV and the Older Patient: ART (3) Adherence: Some data suggest older HIV-infected patients may be more adherent to ART than younger patients However, many issues (eg, complex dosing requirements, cost, limited health literacy, neurocognitive impairment) may impact adherence Assess adherence regularly; facilitate adherence July 2016 36

HIV and the Older Patient: Complications and Comorbidities Non-AIDS illnesses (eg, cardiovascular disease, liver disease, cancer, bone fragility, and neurocognitive impairment) may have increased disease burden in aging HIV-infected persons Current primary care recommendations advise to identify and manage risks in HIV-infected as in HIV-uninfected individuals July 2016 37 Illicit Drug Users Transmission via injection drug use is second

most common HIV transmission route in U.S. Noninjection illicit drug use may facilitate sexual transmission of HIV HIV infection most associated with heroin and stimulants (eg, cocaine and amphetamines); amyl nitrate and other club drugs also associated July 2016 38 Illicit Drug Users (2) HIV-infected injection and noninjection drug users

Often have multiple comorbidities Increased morbidity and mortality Increased risk of overdose than HIV-uninfected drug users Decreased access to HIV care Less likely to receive ART July 2016 39 Illicit Drug Users: Efficacy of HIV Treatment In drug users who are not actively using, efficacy similar to that of other populations

Active drug use may interfere with adherence and ART success In some patients, substance abuse treatment may be required for ART success Many other support mechanisms may be effective Injection drug users may have more ARV-related adverse effects July 2016 40 Treatment of Opioid Addiction: Interactions with ARVs Methadone: may interact significantly with ART

NRTIs: no significant effects on methadone levels; ZDV levels increased NNRTIs: EFV and NVP decrease methadone levels PIs: may decrease methadone levels; methadone decreases amprenavir levels Integrase inhibitors: no significant effects on methadone levels (except EVG + PI/r may decrease levels) July 2016 41 Treatment of Opioid Addiction: Interactions with ARVs (2) Buprenorphine: limited data; interacts with some

PIs and NNRTIs ATV and TPV/r levels decreased, do not use with unboosted ATV Buprenorphine levels increased by ATV/r, DRV/r (effect of cobicistat not studied) Buprenorphine levels decreased by EFV, modestly by ETR Naltrexone: no expected interactions with PIs or NNRTIs July 2016 42 HIV-2 Infection

Endemic in West Africa, and rates are high in countries with strong socioeconomic ties to West Africa (eg, France, Spain, Portugal, Brazil and other former Portuguese colonies) Consider in persons who originated in these areas or who have had sex or needle-sharing partners from these areas July 2016 43 HIV-2 Infection (2) Compared with HIV-1: Usually longer asymptomatic stage, lower plasma HIV-2 RNA levels, lower mortality rates

Can progress to AIDS Coinfection with HIV-1 and HIV-2 is possible; consider if patient is from a high-prevalence area Also consider (in appropriate epidemiologic setting) if: Atypical serologic findings (eg, positive screening test with indeterminate HIV-1 Western blot) Low or undetectable HIV-1 RNA Declining CD4 count despite apparent virologic suppression on ART July 2016 44 HIV-2 Infection (3)

Testing: CDC recommends initial test with HIV-1/HIV-2 Ag/Ab immunoassay, and subsequent testing with HIV-1/HIV-2 Ab differentiation immunoassay Multispot HIV-1/HIV-2 Rapid Test is approved for differentiating HIV-1 and HIV-2 Commercially available HIV-1 viral load assays do not reliably detect or quantify HIV-2 HIV-2 RNA assays are available from University of Washington and N.Y. State Department of Health Approximately 1/4-1/3 of untreated HIV-2-infected patients will have HIV-2 RNA levels below the limits of detection; some may have CD4 decline and clinical progression No validated HIV-2 genotype or phenotype assays July

2016 45 HIV-2 Infection: ART Optimal treatment strategy not defined: no randomized controlled trials on when to start ART or on specific ARVs ART should be started before there is clinical progression Activity of some ARVs is different in HIV-2 infection July 2016 46

HIV-2 Infection: ART (2) ARV activity NRTIs: active, though lower barrier to resistance than with HIV-1 (in vitro data) NNRTIs and enfuvirtide: HIV-2 is intrinsically resistant; do not use PIs: DRV/r, LPV/r, SQV/r have greatest activity; others should be avoided INSTIs: potent activity CCR5 antagonist (MVC) appears active against some isolates, but: No approved assays to determine HIV-2 coreceptor tropism HIV-2 uses multiple minor coreceptors in addition to CCR5 and CXCR4 July 2016

