![When to Start: Evolution of DHHS Treatment Initiation Guidelines Adapted from the Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. US Dept of Health and Human Services; 1998-2009. Factor Recommendation 1998 2001 2002 2004 2007 2009 AIDS Treat Treat Treat Treat Treat Treat CD4 count (cells/mm 3 ) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Viral load (copies/mL) >20,000 >55,000 > 100,000 No specific viral load No specific viral load Other factors ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)
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Ähnlich wie D1 Highly Active Antiretroviral Treatment (HAART) DHHS Guidelines 2009 Duffus
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D1 Highly Active Antiretroviral Treatment (HAART) DHHS Guidelines 2009 Duffus
- 1. Highly Active Antiretroviral Treatment (HAART) DHHS Guidelines 2009 Wayne Duffus, MD, PhD May 25 th 2010
- 5. ART in Patients >50 Years Old: ATHENA National Cohort Mean CD4 Count (cells/mm 3 ) Gras L, et al. J Acquir Immune Defic Syndr . 2007;45(2):183-192. Median CD4 Response in Patients ≥50 Years of Age at the Start of ART a a Solid lines represent control patient group (male patients <50 years of age at the start of ART); dashed lines represent patients ≥50 year of age at the start of ART. Years from Starting ART <50 cells/mm 3 50-200 cells/mm 3 200-350 cells/mm 3 350-500 cells/mm 3 ≥ 500 cells/mm 3 0 1 2 3 4 6 5 7 1100 1000 900 800 700 600 500 400 300 200 100 0
- 6. ART in Patients >50 Years Old: ATHENA National Cohort Gras L, et al. J Acquir Immune Defic Syndr . 2007;45(2):183-192. Median CD4 Response in Patients ≥50 Years of Age at the Start of ART a a Solid lines represent control patient group (male patients <50 years of age at the start of ART); dashed lines represent patients ≥50 year of age at the start of ART. Years from Starting ART 0 1 2 3 4 6 5 7 1100 1000 900 800 700 600 500 400 300 200 100 0 Mean CD4 Count (cells/mm 3 ) <50 cells/mm 3 50-200 cells/mm 3 200-350 cells/mm 3 350-500 cells/mm 3 ≥ 500 cells/mm 3
- 7. ART in Patients >50 Years Old: ATHENA National Cohort Gras L, et al. J Acquir Immune Defic Syndr . 2007;45(2):183-192. Median CD4 Response in Patients ≥50 Years of Age at the Start of ART a a Solid lines represent control patient group (male patients <50 years of age at the start of ART); dashed lines represent patients ≥50 year of age at the start of ART. Years from Starting ART 0 1 2 3 4 6 5 7 1100 1000 900 800 700 600 500 400 300 200 100 0 Mean CD4 Count (cells/mm 3 ) <50 cells/mm 3 50-200 cells/mm 3 200-350 cells/mm 3 350-500 cells/mm 3 ≥ 500 cells/mm 3
- 8. D:A:D Study: Lower CD4 Count and Detectable Viral Load Associated With Increased Risk of Death Smith C and D:A:D Study Group. 16 th CROI; 2009; Montreal. Abstract 145. HIV-RNA (log copies/mL) and ART Status Adjusted Rate Ratio (95% Cl) CD4 CD4 and HIV-RNA Status Overall AIDS Liver CVD Non-AIDS Malignancies Per 100 <2.6 on >2.6 on <4 off 4-5 off >5 off 0.1 0.5 1 5 10
- 13. Association Between Current CD4 Cell Count and Non-AIDS Complications Phillips A et al. 15 th CROI; 2008; Boston. Abstract 8. Is Lower Current CD4 Cell Count Significantly Associated With Increased Risk of non-AIDS Events? Study Non-AIDS malignancies Renal disease/death CVD events/death Liver disease/ death FIRST Yes Yes Trend, NS No D:A:D Yes Yes Trend, NS Yes CASCADE Yes NA Yes Yes SMART Trend, NS Trend, NS Trend, NS Yes
- 14. ART-CC: Prognosis Based on CD4 Count at Initiation of ART Sterne J et al. CROI 2009. Abstract 72LB. Graphic reproduced with permission for educational use only. Sterne J et al. Lancet . 2009;373(9672):1352-63. CD4 Threshold a Adjusted for lead-time and unobserved events. 0.5 1.0 2.0 4.0 500 400 300 100 HR for AIDS or Death a 200 0 Comparison (CD4 cells/mm 3 ) HR a (95% CI) 1-100 vs 101-200 3.35 (2.99-3.75) 101-200 vs 201-300 2.21 (1.91-2.56) 201-300 vs 301-400 1.34 (1.12-1.61) 251-350 vs 351-450 1.28 (1.04-1.57) 351-450 vs 451-550 0.99 (0.76-1.29)
