Frequently Referenced Tables of DHHS Guidelines for the Treatment of HIV/AIDS. Spring 2006 Clinical Practice Edition

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1 Frequently Referenced Tables of DHHS Guidelines for the Treatment of HIV/AIDS Spring 2006 Clinical Practice Edition

2 Frequently Referenced Tables of DHHS Guidelines for the Treatment of HIV/AIDS Spring 2006 Clinical Practice Edition Acknowledgements This guide was developed and prepared by the following: Melissa Laurie Marshall Glesby, MD, PhD John Faragon, PharmD This project was funded with a grant from Abbott Laboratories This education guide is sponsored by the New York/New Jersey AIDS Education and Training Center (NY/NJ AETC). The NY/NJ AETC is funded by the Health Resources and Services Administration (HRSA) and is part of the National AIDS Education & Training Center Program, a network of 11 federally funded regional centers that conduct targeted multidisciplinary HIV/AIDS education and training programs for health care providers. Disclaimer: The data in this guide are intended for use by clinicians and other health care providers as guidance for antiretroviral management in patients with HIV/AIDS. Information on HIV is rapidly evolving and changing. These guidelines are for informational purposes only and cannot identify medical risks specific to an individual patient or recommend patient treatment. The absence of typographical errors is not guaranteed. These guidelines are not necessarily all-inclusive. Use of these guidelines indicates acknowledgement that neither NY/NJ AETC, nor the authors will be responsible for any loss or injury, sustained in connection with, or as a result of, the use of these guidelines. Users of this guide should consult other sources before prescribing medications or treatment. Data were compiled from the Department of Health and Human Services (DHHS) guidelines. Presented courtesy of the New York/New Jersey AETC at Columbia University Columbia 2006

3 TABLE 5 DHHS GUIDELINES, MAY 2006 ADULTS AND ADOLESCENTS INDICATIONS FOR INITIATING ANTIRETROVIRAL THERAPY FOR THE CHRONICALLY HIV-1 INFECTED PATIENT Clinical Category CD4+ Cell Count Plasma HIV RNA Recommendation AIDS-defining illness or Any Value Any Value Treat severe symptoms *(AI) Asymptomatic **(AI) Asymptomatic (BII) Asymptomatic (CII) Asymptomatic (DII) CD4 + T cells Any Value Treat < 200/mm 3 CD4 + T cells Any Value Treatment should be offered > 200/mm 3 but 350/mm 3 CD4 + T cells 100,000 Most clinicians recommend deferring therapy > 350/mm 3 CD4 + T cells < 100,000 Defer Therapy > 350/mm 3 TABLE 6 DHHS GUIDELINES, NOV 2005 PEDIATRIC INDICATIONS FOR INITIATION OF ANTIRETROVIRAL THERAPY IN CHILDREN <12 MONTHS OF AGE INFECTED WITH HIV Clinical Category CD4+ Cell Percentage Plasma HIV RNA Copy Number 1 Recommendation Symptomatic OR < 25% Any Value Treat (Clinical category A, B, or C) (Immune Category 2 or 3) Asymptomatic AND (Clinical category N) 25% (Immune Category 1) Any Value Consider Treatment 2 TABLE 7 DHHS GUIDELINES, NOV 2005 PEDIATRIC AIDS OR (Clinical category C) INDICATIONS FOR INITIATION OF ANTIRETROVIRAL THERAPY IN CHILDREN 1 YEAR OF AGE INFECTED WITH HIV < 15% (Immune Category 3) Any Value Treat Mild-Moderate Symptoms OR (Clinical category A or B) 15-25% 1 OR (Immune Category 2) 100,000 copies/ml 2 Consider Treatment Asymptomatic AND (Clinical category N) > 25% AND (Immune Category 1) < 100,000 copies/ml 2 Many experts would defer therapy and closely monitor clinical, immune, and viral parameters Refer to Table 5, 6 and 7 of DHHS Guidelines for details. (AI,BII,CII,DII For clarification refer to reference page for more information.)