47 HIV-2 Infection: Treatment Considerations Limited controlled trial data on initial ART options: use 2 NRTIs + HIV-2-active boosted PI or INSTI, pending availability of further data Use HIV-2 RNA levels, CD4 count, clinical status to assess treatment response CD4 recovery on ART may be poor Resistance-associated mutations develop commonly on ART Genotype interpretation algorithms may not be applicable to HIV-2 In the event of treatment failure, consult with an expert in HIV-2 management July

2016 48 HBV/HIV Coinfection 5-10% of HIV-infected persons in the United States have chronic HBV infection Progression of HBV is faster with HIV coinfection (cirrhosis, ESLD, hepatocellular carcinoma [HCC]) HBV does not alter progression of HIV infection or efficacy of ART In HBV/HIV-coinfected patients, liver toxicity from ARVs and flares of HBV may complicate HIV treatment July 2016

49 HBV/HIV Coinfection and ART Considerations in ART: FTC, 3TC, TAF, and TDF are active against both HIV and HBV Discontinuation may cause HBV flares HBV resistance to 3TC monotherapy 40% at 2 years, 90% at 4 years 3TC or FTC should be used in combination with other anti-HBV drugs Entecavir has activity against HIV; may select for M184V mutation, conferring cross-resistance to 3TC and FTC Use only with fully suppressive ARV regimen

July 2016 50 HBV/HIV Coinfection and ART (2) Immune reconstitution may result in transaminase elevation Patients with immune reconstitution may have loss of envelope antigen (HBeAg), associated with HBV flare Some ARVs may increase transaminase levels; ARV toxicity may be difficult to distinguish from HBV flare (and possible precursor to HBeAg seroconversion)

July 2016 51 HBV/HIV Coinfection: Treatment Recommendations For all HBV/HIV-coinfected patients: Counsel avoidance of alcohol Vaccinate against hepatitis A (if not immune) Advise on methods to prevent HBV transmission Evaluate severity of HBV infection July 2016

52 HBV/HIV Coinfection: Treatment Recommendations (2) For all with positive HBsAg: Quantitative test for HBV DNA before ART initiation If already on ART with HBV-active agents, quantitative HBV DNA test every 6-12 months to monitor HBV treatment efficacy July 2016 53 HBV/HIV Coinfection:

Treatment Recommendations (3) If not yet on treatment and HBV or HIV treatment is needed: Treat both infections by starting an ARV regimen that includes TDF/FTC or TAF/FTC (or TDF + 3TC) as NRTI backbone Avoid HBV monotherapy, to avoid HBV resistance TAF appears to cause less renal toxicity and less loss of bone mineral density than TDF July 2016 54 HBV/HIV Coinfection: Treatment Recommendations (4)

Alternative regimens (if TDF or TAF cannot be used safely): Entecavir + a fully suppressive ARV regimen Entecavir should not be considered part of ARV regimen If 3TC resistance is suspected, monitor closely, increase entecavir dosage; entecavir resistance may develop quickly Consider pegylated interferon-alfa for certain patients (no anti-HIV activity) Adefovir and telbivudine no longer recommended for HBV/ HIV coinfection Use in combination with suppressive ARV regimen July 2016

55 HBV/HIV Coinfection: Treatment Recommendations (5) Need to discontinue medications active against HBV Severe flares of HBV possible; monitor LFTs closely Consider entecavir (with suppressive ART) to prevent flares, especially if hepatic reserve is marginal Need to change ART because of HIV resistance: If adequate HBV suppression, continue the ARVs with activity against HBV; combine with other suitable ARVs to achieve HIV suppression July 2016

56 HCV/HIV Coinfection Higher rates of progressive liver disease Unclear whether HCV increases HIV progression ART may slow progression of liver disease ART is recommended for all coinfected patients, regardless of CD4 count If CD4 count low (eg, <200 cells/L), start ART quickly; may delay HCV therapy until stable on ART For most patients, benefits of ART outweigh concerns about ARV-associated hepatotoxicity July 2016

57 HCV/HIV Coinfection: ART Recommendations for initial ARV regimens are the same as for patients without HCV infection But, carefully consider potential drug-drug interactions with HCV therapies, or overlapping toxicities; some combinations are contraindicated Higher risk of hepatotoxicity with some older ARVs Avoid d4T, ddI, AZT, NVP, TPV if possible Hepatically metabolized ARVs may require dosage modification or avoidance in patients with cirrhosis July 2016

58 HCV/HIV Coinfection: HCV Treatment Concurrent treatment of HIV and HCV is possible, but may be complicated (pill burden, drug interactions, overlapping drug toxicities) Evaluate all coinfected patients for HCV therapy Perform genotype testing and liver disease staging Disease stage helps determine need for HCV treatment Consider potential interactions between HIV and HCV medications; modify ART if necessary July 2016

