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Antiretroviral Management of the HIV-Infected Patient

Antiretroviral Management of the HIV-Infected Patient. Meg Sullivan, MD Section of Infectious Disease. Case #1. L.M. is a 26-year old man who has sex with men Last unprotected sexual contact 3 weeks ago He presents with a 1 week history of fever, rash, headache, sore throat, and diarrhea

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Antiretroviral Management of the HIV-Infected Patient

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  1. Antiretroviral Management of the HIV-Infected Patient Meg Sullivan, MD Section of Infectious Disease

  2. Case #1 • L.M. is a 26-year old man who has sex with men • Last unprotected sexual contact 3 weeks ago • He presents with a 1 week history of fever, rash, headache, sore throat, and diarrhea • HIV EIA reactive, HIV Western blot indeterminate, HIV RNA > 10 million copies/ml; CD4+ lymphocyte count 880/ml www.aidsetc.org

  3. Case #2 • C.A. is a 56-year-old Haitian woman • Presented to PCP with dysphagia • EGD demonstrated esophageal candidiasis • HIV EIA and WB reactive • CD4+ lymphocyte count 7/ml www.aidsetc.org

  4. Case #3 • N.C. is a 35-year-old homeless man • No regular shelter use • Recent IV heroin relapse • HIV test performed by OBOT provider • HIV EIA and WB reactive • CD+ lymphocyte count 418/ml www.aidsetc.org

  5. For which of these patients is antiretroviral therapy indicated? • What benefit would accrue to each? • For which might ART be postponed? Why? www.aidsetc.org

  6. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Developed by the Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working Group of the Office of AIDS Research Advisory Council (OARAC) www.aidsetc.org

  7. Goals of Treatment • Reduce HIV-related morbidity; prolong duration and quality of survival • Restore and/or preserve immunologic function • Maximally and durably suppress HIV viral load • Prevent HIV transmission www.aidsetc.org

  8. Rationale for ART • Effective ART with virologic suppression improves and preserves immune function, regardless of baseline CD4 count • Earlier ART may result in better immunologic responsesand clinical outcomes • Reduction in AIDS- and non-AIDS-associated morbidity and mortality • Reduction in HIV-associated inflammation and associated complications • ART can significantly reduce risk of HIV transmission-”Treatment as Prevention” • Recommended ARV combinations are effective andwell tolerated www.aidsetc.org

  9. When to Start ART • Exact CD4 count at which to initiate therapy not known, but evidence points to starting at higher counts • Current recommendation: ART for all www.aidsetc.org

  10. Recommendations for Initiating ART ART is recommended for treatment: • “ART is recommended for all HIV-infected individuals to reduce the risk of disease progression.” • The strength of this recommendation varies on the basis of pretreatment CD4 count (stronger at lower CD4 levels) www.aidsetc.org

  11. Rating Scheme for Recommendations • Strength of recommendation: • A: Strong • B: Moderate • C: Optional • Quality of evidence: • I: ≥1 randomized controlled trials • II: ≥1 well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes • III: Expert opinion www.aidsetc.org

  12. Recommendations for Initiating ART: CD4 Count or Clinical Category www.aidsetc.org

  13. Potential Benefits of Early Therapy: Supporting Data • CD4 count 350 cells/µL or history of AIDS-defining illness: • Randomized control trial (RCT) data show decreased morbidity and mortality with ART • CD4 count 350-500 cells/µL: • RCT data as well as nonrandomized trials and cohort data support morbidity and perhaps mortality benefit of ART www.aidsetc.org

  14. Potential Benefits of Early Therapy: Supporting Data (2) • CD4 count >500 cells/µL • Cohort study data are not consistent; some show survival benefit if ART initiated • Other considerations (eg, potential benefit of ART on non-AIDS complications, HIV transmission risk) support recommendation for ART www.aidsetc.org

  15. Potential Benefits of Early Therapy • Untreated HIV may be associated with development of AIDS and non-AIDS-defining conditions • Earlier ART may prevent HIV-related end-organ damage; deferred ART may not reliably repair damage acquired earlier • Increasing evidence of direct HIV effects on various end organs and indirect effects via HIV-associated inflammation • End-organ damage occurs at all stages of infection www.aidsetc.org

  16. Potential Benefits of Early Therapy (2) • Potential decrease in risk of many complications, including: • HIV-associated nephropathy • Liver disease progression from hepatitis B or C • Cardiovascular disease • Malignancies (AIDS defining and non-AIDS defining) • Neurocognitive decline • Blunted immunological response owing to ART initiation at older age • Persistent T-cell activation and inflammation www.aidsetc.org

  17. Consider More-Rapid Initiation of ART • Pregnancy • AIDS-defining condition • Acute opportunistic infection • Lower CD4 count (eg, <200 cells/µL) • Acute/recent infection • Rapid decline in CD4 • Higher viral load (eg, >100,000 copies/mL) • HIVAN • HBV coinfection • HCV coinfection www.aidsetc.org

  18. Potential Concerns about Early Therapy • ARV-related toxicities • Nonadherence to ART • Drug resistance • Cost www.aidsetc.org

  19. Recommendations for Initiating ART ART is recommended for Prevention: • “ART also is recommended for HIV-infected individuals for the prevention of transmission of HIV.” • “Treatment as Prevention” www.aidsetc.org

