0
June 25, 1997, Vol 277, No. 24 >
ARTICLE | June 25, 1997

Antiretroviral Therapy for HIV Infection in 1997: Title and subTitle BreakUpdated Recommendations of the International AIDS Society—USA Panel FREE

Charles C. J. Carpenter, MD; Margaret A. Fischl, MD; Scott M. Hammer, MD; Martin S. Hirsch, MD; Donna M. Jacobsen; David A. Katzenstein, MD; Julio S. G. Montaner, MD; Douglas D. Richman, MD; Michael S. Saag, MD; Robert T. Schooley, MD; Melanie A. Thompson, MD; Stefano Vella, MD; Patrick G. Yeni, MD; Paul A. Volberding, MD
[+] Author Affiliations

Financial disclosures for authors named appear at the end of this article.

Corresponding author: Charles C. J. Carpenter, MD, Brown University School of Medicine, The Miriam Hospital, 164 Summit Ave, Providence, RI 02906.

Reprints: International AIDS Society—USA, 353 Kearny St, San Francisco, CA 94108.


JAMA. 1997;277(24):1962-1969. doi:10.1001/jama.1997.03540480062040
Text Size: A A A
Published online
Article
References

Objective.  —To provide current recommendations for antiretroviral therapy for human immunodeficiency virus (HIV) disease.

Participants.  —The original International AIDS Society—USA 13-member panel representing international expertise in antiretroviral research and care of patients with HIV infection.

Evidence.  —The following were considered: Newly available clinical and basic science study results, including phase 3 controlled trials; clinical, virological, and immunologic end-point data; interim analyses of studies presented at national and international research conferences; studies of HIV pathophysiology; and expert opinions of panel members. Recommendations were limited to the drugs available in mid 1997.

Process.  —The full panel met on a regular basis (July 1996, September 1996, November 1996, January 1997, and April 1997) since the publication of its initial recommendations in mid 1996 to review new research reports and interim results. The panel discussed whether and how new information changed its initial recommendations. The recommendations contained herein were determined by group consensus.

Conclusions.  —New data have provided a stronger rationale for earlier initiation of more aggressive therapy than previously recommended and reinforce the importance of careful selection of initial drug regimen for each patient for optimal long-term clinical benefit and adherence. The plasma viral load is a crucial element of clinical management for assessing prognosis and the effectiveness of therapy, and such testing must be done properly. Treatment failure is most readily indicated by a rising plasma HIV RNA level and should be confirmed prior to a change of treatment. Therapeutic approaches must be updated as new data, particularly on the long-term clinical effect of aggressive antiretroviral treatment, continue to emerge.