59 HCV/HIV Coinfection: HCV Treatment (2) Treatment with pegylated interferon + ribavirin (Peg-IFN/RBV) associated with poor rate of HCV clearance (sustained virologic response, SVR) Direct-acting antiviral (DAA) agents improve HCV response rates July 2016 60 HCV/HIV Coinfection: HCV Treatment (3) Newer DAAs Simeprevir (NS3/4A protease inhibitor)

Cannot be given with EFV, ETR, HIV protease inhibitors, COBI, or EFG/COBI/TDF/FTC Can be given with RAL, DTG, RPV, TDF Sofosbuvir (NS5B nucleotide polymerase inhibitor) Can be used with most ARVs, except TPV Ledipasvir (NS5A inhibitor) Available in fixed-dose combination with sofosbuvir Compatible with most ARVs Coadministration with TDF + RTV or COBI may increase TDF exposure; caution in patients with renal disease; monitor for renal toxicity July 2016 61

HCV/HIV Coinfection: HCV Treatment (4) Newer DAAs (cont.) Daclatasvir (NS5A inhibitor) Approved for use with sofosbuvir EFV, ETR, NVP reduce daclatasvir levels; daclatasvir dosage must be increased Some boosted PIs (eg, ATV/r or ATV/c) increase daclatasvir levels; daclatasvir dosage must be reduced No dosage adjustment needed with boosted DRV, RPV, DTG, or RAL Elbasvir (NS5A inhibitor) + grazoprevir (HCV PI) Cannot be given with EFV, ETR, NVP, boosted PIs, or elvitegravir/cobicistat Can be given with RPV, DTG, and RAL July

2016 62 HCV/HIV Coinfection: HCV Treatment (5) Newer DAAs (cont.) Ombitasvir (NS5A inhibitor)/paritaprevir (HCV PI)/RTV + dasabuvir (NS5B inhibitor): copackaged combination regimen Significant and complex interactions with some ARVs: consider these carefully before administration May be used with ATV, DTG, RAL Approval of other DAA agents is expected soon July 2016

63 HCV/HIV Coinfection: Treatment (6) HCV treatment is evolving rapidly; consult with experts in treatment of HCV/HIV coinfection July 2016 64 HCV/HIV Coinfection: Other Management Issues Counsel patients to avoid alcohol Counsel on measures to reduce risk of HCV and HIV transmission to others

Check patients for immunity to hepatitis A and B, vaccinate if not immune July 2016 65 TB Disease in HIV-Infected Patients HIV infection increases risk of progression from latent to active TB: Risk increases as CD4 count declines TB increases HIV progression

July 2016 66 HIV and Latent TB infection Treatment for latent TB infection (LTBI) reduces risk of active TB Management of LTBI Exclude active TB disease Recommended LTBI treatments: Isoniazid (INH) daily or twice weekly x 9 months No interactions with ARVs INH + rifapentine once weekly x 12 weeks (directly observed therapy) Drug-drug interactions: can be used only with EFV and RAL, and ABC/ 3TC or TDF/FTC (not TAF/FTC)

Rifampin (or rifabutin) daily x 4 months Many drug-drug interactions: consult experts ART can prevent active TB July 2016 67 HIV and Latent TB infection (2) Immune reconstitution with ART may result in conversion of negative TST or interferon-gamma release assay (IGRA) to positive test Perform TST or IGRA for all patients before ART initiation If TST or IGRA is negative and CD4 count is <200 cells/L, repeat TB test after CD4 count increases to >200 cells/L on ART

Positive test result indicates latent TB infection (absent evidence of active TB); treat all for latent TB Rifapentine should not be used in persons on ART (unless through a clinical trial) July 2016 68 TB and HIV Coinfection: Treatment The treatment of TB in patients with HIV infection should follow the same principles as for the treatment of persons without HIV infection Initiate TB treatment immediately Directly observed therapy is strongly recommended

Initiate or optimize ART Concomitant therapy for both TB and HIV shown to reduce mortality Low CD4 count is risk factor for mortality IRIS more common if ART is initiated early in course of TB treatment, but not associated with mortality July 2016 69 TB and HIV Coinfection: ART Recommendations Patients not on ART: Immediately initiate TB treatment If CD4 count <50 cells/L: start ART within 2 weeks of

starting TB treatment If CD4 count 50 cells/L and clinical disease is severe: start ART within 8 weeks of starting TB treatment No data show harm in starting ART earlier July 2016 70 TB and HIV Coinfection: ART Recommendations (2) Pregnant women Start ART as early as feasible, for maternal health and to prevent perinatal transmission Consult with experts