  20. HPTN 052 Study Design Stable, healthy, serodiscordant couples, sexually active CD4+ count: 350 to 550 cells/mm3 Randomization Immediate ART CD4 350-550 Delayed ART CD4 <250 Primary Transmission Endpoint Virologically-linked transmission events Primary Clinical Endpoint WHO stage 4 clinical events, pulmonary tuberculosis, severe bacterial infection and/or death

  21. HPTN 052: HIV-1 Transmission Breakdown Total HIV-1 Transmission Events: 39 Linked Transmissions: 28 Unlinked or TBD Transmissions: 11 • 23/28 (82%) transmissions in sub-Saharan Africa • 18/28 (64%) transmissions from female to male partners Immediate Arm: 1 Delayed Arm: 27 (p < 0.001) 96% efficacy

  22. Recommendations for Initiating ART: Prevention www.aidsetc.org

  23. Case #1 • Young MSM • Acute HIV infection • CD4 count preserved • Very high viral load • Should we treat him? • Why? www.aidsetc.org

  24. Benefits of treating LM • Preservation of CD4 count in normal range • ? Prevention of CV risk, HAND, malignancy • ? Prevention of transmission • High viral load associated with increased infectiousness • Prevention by ART not as well established for MSM as for heterosexual couples www.aidsetc.org

  25. Recommendations for Initiating ART: Considerations www.aidsetc.org

  26. LM is very distressed by the HIV diagnosis. He feels somewhat suicidal.Should we start ART today? www.aidsetc.org

  27. Consider Deferral of ART • Clinical or personal factors may support deferral of ART • If CD4 count is low, deferral should be considered only in unusual situations, and with close follow-up • When there are significant barriers to adherence • If comorbidities complicate or prohibit ART • “Elite controllers” and long-term nonprogressors www.aidsetc.org

  28. Adherence • A major determinant of degree and duration of viral suppression • Poor adherence associated with virologic failure • Optimal suppression requires 90-95% adherence • Suboptimal adherence is common

  29. Predictors of Inadequate Adherence • Regimen complexity and pill burden • Poor clinician-patient relationship • Active drug use or alcoholism • Unstable housing • Mental illness (especially depression) • Lack of patient education • Medication adverse effects • Fear of medication adverse effects

  30. Predictors of Inadequate Adherence • Age, race, sex, educational level, socioeconomic status, and a past history of alcoholism or drug use do NOT reliably predict suboptimal adherence. • Higher SES and education levels and lack of history of drug use do NOT reliably predict optimal adherence.

  31. Predictors of Good Adherence • Emotional and practical supports • Convenience of regimen • Understanding of the importance of adherence • Belief in efficacy of medications • Feeling comfortable taking medications in front of others • Keeping clinic appointments • Severity of symptoms or illness

  32. Improving Adherence • Establish readiness to start therapy • Provide education on medication dosing • Review potential side effects • Anticipate and treat side effects • Utilize educational aids including pictures, pillboxes, and calendars

  33. Improving Adherence • Simplify regimens, dosing, and food requirements • Engage family, friends • Utilize team approach with nurses, pharmacists, and peer counselors • Provide accessible, trusting health care team

  34. Case #2 • Older Haitian woman with OI • CD4 very low • Should we treat her? • Why? www.aidsetc.org

  35. Benefits of treating CA • Immunologic recovery • Likely somewhat blunted secondary to AIDS and low nadir count • Decreased risk for further OI • Decreased AIDS-related mortality • Except for tuberculous and cryptococcal meningitis, early ART reduces M/M especially if CD4 <50 www.aidsetc.org

  36. Case #3 • Young middle-aged homeless man • Irregular housing • Recent IDU relapse • CD4 low, but > 350 • Should we treat him? • Why? www.aidsetc.org

  37. Treating NC • Benefits • Decreased HIV morbidity • ? Decreased mortality • But NC is at high risk for nonadherence • How can we help him with that? www.aidsetc.org

  38. How do we construct an antiretroviral regimen for our patients? www.aidsetc.org

  39. Combination therapy • Allows effective, durable viral suppression • 3 standard combinations • 2 NRTI + 1 NNRTI • 2 NRTI + 1 PI • 2 NRTI + 1 II www.aidsetc.org

  40. Initial ART Regimens: DHHS Categories • Preferred • Randomized controlled trials show optimal efficacy and durability • Favorable tolerability and toxicity profiles • Alternative • Effective but have potential disadvantages • May be the preferred regimen for individual patients • Other • May be selected for some patients but are less satisfactory than preferred or alternative regimens www.aidsetc.org

  41. NRTI backbone • TDF/FTC preferred • What coinfection is also treated by this combination? • What cormorbidities might make this combination a suboptimal choice? • ABC/3TC alternative • What test should be performed prior to using abacavir? Why? www.aidsetc.org

  42. NNRTI options • EFV preferred • In what population should EFV NOT be used? • RPV alternative • Is RPV an optimal choice if VL > 100K? • What class of drugs is contraindicated in combination with RPV? www.aidsetc.org

  43. PI options • ATV/r and DRV/r preferred • What drug class must be used with caution in combination with ATV? • FPV/r and LPV/r alternative • Which comorbidities might make PI a suboptimal choice? • What drug classes interact with PIs? www.aidsetc.org

  44. II options • RAL preferred • EVG alternative • What comorbidity contraindicates EVG? www.aidsetc.org

  45. Websites to Access the Guidelines • http://www.aidsetc.org • http://aidsinfo.nih.gov www.aidsetc.org

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