4 TABLE 6 DHHS GUIDELINES, MAY 2006 ADULTS AND ADOLESCENTS ANTIRETROVIRAL REGIMENS RECOMMENDED FOR TREATMENT OF HIV-1 INFECTION IN ANTIRETROVIRAL NAÏVE PATIENTS Preferred Regimens NNRTI-based REGIMENS efavirenz + (lamivudine or emtricitabine) + (zidovudine or tenofovir DF ) (AII) [note: efavirenz is not recommended for use in 1st trimester of pregnancy or in women with high pregnancy potential*] # OF PILLS 2-3 PI-based lopinavir/ritonavir (co-formulation) + (lamivudine or emtricitabine) + zidovudine (AII) 6-7 Alternative Regimens NNRTI-based PI-based efavirenz + (lamivudine or emtricitabine) + (abacavir or didanosine or stavudine)(bii) [note: efavirenz is not recommended for use in 1st trimester of pregnancy or in women with high pregnancy potential*] nevirapine + (lamivudine or emtricitabine) + (zidovudine or stavudine or didanosine or abacavir or tenofovir) (BII) [Note: High incidence (11%) of symptomatic hepatic events observed in women with prenevirapine CD4+ T cell count > 250 cells/mm 3 and men with CD4 > 400 cells/mm 3 (6.3%). Nevirapine should not be initiated in these patients unless the benefits clearly outweight the risks.] atazanavir + (lamivudine or emtricitabine) + (zidovudine or stavudine or abacavir or didanosine) or (tenofovir + ritonavir 100mg/d) (BII) fosamprenavir + (lamivudine or emtricitabine) + (zidovudine or stavudine or abacavir or tenofovir or didanosine) (BII) fosamprenavir/ritonavir + (lamivudine or emtricitabine) + (zidovudine or stavudine or abacavir or tenofovir or didanosine) (BII) indinavir/ritonavir +(lamivudine or emtricitabine)+(zidovudine or stavudine or abacavir or tenofovir or didanosine) (BII) lopinavir/ritonavir + (lamivudine or emtricitabine) + (stavudine or abacavir or tenofovir or didanosine) (BII) nelfinavir + (lamivudine or emtricitabine) + (zidovudine or stavudine or abacavir or tenofovir or didanosine (CII) saquinavir (sgc, hgc or tablets) ø /ritonavir + (lamivudine or emtricitabine) + (zidovudine or stavudine or abacavir or tenofovir or didanosine) (BII) NRTI-based abacavir + zidovudine + lamivudine - only when a preferred or an alternative NNRTIor a PI-based regimen cannot or should not be used (CII) 2 *Women with child bearing potential implies women who want to conceive or those who are not using effective contraception. (AII,BII,CII For clarification refer to reference page for more information.) Refer to Table 6 of the DHHS Guidelines for details.