REFERENCES

1 +
Carpenter CCJ, Fischl MA,  Hammer SM, et al, for the International AIDS Society—USA. Antiretroviral therapy for HIV infection in 1996: recommendations of an international panel . JAMA . 1996;;276:146-154.
2 +
Pantaleo G, Graziosi C, Demarest JF, et al.  HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease . Nature . 1993;;362:355-358.
3 +
Embretson J, Zupancic M, Ribas JL, et al.  Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS . Nature . 1993;;362:359-362.
4 +
Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M.  Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection . Nature . 1995;;373:123-126.
5 +
Wei X, Ghosh SK, Taylor ME, et al.  Viral dynamics in human immunodeficiency virus type 1 . Nature . 1995;;373:117-122.
6 +
Perelson AS, Neuman AU, Markowitz M, Leonard JM, Ho DD.  HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span and viral generation time . Science . 1996;;271:1582-1586.
7 +
Cohen OJ, Pantaleo G, Holodniy M, et al.  Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissues . Proc Natl Acad Sci USA . 1995;;92:6017-6021.
8 +
Pantaleo G, Menzo S, Vaccarezza M, et al.  Studies in subjects with long-term nonprogressive human immunodeficiency virus infection . N Engl J Med . 1995;;332:209-216.
9 +
Haase AT, Henry K, Zupancic M, et al.  Quantitative image analysis of HIV-1 infection in lymphoid tissue . Science . 1996;;274:985-989.
10 +
Boswell SL, Mayer KH, Goldstein RS, Tucker L, Xu C, Anderson D.  The effect of HIV protease inhibitors on seminal proviral DNA . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-26, 1997;; Washington, DC. Abstract 202.
11 +
Pialoux G, Fournier S, Moulignier A, Poveda JD, Clavel F, Dupont B.  Central nervous system as sanctuary of HIV-1 in a patient treated with AZT + 3TC + indinavir . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-26, 1997;; Washington, DC. Abstract 233.
12 +
Gupta P, Mellors J, Kingsley L, et al.  High viral load in semen of HIV-1 infected men at all stages of disease and its reduction by antiretroviral therapy . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-26, 1997;; Washington, DC. Abstract 726.
13 +
Lennox J, Ellerbrock T, Palmore M, et al.  Effect of antiretroviral therapy on vaginal HIV RNA level . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-26, 1997;; Washington, DC. Abstract 727.
14 +
Mellors JW, Kinsley LA, Rinaldo CR, et al.  Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion . Ann Intern Med . 1995;;122:573-579.
15 +
Katzenstein DA, Hammer SM, Hughes MD, et al, for the AIDS Clinical Trials Group Study 175 Virology Study Team.  The relation of virologic and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells/μL . N Engl J Med . 1996;;335:1091-1098.
16 +
O'Brien TR, Blattner WA, Waters D, et al.  Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study . JAMA . 1996;;276:105-110.
17 +
Mellors JW, Kingsley L, Gupta P, et al.  Prognostic value of plasma HIV-1 RNA quantification in seropositive adult men . In: Program and abstracts of the XI International Conference on AIDS ; July 7-12, 1996;; Vancouver, British Columbia. Abstract We.B.410.
18 +
Hammer SM, Katzenstein DA, Hughes MD, et al, for the AIDS Clinical Trials Group Study 175 Study Team.  A trial comparing nucleoside monotherapy with combination therapy in HIV-infected adults with CD4 cell counts from 200 to 500/μL . N Engl J Med . 1996;;335:1081-1090.
19 +
Coombs RW, Welles SL, Hooper C, et al.  Association of plasma human immunodeficiency virus type-1 RNA level with risk of clinical progression in patients with advanced infection . J Infect Dis . 1996;;174:704-712.
20 +
Welles SL, Jackson JB, Yen-Lieberman B.  Prognostic value of plasma HIV-1 RNA levels in patients with advanced HIV-1 disease and with little or no zidovudine therapy . J Infect Dis . 1996;;174:696-703.
21 +
O'Brien WA, Hartigan PM, Martin D, et al.  Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of progression to AIDS: Veterans Affairs Cooperative Study Group on AIDS . N Engl J Med . 1996;;334:426-431.
22 +
Saag MS, Holodniy M, Kuritzkes DR, et al.  HIV viral load markers in clinical practice . Nat Med . 1996;; 2:625-629.
23 +
Brichacek B, Swindells S,Jannoff E, Pirrucello S, Stevenson M.  Increased plasma human immunodeficiency virus type 1 burden following antigenic challenge with vaccine . J Infect Dis . 1996;;174:1191-1199.
