1 / 45

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

ghazi
Download Presentation

Antiretroviral Management of the HIV-Infected Patient

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related