5 TABLE 10 DHHS GUIDELINES, MAY 2006 ADULTS AND ADOLESCENTS Monotherapy (EII) 2-NRTI regimens (EII) ANTIRETROVIRAL REGIMENS OR COMPONENTS THAT SHOULD NOT BE OFFERED AT ANY TIME ANTIRETROVIRAL REGIMENS NOT RECOMMENDED RATIONALE Rapid development of resistance Inferior antiretroviral activity when compared to combination with three or more antiretrovirals Rapid development of resistance Inferior antiretroviral activity when compared to combination with three or more antiretrovirals High rate of early virologic non-response seen when this triple NRTI combination was used as initial regimen in treatment naïve patients High rate of early virologic non-response seen when this triple NRTI combination was used as initial regimen in treatment-naïve patients Abacavir + tenofovir + lamivudine (or emtricitabine) as a triple-nrti regimen (EII) Tenofovir + didanosine + lamivudine (or emtricitabine) as a triple-nrti regimen (EII) ANTIRETROVIRAL COMPONENTS NOT RECOMMENDED AS PART OF ANTIRETROVIRAL REGIMEN Amprenavir oral solution (EIII) in: Oral liquid contains large amount of excipient propylene glycol, which may be toxic in pregnant women; children < 4 yr old; patients at risk patients with renal or hepatic failure; & patients on metronidazole or disulfiram EXCEPTION Pregnant women with HIV-RNA < 1,000 c/ml for the prevention of perinatal HIV transmission For patients currently on this treatment some clinicians may continue if virologic goals are achieved (DII) Amprenavir + fosamprenavir (EII) Amprenavir is the active antiviral for both drugs, combined use has no benefit and may increase toxicities Amprenavir oral solution + ritonavir oral solution (EIII) The large amount of propylene glycol used as a vehicle in amprenavir oral solution may compete with ethanol (the vehicle in oral ritonavir solution) for the same metabolic pathway for elimination. This may lead to accumulation of either one of the vehicles. Atazanavir + indinavir (EIII) Potential additive hyperbilirubinemia Didanosine + stavudine (EIII) High incidence of toxicities peripheral neuropathy, pancreatitis, and hyperlactatemia Reports of serious, even fatal, cases of lactic acidosis with hepatic steatosis with or without pancreatitis in pregnant women* When no other antiretroviral options are available and potential benefits outweigh the risks * (DIII) Didanosine + zalcitabine (EIII) Efavirenz in 1st trimester of pregnancy or with significant child-bearing potential* (EIII) Emtricitabine + lamivudine (EIII) Additive peripheral neuropathy Teratogenic in nonhuman primate Similar resistance profile No potential benefit When no other antiretroviral options are available and potential benefits outweigh the risks * (DIII) Lamivudine + Zalcitabine (EIII) In vitro antagonism Nevirapine initiation in women with CD4 Higher incidents of symptomatic (incl. serious or fatal) hepatitic events in these patient groups Only if the benefits clearly outweigh the risks >250 cells/mm 3 or men with CD4 >400 cells/mm 3 (DI) Saquinavir hard gel capsule (Invirase) as single protease inhibitor (EIII) Poor oral bioavailability (4%) Inferior antiretroviral activity when compared to other protease inhibitors Stavudine + zalcitabine (EIII) Additive peripheral neuropathy Stavudine + zidovudine (EII) Antagonistic effect on HIV-1 and not for HIV treatment for the mother. * Refer to Table 10 of the DHHS Guidelines for details. (DI,DII,DlII,EII,EIII For clarification refer to reference page for more information.)

6 TABLE 22a DHHS GUIDELINES, MAY 2006 ADULTS AND ADOLESCENTS DOSING RECOMMENDATIONS FOR PI COMBINATION THERAPY Drug Affected Fos-amprenavir Atazanavir Lopinavir/Ritonavir Nelfinavir PROTEASE INHIBITORS Fos-amprenavir (f-apv) Levels: f-apv/atv 1400/400 qd, ATV AUC Should not be coadministered: increased 33% & Cmin 57%. f-apv AUC 78% & rate of adverse events seen and doses are Cmin 283%. f-apv/r 700/100 mg bid + not established ATV 300 mg qd, ATV AUC 22% & Cmax 24%; f-apv was unchanged Dose: insufficient data Indinavir (IDV) Levels: APV AUC increase 33% Dose: not established Coadministration of these agents is not recommended because of potential for additive hyperbilirubinema Dose: IDV 600 mg bid Levels: IDV increase 50%; NFV increase 80% Dose: Limited data for IDV1200 mg bid + NFV 1250 mg bid Lopinavir/Ritonavir (LPV/r) Levels: With ATV 300 qd + LPV/r 400/100 bid, ATV Cmin 45%; ATV AUC and Cmax were unchanged LPV PK similar to historic data Nelfinavir (NFV) Levels: APV AUC increase 1.5-fold Dose: insufficient data Levels: With LPV capsules, LPV 27%; NFV 25% Dose: No data with LPV/r tablets. No dosing recommendation Ritonavir (RTV) Dose: ATV 300 mg qd + RTV 100 mg qd Lopinavir is co-formulated with ritonavir as Kaletra Additional RTV generally not recommended Levels: RTV no effect; NFV increase 1.5 times Dose: not established Saquinavir (SQV) Levels: APV AUC decrease 32% Dose: insufficient data Levels: SQV AUC 60% with SQV/ATV/RTV 1600/300/100 qd, compared with SQV/ RTV 1600/100 qd Dose: no recommendations can be made Dose: SQV 1000 mg bid, LPV/r standard Dose: Standard NFV; Fortovase 800 mg tid or 1200 mg bid * Several drug interaction studies have been completed with saquinavir given as Invirase or Fortovase. Results from studies conducted with Invirase may not be applicable to Fortovase. Refer to table 22a of the DHHS Guidelines for details and complete levels information. (*For clarification refer to reference page for more information.)