24 +
Staprans SL, Hamilton BL, Follansbee SE, et al.  Activation of virus replication after vaccination of HIV-1 infected individuals . J Exp Med . 1995;;182:1727-1737.
25 +
O'Brien WA, Grovit-Ferbas K, Namazi A, et al.  Human immunodeficiency virus-type 1 replication can be increased in peripheral blood of seropositive patients after influenza vaccination . Blood . 1995;;86:1082-1089.
26 +
De Gruttola V, Fleming T, Lin DY, Coombs R.  Perspective: validating surrogate markers—are we being naive? J Infect Dis . 1997;;175:237-245.
27 +
Mellors JW.  Prognosis in HIV-1 infection predicted by the quantity of virus in plasma . Science . 1996;;272:1167-1170.
28 +
Mellors JW, Munoz AM, Giorgi VJ, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med. In press.
29 +
Dean M, Carrington M, Winkler C, et al.  Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene . Science . 1996;;273:1856-1861.
30 +
Samson M, Libert F, Doranz BJ, et al.  Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene . Nature . 1996;;382:722-725.
31 +
Wong JK, Gunthard HF, Havlir DV, et al.  Reduction of HIV in blood and lymph nodes after potent antiretroviral therapy . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-26, 1997;; Washington, DC. Abstract LB10.
32 +
Gulick RM, Mellors JW, Havlir D, et al.  Potent and sustained antiretroviral activity of indinavir (IDV), zidovudine (ZDV), and lamivudine (3TC) . In: Program and abstracts of the XI International Conference on AIDS ; July 7-12, 1996;; Vancouver, British Columbia. Abstract Th.B.931.
33 +
Hirsch MS, Meibohm A, Rawlins S, Leavitt R, for the Protocol 039 (Indinavir) Study Group.  Indinavir (IDV) in combination with zidovudine (ZDV) and lamivudine (3TC) in ZDV-experienced patients with CD4+ cell counts ≤50 cells/mm3 . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-27, 1997;; Washington, DC. Abstract LB7.
34 +
Powderly WG, Sension M, Conant M, Stein A, Clendeninn N.  The efficacy of Viracept (nelfinavir mesylate, NFV) in pivotal phase I/II double-blind randomized controlled trials as monotherapy and in combination with d4T or AZT/3TC . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-27, 1997;; Washington, DC. Abstract 370.
35 +
Markowitz M, Cao Y, Vesanen M, et al.  Recent HIV infection treated with AZT, 3TC, and a potent protease inhibitor . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-27, 1997;; Washington, DC. Abstract LB8.
36 +
Hammer SM, Squires KE, Fischl MA, Hughes MD, Grimes JM.  A placebo-controlled trial of indinavir in combination with two nucleoside analogs in HIV-infected persons with CD4+ cell counts <200/ mm3 . In: Programs and abstracts of the 8th Congress of Clinical Microbiology and Infectious Diseases ; May 25-28, 1997;; Lausanne, Switzerland. Abstract 90A.
37 +
Cameron B, Heath-Chiozzi M, Kravcik S, et al.  Prolongation of life and prevention of AIDS in advanced HIV immunodeficiency with ritonavir . In: Program and abstracts of the Third Conference on Retroviruses and Opportunistic Infections ; January 28-February 1, 1996;; Washington, DC. Abstract LB6a.
38 +
Lalezari J, Haubrich R, Burger HU, et al.  Improved survival and decreased progression of HIV in patients treated with saquinavir (Invirase, SQV) plus HIVID (zalcitabine, ddC) . In: Program and abstracts of the XI International Conference on AIDS ; July 7-12, 1996;; Vancouver, British Columbia. Abstract LB.B.6033.
39 +
Kelleher AD, Carr A, Zaunders J, Cooper DA.  Alterations in the immune response of human immunodeficiency virus (HIV)-infected subjects treated with an HIV-specific protease inhibitor, ritonavir . J Infect Dis . 1996;;173:321-329.
40 +
Connors M, Kovacs JA, Krevath S, et al.  HIV infection induces changes in CD4+ T cell phenotype and depletions within the CD4+ T cell repertoire that are not immediately restored by antiviral or immune-based therapies . Nat Med . 1997;;3:533-540.
41 +
Coffin JM.  Population dynamics in vivo: implications for genetic variation, pathogenesis and therapy . Science . 1995;;267:483-489.
42 +
Delta Coordinating Committee.  Delta: a randomized double-blind controlled trial comparing combinations of zidovudine plus didanosine or zalcitabine with zidovudine alone in HIV-infected individuals . Lancet . 1996;;348:283-291.
43 +
Saravolatz LD, Winslow DL, Collins G, et al.  Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with the acquired immunodeficiency syndrome or fewer than 200 CD4+ cells per cubic millimeter . N Engl J Med . 1996;;335:1099-1106.