TB meningitis Caution in starting ART early In one study, immediate ART associated with higher rate of adverse events vs deferral of ART x 2 months Documented MDR or XDR TB Optimal timing of ART initiation is not known; consult with experts July 2016 71 TB and HIV Coinfection: ART Recommendations (3) Patients on ART: Continue ART (should be fully suppressive)

Evaluate ARV regimen for interactions with TB drugs (ie, rifamycins); may need modifications July 2016 72 TB and HIV Coinfection: TB Treatment Considerations Rifamycins should be included in TB regimens, unless TB resistance or toxicity Many potential drug interactions between rifamycins and ARVs

July 2016 73 TB and HIV Coinfection: Drug-Drug Interactions Rifampin NRTIs: not recommended with TAF PIs: Do not coadminister NNRTIs: Do not coadminister with ETR, RPV; can be given with EFV INSTIs: Do not coadminister with EVG/COBI; increased dosage of DTG or RAL needed if given with rifampin MVC: Not recommended; requires dosage increase when used with rifampin

July 2016 74 TB and HIV Coinfection: Drug-Drug Interactions (2) Rifabutin NRTIs: Not recommended with TAF PIs: Dosage adjustment of rifabutin may be necessary NNRTIs: Not recommended with RPV; can be used with EFV, ETR, NVP; dosage adjustment of rifabutin may be necessary INSTIs: Do not coadminister with EVG/COBI; can be used with DTG, RAL MVC: requires dosage adjustment of MVC

July 2016 75 TB and HIV Coinfection: Drug-Drug Interactions (3) Rifapentine NRTIs: Not recommended with TAF PIs: Do not coadminister NNRTIs: Do not coadminister with ETR, NVP, RPV; can be used with EFV INSTIs: Do not coadminister with DTG, EVG/COBI; do not coadminister once-daily rifapentine with RAL July 2016

76 TB and HIV Coinfection: IRIS IRIS: worsening clinical status while on treatment for active TB More common after ART initiation, caused by immune reconstitution Occurs in 8-43% of patients with HIV/TB disease Predictors: CD4 counts of <50 cells/L, severe TB, ART initiation <30 days after start of TB treatment Infrequently associated with mortality July 2016 77

TB and HIV Coinfection: IRIS (2) Management Continue treatment for TB and HIV NSAIDs for mild-to-moderate symptoms Severe cases: corticosteroids July 2016 78 Preventing Secondary Transmission of HIV Prevention interventions are a key part of HIV care In the United States, the rate of new HIV infections remains stable

Risk behaviors have increased since availability of effective ART Sexually transmitted infections (STIs), genital irritation, substance and alcohol use, noncircumcision in men, and other conditions, can increase risk of HIV transmission Recent data show that ART substantially decreases risk of sexual transmission of HIV July 2016 79 Preventing Secondary Transmission of HIV (2) Essential components of HIV patient care:

Reinforce prevention messages Assess patients understanding of HIV transmission Assess patients HIV transmission behaviors Discuss strategies to prevent transmission (individualize) Detect and treat STIs For women: Pregnancy prevention counseling with those who wish to avoid pregnancy Preconception counseling with those who wish to become pregnant July

2016 80 Preventing Secondary Transmission of HIV (3) Tools for prevention of sexual and bloodborne HIV transmission: Consistent and effective use of ART (with sustained suppression of HIV RNA) Consistent condom usage Safer sexual and drug-use practices Detection and treatment of STIs July 2016

81 Preventing Secondary Transmission of HIV (4) Interventions in clinic settings are effective in changing sexual risk behavior CDC training materials: Interventions also effective in reducing risky injection drug-use behavior Behavioral interventions and opiate substitution with methadone July 2016

82 Preventing Secondary Transmission of HIV: ART as Prevention ART may reduce risk of HIV transmission HIV viral load directly related to probability of HIV transmission; increased ART use and lower community viral load associated with lower HIV incidence Observational studies show lower rates of HIV transmission among serodiscordant heterosexual couples after viral suppression on ART July 2016 83

Preventing Secondary Transmission of HIV: ART as Prevention (2) ART may reduce risk of HIV transmission In a large RTC of HIV-discordant heterosexual couples, those on ART had 96% reduction in HIV transmission to uninfected partners No RTC data in MSM and IDUs But, HIV has been detected in genital secretions of persons with controlled plasma HIV RNA Belief in efficacy of ART may lead to increases in risk behavior July 2016 84

Websites to Access the Guidelines July 2016 85 About This Slide Set This presentation was prepared by Susa Coffey, MD, for the AETC National Resource Center and last updated in July 2016 for the AETC National Coordinating Resource Center. See the AETC NCRC website for the most current version of this presentation: July 2016 86

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