7 TABLE 22a, Cont d DHHS GUIDELINES, MAY 2006 ADULTS AND ADOLESCENTS DOSING RECOMMENDATIONS FOR PI COMBINATION THERAPY Drug Affected Ritonavir Saquinavir * Tipranavir PROTEASE INHIBITORS Fos-amprenavir (f-apv) Dose: (f-apv 1,400 mg + RTV 200 mg) qd; or (f-apv 700 mg + RTV 100 mg) bid Levels: APV AUC decrease 32% Dose: insufficient data No data with f-apv, but a in AUC is expected Should not be co-administered as doses are not established Indinavir (IDV) Dose: 400/400 mg or 800/100 mg or 800/200 mg IDV/RTV bid Caution: renal events may be increased with higher IDV concentrations Levels: IDV no effect SQV increase 4-7 times Dose: insufficient data Should not be co-administered as doses are not established Lopinavir/Ritonavir (LPV/r) Additional RTV generally not recommended LPV AUC and Cmin 55 and 70% Should not be co-administered as doses are not established Nelfinavir (NFV) Should not be co-administered as doses are not established Ritonavir (RTV) Dose: 1000/100 mg SQV sgc or hgc/rtv bid or 400/400 mg bid Levels: TPV AUC 11-fold Dose: TPV 500 mg bid + RTV 200 mg bid Saquinavir (SQV) SQV AUC and Cmin 76 and 82% when given as SQV/r 600/100 BID with TPV/r Should not be co-administered as doses are not established * Several drug interaction studies have been completed with saquinavir given as Invirase or Fortovase. Results from studies conducted with Invirase may not be applicable to Fortovase. Study conducted with Fortovase. Refer to table 22a of the DHHS Guidelines for details and complete levels information. (*For clarification refer to reference page for more information.)