44 +
Ho DD. Can  HIV be eradicated?  In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-27, 1997;; Washington, DC. Abstract S1.
45 +
Deeks SG, Smith M, Holodniy M, Kahn JO.  HIV-1 protease inhibitors: a review for clinicians . JAMA . 1997;;277:145-153.
46 +
Myers M, Montaner JSG, for the INCAS Study Group.  A randomized, double-blind, comparative trial of the effects of zidovudine, didanosine, and nevirapine combinations in antiviral naive, AIDS-free, HIV-infected patients with CD4+ cell counts 200-600μL . In: Program and abstracts of the XI International Conference on AIDS ; July 7-12, 1996;; Vancouver, British Columbia. Abstract Mo.B.294.
47 +
Conway B, Montaner JSG, Cooper D, et al.  Randomised, double-blind one-year study of the immunological and virological effects of nevirapine, didanosine and zidovudine combinations among antiretroviral-naive, AIDS-free patients with CD4+ cell counts of 200-600/μL . In: Program and abstracts of the Third International Congress on Drug Therapy in HIV Infection ; November 3-7, 1996;; Birmingham, England. Abstract OP7.1.
48 +
Wainberg MA, Birch C, for the  Boehringer-Ingelheim 1046 Study Team (INCAS trial). Phenotypic and genotypic resistance emergent in naive HIV-1 patients treated with combinations of reverse transcriptase inhibitors . In: Program and abstracts of the Third International Congress on Drug Therapy in HIV Infection ; November 3-7, 1996;; Birmingham, England. Abstract OP7.2.
49 +
Cohen C, Sun E, Cameron W, et al.  Ritonavirsaquinavir combination treatment in HIV-infected patients . In: Program and abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy ; September 15-18, 1996;; New Orleans, La. Abstract LB7b.
50 +
CAESAR Coordinating Committee.  Randomized trial of addition of lamivudine or lamivudine plus loviride to zidovudine-containing regimens for patients with HIV-1 infection: the CAESAR Trial . Lancet . 1997;;349:1413-1421.
51 +
Staszewski S, Bartlett J, Hill AM, Katlama C, Johnson J.  Reductions in HIV-1 disease progression for zidovudine/lamivudine relative to control treatments: a meta-analysis of controlled trials . AIDS . 1997;;11:474-483.
52 +
Katlama C, Valentin MA, Calvez S, et al.  ALTIS: a pilot open study of d4T/3TC antiretroviral naive and experienced patients . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-27, 1997;; Washington, DC. Abstract LB4.
53 +
Pollard R, Peterson D, Hardy D, et al.  Antiviral effect and safety of stavudine (d4T) and didanosine (ddI) combination therapy in HIV-infected subjects in an ongoing pilot randomized double-blind trial . In: Program and abstracts of the Third Conference on Retroviruses and Opportunistic Infections ; January28-February 1, 1996;; Washington, DC. Abstract 196.
54 +
Feinberg M.  Hidden dangers of incompletely suppressive antiretroviral therapy . Lancet . 1997;;349:1408-1409.
55 +
Centers for Disease Control and Prevention.  Update: provisional recommendations for chemoprophylaxis after occupational exposures to human immunodeficiency virus . MMWR Morb Mortal Wkly Rep . 1996;;45:468-472.
56 +
Panel on Clinical Practices for Treatment of HIV Infection, the US Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Federal Register. In press.
57 +
Connor EM, Sperling RS, Gelber R, et al, for the Pediatric AIDS Clinical Trials Group Protocol 076 Study Group.  Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment . N Engl J Med . 1994;;331:1173-1180.
58 +
Cooper ER, Nugent RP, Diaz C, et al.  After AIDS Clinical Trial 076: the changing pattern of zidovudine use during pregnancy, and the subsequent reduction in the vertical transmission of the human immunodeficiency virus in a cohort of infected women and their infants . J Infect Dis . 1996;;174:1207-1211.
59 +
Centers for Disease Control and Prevention.  AIDS among children—United States, 1996 . MMWR Morb Mortal Wkly Rep . 1996;;45:1006-1010.
60 +
Sperling RS, Shapiro DE, Coombs RW, et al, for the Pediatric AIDS Clinical Trials Group Protocol 076 Study Group.  Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant . N Engl J Med . 1996;;335:1621-1629.
61 +
Fiscus SA, Adimora AA, Schoenbach VJ, et al.  Perinatal HIV infection and the effect of zidovudine therapy on transmission in rural and urban counties . JAMA . 1996;;275:1483-1488.

Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Carpenter CCJ, Fischl MA,  Hammer SM, et al, for the International AIDS Society—USA. Antiretroviral therapy for HIV infection in 1996: recommendations of an international panel . JAMA . 1996;;276:146-154.
2 +
Pantaleo G, Graziosi C, Demarest JF, et al.  HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease . Nature . 1993;;362:355-358.
3 +
Embretson J, Zupancic M, Ribas JL, et al.  Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS . Nature . 1993;;362:359-362.
4 +
Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M.  Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection . Nature . 1995;;373:123-126.
5 +
Wei X, Ghosh SK, Taylor ME, et al.  Viral dynamics in human immunodeficiency virus type 1 . Nature . 1995;;373:117-122.
6 +
Perelson AS, Neuman AU, Markowitz M, Leonard JM, Ho DD.  HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span and viral generation time . Science . 1996;;271:1582-1586.
7 +
Cohen OJ, Pantaleo G, Holodniy M, et al.  Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissues . Proc Natl Acad Sci USA . 1995;;92:6017-6021.
8 +
Pantaleo G, Menzo S, Vaccarezza M, et al.  Studies in subjects with long-term nonprogressive human immunodeficiency virus infection . N Engl J Med . 1995;;332:209-216.
9 +
Haase AT, Henry K, Zupancic M, et al.  Quantitative image analysis of HIV-1 infection in lymphoid tissue . Science . 1996;;274:985-989.
10 +
Boswell SL, Mayer KH, Goldstein RS, Tucker L, Xu C, Anderson D.  The effect of HIV protease inhibitors on seminal proviral DNA . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-26, 1997;; Washington, DC. Abstract 202.
11 +
Pialoux G, Fournier S, Moulignier A, Poveda JD, Clavel F, Dupont B.  Central nervous system as sanctuary of HIV-1 in a patient treated with AZT + 3TC + indinavir . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-26, 1997;; Washington, DC. Abstract 233.
12 +
Gupta P, Mellors J, Kingsley L, et al.  High viral load in semen of HIV-1 infected men at all stages of disease and its reduction by antiretroviral therapy . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-26, 1997;; Washington, DC. Abstract 726.
13 +
Lennox J, Ellerbrock T, Palmore M, et al.  Effect of antiretroviral therapy on vaginal HIV RNA level . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-26, 1997;; Washington, DC. Abstract 727.
14 +
Mellors JW, Kinsley LA, Rinaldo CR, et al.  Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion . Ann Intern Med . 1995;;122:573-579.
15 +
Katzenstein DA, Hammer SM, Hughes MD, et al, for the AIDS Clinical Trials Group Study 175 Virology Study Team.  The relation of virologic and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells/μL . N Engl J Med . 1996;;335:1091-1098.
16 +
O'Brien TR, Blattner WA, Waters D, et al.  Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study . JAMA . 1996;;276:105-110.
17 +
Mellors JW, Kingsley L, Gupta P, et al.  Prognostic value of plasma HIV-1 RNA quantification in seropositive adult men . In: Program and abstracts of the XI International Conference on AIDS ; July 7-12, 1996;; Vancouver, British Columbia. Abstract We.B.410.
18 +
Hammer SM, Katzenstein DA, Hughes MD, et al, for the AIDS Clinical Trials Group Study 175 Study Team.  A trial comparing nucleoside monotherapy with combination therapy in HIV-infected adults with CD4 cell counts from 200 to 500/μL . N Engl J Med . 1996;;335:1081-1090.
19 +
Coombs RW, Welles SL, Hooper C, et al.  Association of plasma human immunodeficiency virus type-1 RNA level with risk of clinical progression in patients with advanced infection . J Infect Dis . 1996;;174:704-712.
20 +
Welles SL, Jackson JB, Yen-Lieberman B.  Prognostic value of plasma HIV-1 RNA levels in patients with advanced HIV-1 disease and with little or no zidovudine therapy . J Infect Dis . 1996;;174:696-703.
21 +