- 27. Drug Resistance Testing: Recommendations To assist in selecting active drugs for a new regimen. Suboptimal suppression of viral load after starting ART Transmitted drug-resistant virus is common in some areas; is more likely to be detected earlier in the course of HIV infection. If treatment is deferred, consider repeat testing at time of ART initiation. Genotype preferred. Chronic HIV infection, at entry into care COMMENT RECOMMENDED To determine if resistant virus was transmitted; guide treatment decisions. If treatment is deferred, consider repeat testing at time of ART initiation. Genotype preferred. Acute HIV infection, regardless of whether treatment is to be started
- 28. Drug Resistance Testing: Recommendations (2) To assist in selecting active drugs for a new regimen. Genotype preferred if patient on 1st or 2nd regimen; add phenotype if known or suspected complex drug resistance pattern. If virologic failure on integrase inhibitor or fusion inhibitor, consider testing for resistance to these to determine whether to continue them. Coreceptor tropism assay if considering use of CCR5 antagonist. Virologic failure during ART COMMENT RECOMMENDED
- 29. Drug Resistance Testing: Recommendations (3) COMMENT RECOMMENDED Recommended before initiation of ART or prophylaxis. Recommended for all on ART with detectable HIV RNA levels. Genotype usually preferred; add phenotype if complex drug resistance mutation pattern. Pregnancy
- 30. Drug Resistance Testing: Recommendations (4) Resistance assays cannot consistently be performed if HIV RNA is low Plasma HIV RNA <500 copies/mL Resistance mutations may become minor species in the absence of selective drug pressure After discontinuation (>4 weeks) of ARVs NOT USUALLY RECOMMENDED COMMENT
- 39. Recommendations for Initiating ART (2) 50% of the Panel favors starting ART; 50% views ART as optional CD4 count >500 cells/µL , asymptomatic, without conditions listed above Recommendation Clinical Category or CD4 Count
- 46. DHHS Guidelines: Recommended Regimens for Treatment-Naïve Patients Preferred Regimens PI-based ATV + (3TC or FTC) + (AZT, d4T, ABC or ddI) or (TDF+RTV 100 mg/d) LPV/r + (3TC or FTC) + (d4T, ABC, TDF or ddI) FPV or FPV/r or IDV/r or NFV or SQV/r + (3TC or FTC) + (AZT, d4T, ABC, TDF or ddI) Alternative Regimens NNRTI-based EFV + (3TC or FTC) + (ABC, ddI or d4T) NVP + (3TC or FTC) + (AZT, d4T, ddI, ABC or TDF) EFV + (3TC or FTC) + (AZT or TDF) LPV/r + (3TC or FTC) + AZT 3 NRTI-based ABC + AZT + 3TC – only when a preferred or an alternative NNRTI- or PI-based regimen cannot or should not be used DHHS Guidelines for the Use of ARV Agents in HIV-1-Infected Adults and Adolescents; May 2006.
- 68. Patients Prefer Once-daily With Low Pill Burden 0 10 20 30 40 50 60 70 80 90 100 If you were to take a certain number of pills each day, how would you prefer them to be administered? All at once Divided and taken twice a day % patients preferring >8 pills 8 pills 6 pills 4 pills 3 pills 31% 69% 38% 62% 59% 41% 84% 16% 93% 7% Moyle G et al. Paper presented at: 6th International Congress on Drug Therapy in HIV Infection; Glasgow, Scotland; November 17-21, 2002. Poster 99.
Hinweis der Redaktion
- Antiretroviral therapy should be initiated in all patients with a history of an AIDS-defining illness or with CD4 count < 350 cells/mm3 (AI). • Antiretroviral therapy should also be initiated, regardless of CD4 count, in patients with the following conditions: pregnancy (AI), HIV-associated nephropathy (AII), and hepatitis B virus (HBV) coinfection when treatment of HBV is indicated (AIII). • Antiretroviral therapy is recommended for patients with CD4 counts between 350 and 500 cells/mm3. The Panel was divided on the strength of this recommendation: 55% of Panel members for strong recommendation (A) and 45% for moderate recommendation (B) (A/B-II). • For patients with CD4 counts >500 cells/mm3, 50% of Panel members favor starting antiretroviral therapy (B); the other 50% of members view treatment as optional (C) in this setting (B/C-III).