8 TABLE 22b DHHS GUIDELINES, MAY 2006 DOSING RECOMMENDATIONS FOR PI/NNRTI COMBINATION THERAPY ADULTS AND ADOLESCENTS Drug Affected Delavirdine Efavirenz Nevirapine Atazanavir (ATV) Dose: ATV RTV 100 mg each qd with food. ATV concentrations similar to unboosted ATV; if desired ATV concentrations not achieved, may need to increase the dose of ATV/r but insufficient information for specific recommendation. EFV dose standard A decrease in ATV levels is expected. Co-administration is not recommended. Effect of NVP on ATV/RTV combination unknown; if used, consider monitoring ATV level. Fosamprenavir (f-apv) Presumably similar PK affects as APV: APV AUC increase 130%, and DLV AUC decrease 61% Dose: Co-administration not recommended Dose: (f-apv 1,400 mg + RTV 300 mg) qd; or (f-apv 700 mg + RTV 100 mg) bid Indinavir (IDV) Dose: IDV 600mg q8h DLV standard Dose: IDV 1000 mg q8h or consider IDV/RTV, EFV standard Dose: IDV 1000 mg q8h or consider IDV/RTV, NVP standard Lopinavir/ Ritonavir (LPV/RTV) Nelfinavir (NFV) Levels: LPV levels expected to increase Dose: Insufficient data Levels: NFV increase 2 times; DLV decrease 50% Dose: No data Dose: LPV/r tablets 600/150 mg bid, when used in combination with EFV in tx-experienced patients EFV standard Dose: Standard Dose: LPV/r tablets 600/150 mg bid, when used in combination with NVP in tx-experienced patients NVP standard Dose: Standard Ritonavir (RTV) Levels: RTV increased 70%. DLV no effect Dose: Not established Dose: Standard Dose: Standard Saquinavir (SQV) Dose: Fortovase 800 mg tid, DLV standard (monitor transaminase levels) Dose: Consider SQV/RTV 400/400 mg bid Dose: Consider SQV-sgc/RTV 400/400 mg or 1000/100 bid or SQV-hgc/RTV 1000/100 mg bid Tipranavir Dose: No dose adjustments necessary Levels: No data of effect of NVP on TPV/r PK. NVP PK unchanged. a a Study conducted with TPV/r dose(s) other than FDA-approved dose of 500/200 mg bid Refer to TABLE 22 b of the DHHS Guidelines for details.

9 TABLE 11 DHHS GUIDELINES, NOV 2005 PEDIATRIC Strongly Recommended: Two NRTIs 1 plus Lopinavir/ritonavir or Nelfinavir or Ritonavir Alternative Recommendation: Two NRTIs 1 plus Amprenavir (children 4 years old) 2 or Indinavir Strongly Recommended: Children > 3 years: Two NRTIs 1 plus Efavirenz 3 (with or without Nelfinavir) Children 3 years or who can t swallow capsules: Two NRTIs 1 plus Nevirapine 3 Alternative Recommendation: RECOMMENDED ANTIRETROVIRAL REGIMENS FOR INITIAL THERAPY FOR HIV INFECTION IN CHILDREN PROTEASE INHIBITOR-BASED REGIMENS NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR-BASED REGIMENS Two NRTIs 1 plus Nevirapine 3 (children >3 years) Strongly Recommended: Alternative Recommendation: Use in Special Circumstances: NUCLEOSIDE ANALOGUE-BASED REGIMENS None Zidovudine plus Lamivudine plus Abacavir Two NRTIs 1 REGIMENS THAT ARE NOT RECOMMENDED Monotherapy 4 Certain two NRTI combinations 1 Two NRTIs plus Saquinavir soft or hard gel capsule as a sole protease inhibitor 5 INSUFFICIENT DATA TO RECOMMEND Two NRTIs 1 plus Delavirdine Dual protease inhibitors, including saquinavir soft or hard gel capsule with low dose ritonavir, with the exception of lopinavir/ritonavir 4 NRTI plus NNRTI plus protease inhibitor 6 Tenofovir-containing regimens Enfuvirtide (T-20)-containing regimens Emtricitabine (FTC)-containing regimens Atazanavir-containing regimens Fosamprenavir-containing regimens Tipranavir-containing regimens (1-6 For clarification refer to reference page for more information.) Refer to Table 11 of the DHHS Guidelines for details.