O'Brien WA, Hartigan PM, Martin D, et al.  Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of progression to AIDS: Veterans Affairs Cooperative Study Group on AIDS . N Engl J Med . 1996;;334:426-431.
22 +
Saag MS, Holodniy M, Kuritzkes DR, et al.  HIV viral load markers in clinical practice . Nat Med . 1996;; 2:625-629.
23 +
Brichacek B, Swindells S,Jannoff E, Pirrucello S, Stevenson M.  Increased plasma human immunodeficiency virus type 1 burden following antigenic challenge with vaccine . J Infect Dis . 1996;;174:1191-1199.
24 +
Staprans SL, Hamilton BL, Follansbee SE, et al.  Activation of virus replication after vaccination of HIV-1 infected individuals . J Exp Med . 1995;;182:1727-1737.
25 +
O'Brien WA, Grovit-Ferbas K, Namazi A, et al.  Human immunodeficiency virus-type 1 replication can be increased in peripheral blood of seropositive patients after influenza vaccination . Blood . 1995;;86:1082-1089.
26 +
De Gruttola V, Fleming T, Lin DY, Coombs R.  Perspective: validating surrogate markers—are we being naive? J Infect Dis . 1997;;175:237-245.
27 +
Mellors JW.  Prognosis in HIV-1 infection predicted by the quantity of virus in plasma . Science . 1996;;272:1167-1170.
28 +
Mellors JW, Munoz AM, Giorgi VJ, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med. In press.
29 +
Dean M, Carrington M, Winkler C, et al.  Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene . Science . 1996;;273:1856-1861.
30 +
Samson M, Libert F, Doranz BJ, et al.  Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene . Nature . 1996;;382:722-725.
31 +
Wong JK, Gunthard HF, Havlir DV, et al.  Reduction of HIV in blood and lymph nodes after potent antiretroviral therapy . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-26, 1997;; Washington, DC. Abstract LB10.
32 +
Gulick RM, Mellors JW, Havlir D, et al.  Potent and sustained antiretroviral activity of indinavir (IDV), zidovudine (ZDV), and lamivudine (3TC) . In: Program and abstracts of the XI International Conference on AIDS ; July 7-12, 1996;; Vancouver, British Columbia. Abstract Th.B.931.
33 +
Hirsch MS, Meibohm A, Rawlins S, Leavitt R, for the Protocol 039 (Indinavir) Study Group.  Indinavir (IDV) in combination with zidovudine (ZDV) and lamivudine (3TC) in ZDV-experienced patients with CD4+ cell counts ≤50 cells/mm3 . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-27, 1997;; Washington, DC. Abstract LB7.
34 +
Powderly WG, Sension M, Conant M, Stein A, Clendeninn N.  The efficacy of Viracept (nelfinavir mesylate, NFV) in pivotal phase I/II double-blind randomized controlled trials as monotherapy and in combination with d4T or AZT/3TC . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-27, 1997;; Washington, DC. Abstract 370.
35 +
Markowitz M, Cao Y, Vesanen M, et al.  Recent HIV infection treated with AZT, 3TC, and a potent protease inhibitor . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-27, 1997;; Washington, DC. Abstract LB8.
36 +
Hammer SM, Squires KE, Fischl MA, Hughes MD, Grimes JM.  A placebo-controlled trial of indinavir in combination with two nucleoside analogs in HIV-infected persons with CD4+ cell counts <200/ mm3 . In: Programs and abstracts of the 8th Congress of Clinical Microbiology and Infectious Diseases ; May 25-28, 1997;; Lausanne, Switzerland. Abstract 90A.
37 +
Cameron B, Heath-Chiozzi M, Kravcik S, et al.  Prolongation of life and prevention of AIDS in advanced HIV immunodeficiency with ritonavir . In: Program and abstracts of the Third Conference on Retroviruses and Opportunistic Infections ; January 28-February 1, 1996;; Washington, DC. Abstract LB6a.
38 +
Lalezari J, Haubrich R, Burger HU, et al.  Improved survival and decreased progression of HIV in patients treated with saquinavir (Invirase, SQV) plus HIVID (zalcitabine, ddC) . In: Program and abstracts of the XI International Conference on AIDS ; July 7-12, 1996;; Vancouver, British Columbia. Abstract LB.B.6033.