- Plasma HIV RNA (viral load) should be measured in all patients at baseline and on a regular basis thereafter, especially in patients who are on treatment, because viral load is the most important indicator of response to antiretroviral therapy (AI) . Analysis of 18 trials that included more than 5,000 participants with viral load monitoring showed a significant association between a decrease in plasma viremia and improved clinical outcome [9] . Thus, viral load testing serves as a surrogate marker for treatment response [10] and can be useful in predicting clinical progression [11-12] . The minimal change in viral load considered to be statistically significant (2 standard deviations) is a threefold, or a 0.5 log10 copies/mL change. One key goal of therapy is suppression of viral load to below the limits of detection (below 40–75 copies/mL by most commercially available assays). For most individuals who are adherent to their antiretroviral regimens and who do not harbor resistance mutations to the prescribed drugs, viral suppression is generally achieved in 12–24 weeks, even though it may take a longer time in some patients. Recommendations for the frequency of viral load monitoring are summarized below.
- Use of Resistance Assays in Clinical Practice (Table 4 ) No definitive prospective data exist to support using one type of resistance assay over another (i.e., genotypic vs. phenotypic) in different clinical situations. In most situations genotypic testing is preferred because of the faster turnaround time, lower cost, and enhanced sensitivity for detecting mixtures of wild-type and resistant virus. However, for patients with a complex treatment history, results derived from both assays might provide critical and complementary information to guide regimen changes. Use of Resistance Assays in Determining Initial Treatment Transmission of drug-resistant HIV strains is well documented and associated with suboptimal virologic response to initial antiretroviral therapy [16-19] . The likelihood that a patient will acquire drug-resistant virus is related to the prevalence of drug resistance in persons engaging in high-risk behaviors in the community. In the United States and Europe, recent studies suggest the risk that transmitted virus will be resistant to at least one antiretroviral drug is in the range of 6%–16% [20-25] , with 3%–5% of transmitted viruses exhibiting resistance to drugs from more than one class [24, 26] . If the decision is made to initiate therapy in a person with acute HIV infection, resistance testing at baseline will provide guidance in selecting a regimen to optimize virologic response. Therefore, resistance testing in this situation is recommended (AIII) using a genotypic assay. In the absence of therapy, resistant viruses may decline over time to less than the detection limit of standard resistance tests but may still increase the risk of treatment failure when therapy is eventually initiated. Therefore, if the decision is made to defer therapy, resistance testing during acute HIV infection should still be performed (AIII) . In this situation, the genotypic resistance test result might be kept on record for several years before it becomes clinically useful. Because it is possible for a patient to acquire drug-resistant virus (i.e., superinfection) between entry into care and initiation of antiretroviral therapy, repeat resistance testing at the time treatment is started should be considered (CIII) .
- Use of Resistance Assays in Clinical Practice (Table 4 ) No definitive prospective data exist to support using one type of resistance assay over another (i.e., genotypic vs. phenotypic) in different clinical situations. In most situations genotypic testing is preferred because of the faster turnaround time, lower cost, and enhanced sensitivity for detecting mixtures of wild-type and resistant virus. However, for patients with a complex treatment history, results derived from both assays might provide critical and complementary information to guide regimen changes. Use of Resistance Assays in Determining Initial Treatment Transmission of drug-resistant HIV strains is well documented and associated with suboptimal virologic response to initial antiretroviral therapy [16-19] . The likelihood that a patient will acquire drug-resistant virus is related to the prevalence of drug resistance in persons engaging in high-risk behaviors in the community. In the United States and Europe, recent studies suggest the risk that transmitted virus will be resistant to at least one antiretroviral drug is in the range of 6%–16% [20-25] , with 3%–5% of transmitted viruses exhibiting resistance to drugs from more than one class [24, 26] . If the decision is made to initiate therapy in a person with acute HIV infection, resistance testing at baseline will provide guidance in selecting a regimen to optimize virologic response. Therefore, resistance testing in this situation is recommended (AIII) using a genotypic assay. In the absence of therapy, resistant viruses may decline over time to less than the detection limit of standard resistance tests but may still increase the risk of treatment failure when therapy is eventually initiated. Therefore, if the decision is made to defer therapy, resistance testing during acute HIV infection should still be performed (AIII) . In this situation, the genotypic resistance test result might be kept on record for several years before it becomes clinically useful. Because it is possible for a patient to acquire drug-resistant virus (i.e., superinfection) between entry into care and initiation of antiretroviral therapy, repeat resistance testing at the time treatment is started should be considered (CIII) .
- Summary of Recommended Regimens The most extensively studied combination antiretroviral regimens for treatment-naïve patients generally consist of two NRTIs plus either one NNRTI or a PI (with or without ritonavir boosting). A list of Panel-recommended components for initial therapy in treatment-naïve patients can be found in Table 6 . Potential advantages and disadvantages of the components recommended as initial therapy for treatment-naïve patients are listed in Table 7 to guide prescribers in choosing the regimen best suited for an individual patient. A list of agents or components not recommended for initial treatment can be found in Table 8 . Some agents or components that are not recommended for use because of lack of potency or potential serious safety concerns are listed in Table 9