10 REFERENCES TABLE 5 DHHS Guidelines, May 2006 Adults and Adolescents: The optimal time to initiate therapy is unknown among persons with asymptomatic disease and CD4+ T cell count of > 200 cells/mm 3. This table provides general guidance rather than absolute recommendations for an individual patient. All decisions regarding initiating therapy should be made on the basis of prognosis as determined by the CD4+ T cell count and level of plasma HIV RNA indicated in Table 4 of the DHHS Guidelines, the potential benefits and risks of therapy, and the willingness of the patient to accept therapy. * AIDS-defining illness per Centers for Disease Control, Severe symptoms include unexplained fever or diarrhea >2-4 weeks, oral candidiasis, or >10% unexplained weight loss. ** Clinical benefit has been demonstrated in controlled trials only for patients with CD4+ T cells <200/mm 3, however, the majority of clinicians would offer therapy at a CD4 + T cell threshold <350/mm 3. A collaborative analysis of data from 13 cohort studies from Europe and North America found that lower CD4 count, higher HIV viral load, injection drug use, and age over 50 were all predictors of progression to AIDS or death in antiretroviral naïve patients beginning combination antiretroviral therapy. These data indicate that the prognosis is better for patients who initiate therapy at >200 cells/mm 3, but risk after initiation of therapy does not vary considerably at >200 cells/mm 3. (For additional information, see When to Treat - Indications for Antiretroviral Therapy ) TABLE 6 DHHS Guidelines, November 2005 Pediatric: This table provides general guidance rather than absolute recommendations for an individual patient. Factors to be considered in decisions about initiation of therapy include the risk of disease progression as determined by CD4+ percentage; the potential benefits and risks of therapy; and the ability of the caregiver to adhere to administration of the therapeutic regimen. Issues associated with adherence should be fully assessed, discussed, and addressed with the caregivers for the HIV-infected infant before the decision to initiate therapy is made. 1 Plasma HIV RNA levels are higher in HIV-infected infants than older infected children and adults. Because overall levels are HIV RNA levels are high and overlap between infants who have and those who do not have rapid disease progression, HIV RNA levels may be hard to read in infants <12 months of age. 2 Because HIV progresses more rapidly in infants than older children and adults, some experts would treat all HIV-infected infants <6 months or <12 months of age, regardless of clinical, immunologic or virologic parameters. TABLE 7 DHHS Guidelines, November 2005 Pediatric: This table provides general guidance rather than absolute recommendations for an individual patient. Factors to be considered in decisions about initiation of therapy include the risk of disease progression as determined by CD4+ percentage; the potential benefits and risks of therapy; and the ability of the caregiver to adhere to administration of the therapeutic regimen. Issues associated with adherence should be fully assessed, discussed, and addressed with the caregivers for the HIV-infected infant before the decision to initiate therapy is made. 1 Many experts would initiate therapy if CD4+ cell percentage is between 15 to 20%, and defer therapy with increased monitoring frequency in children with CD4+ cell percentage 21% to 25%. 2 There is controversy among pediatric HIV experts regarding the plasma HIV RNAthreshold warranting consideration of therapy in children in the absence of clinical or immune abnormalities; some experts would consider initiation of therapy in asymptomatic children if plasma HIV RNA levels were between 50,000 to100,000 copies/ml. TABLE 6 DHHS Guidelines, May 2006 Adults and Adolescents: Regimens should be individualized based on the advantages and disadvantages of each combination such as pill burden, dosing frequency, toxicities, drug-drug interaction potential, co-morbid conditions, and level of plasma HIV-RNA. Clinicians should refer to Table 7 of the DHHS Guidelines to review the pros and cons of different components of a regimen and to Tables of the DHHS Guidelines for adverse effects and dosages of individual antiretroviral agents. Preferred regimens are in bold type; regimens are designated as "preferred" for use in treatment naïve patients when clinical trial data suggest optimal and durable efficacy with acceptable tolerability and ease of use. Alternative regimens are those where clinical trial data show efficacy, but it is considered alternative due to disadvantages compared to the preferred agent, such as antiviral activity, durability, tolerability, drug interaction potential, or ease of use. In some cases, based on individual patient characteristics, a regimen listed as alternative in this table may actually be the preferred regimen for a selected patient. Clinicians initiating antiretroviral regimens in the HIV-1-infected pregnant patient should refer to "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" at: aidsinfo.nih.gov/guidelines/. * Women with child bearing potential implies women who want to conceive or those who are not using effective contraception. Low-dose ( mg) ritonavir per day. ø sgc = soft gel capsule; hgc = hard gel capsule. TABLE 10 DHHS Guidelines, May 2006 Adults and Adolescents: * When constructing an antiretroviral regimen for an HIV-infected pregnant woman, please consult "Public Health Service Task Force Recommendations for the 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" in: aidsinfo.nih.gov/guidelines/. References cont d on next page

11 REFERENCES cont d TABLE 22a DHHS Guidelines, May 2006 Adults and Adolescents: * Several drug interaction studies have been completed with saquinavir given as Invirase or Fortovase. Results from studies conducted with Invirase may not be applicable to Fortovase. TABLE 22b DHHS Guidelines, May 2006 Adults and Adolescents. TABLE 11 DHHS Guidelines, November 2005 Pediatric: 1 Dual NRTI combination recommendations: Strongly Recommended choices: Zidovudine plus didanosine or lamivudine; or stavudine plus lamivudine Alternative Choices: Abacavir plus zidovudine or lamivudine; or didanosine plus lamivudine Use in Special Circumstances: Stavudine plus didanosine; or zalcitabine plus zidovudine Insufficient Data: Tenofovir- or emtricitabine-containing regimens Not Recommended: Zalcitabine plus didanosine, stavudine, or lamivudine; or zidovudine plus stavudine; or emtricitabine plus lamivudine 2 Amprenavir should not be administered to children under age 4 years due to the propylene glycol and vitamin E content of the oral liquid preparation and lack of pharmacokinetic data in this age group (see Appendix and Supplemental I). 3 Efavirenz is currently available only in capsule form, although a liquid formulation is currently under study to determine appropriate dosage in HIV-infected children under age 3 years; nevirapine would be the preferred NNRTI for children under age 3 years or who require a liquid formulation. 4 Except for zidovudine chemoprophylaxis administered to HIV-exposed infants during the first 6 weeks of life to prevent perinatal HIV transmission; if an infant is confirmed as HIV-infected while receiving zidovudine prophylaxis, therapy should either be discontinued or changed to a combination antiretroviral drug regimen. 5 With the exception of lopinavir/ritonavir, data on the pharmacokinetics and safety of dual protease inhibitor combinations (e.g., low dose ritonavir pharmacologic boosting of saquinavir, indinavir, or nelfinavir) are limited, use of dual protease inhibitors as a component of initial therapy is not recommended, although such regimens may have utility as secondary treatment regimens for children who have failed initial therapy. Saquinavir soft and hard gel capsule require low dose ritonavir boosting to achieve adequate levels in children, but pharmacokinetic data on appropriate dosing are not yet available. 6 With the exception of efavirenz plus nelfinavir plus 1 or 2 NRTIs, which has been studied in HIV-infected children and shown to have virologic and immunologic efficacy in a clinical trial. NRTI: Nucleoside analogue reverse transcriptase inhibitor NNRTI: Non-nucleoside analogue reverse transcriptase inhibitor (AI,AII,BII,CII,DI,DII,DlII,EII,EIII) Rating Scheme for Clinical Practice Recommendations: A. Strong, B. Moderate, C. Optional, D. Should usually not be offered, E. Should never be offered, I At least one randomized trial with clinical results, II Clinical trials with laboratory results, III Expert opinion, DHHS Guidelines, October 6,

12 RESOURCES The National AETC Program also includes the following services: National HIV/AIDS Clinicians Consultation Center: Offering treating clinicians current HIV clinical and drug information and individualized, expert case consultation. Post-Exposure Prophylaxis 24 Hour Hotline: HIV-4911 Providing consultation for occupational exposures. Perinatal Hotline: Providing consultation for perinatal exposure and treatment. AETC HIV/AIDS National Resource Center: aids-etc.org Providing resources (including curricula and lecture slide sets) on HIV disease treatment, education and data. For further information, please visit one of the following websites: aidsinfo.nih.gov hivguidelines.org To obtain information about drug treatment and harm reduction contact: samhasa.gov or nattc.org (for treatment information) harmreduction.org (for harm reduction information)