39 +
Kelleher AD, Carr A, Zaunders J, Cooper DA.  Alterations in the immune response of human immunodeficiency virus (HIV)-infected subjects treated with an HIV-specific protease inhibitor, ritonavir . J Infect Dis . 1996;;173:321-329.
40 +
Connors M, Kovacs JA, Krevath S, et al.  HIV infection induces changes in CD4+ T cell phenotype and depletions within the CD4+ T cell repertoire that are not immediately restored by antiviral or immune-based therapies . Nat Med . 1997;;3:533-540.
41 +
Coffin JM.  Population dynamics in vivo: implications for genetic variation, pathogenesis and therapy . Science . 1995;;267:483-489.
42 +
Delta Coordinating Committee.  Delta: a randomized double-blind controlled trial comparing combinations of zidovudine plus didanosine or zalcitabine with zidovudine alone in HIV-infected individuals . Lancet . 1996;;348:283-291.
43 +
Saravolatz LD, Winslow DL, Collins G, et al.  Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with the acquired immunodeficiency syndrome or fewer than 200 CD4+ cells per cubic millimeter . N Engl J Med . 1996;;335:1099-1106.
44 +
Ho DD. Can  HIV be eradicated?  In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-27, 1997;; Washington, DC. Abstract S1.
45 +
Deeks SG, Smith M, Holodniy M, Kahn JO.  HIV-1 protease inhibitors: a review for clinicians . JAMA . 1997;;277:145-153.
46 +
Myers M, Montaner JSG, for the INCAS Study Group.  A randomized, double-blind, comparative trial of the effects of zidovudine, didanosine, and nevirapine combinations in antiviral naive, AIDS-free, HIV-infected patients with CD4+ cell counts 200-600μL . In: Program and abstracts of the XI International Conference on AIDS ; July 7-12, 1996;; Vancouver, British Columbia. Abstract Mo.B.294.
47 +
Conway B, Montaner JSG, Cooper D, et al.  Randomised, double-blind one-year study of the immunological and virological effects of nevirapine, didanosine and zidovudine combinations among antiretroviral-naive, AIDS-free patients with CD4+ cell counts of 200-600/μL . In: Program and abstracts of the Third International Congress on Drug Therapy in HIV Infection ; November 3-7, 1996;; Birmingham, England. Abstract OP7.1.
48 +
Wainberg MA, Birch C, for the  Boehringer-Ingelheim 1046 Study Team (INCAS trial). Phenotypic and genotypic resistance emergent in naive HIV-1 patients treated with combinations of reverse transcriptase inhibitors . In: Program and abstracts of the Third International Congress on Drug Therapy in HIV Infection ; November 3-7, 1996;; Birmingham, England. Abstract OP7.2.
49 +
Cohen C, Sun E, Cameron W, et al.  Ritonavirsaquinavir combination treatment in HIV-infected patients . In: Program and abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy ; September 15-18, 1996;; New Orleans, La. Abstract LB7b.
50 +
CAESAR Coordinating Committee.  Randomized trial of addition of lamivudine or lamivudine plus loviride to zidovudine-containing regimens for patients with HIV-1 infection: the CAESAR Trial . Lancet . 1997;;349:1413-1421.
51 +
Staszewski S, Bartlett J, Hill AM, Katlama C, Johnson J.  Reductions in HIV-1 disease progression for zidovudine/lamivudine relative to control treatments: a meta-analysis of controlled trials . AIDS . 1997;;11:474-483.
52 +
Katlama C, Valentin MA, Calvez S, et al.  ALTIS: a pilot open study of d4T/3TC antiretroviral naive and experienced patients . In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections ; January 22-27, 1997;; Washington, DC. Abstract LB4.
53 +
Pollard R, Peterson D, Hardy D, et al.  Antiviral effect and safety of stavudine (d4T) and didanosine (ddI) combination therapy in HIV-infected subjects in an ongoing pilot randomized double-blind trial . In: Program and abstracts of the Third Conference on Retroviruses and Opportunistic Infections ; January28-February 1, 1996;; Washington, DC. Abstract 196.
54 +
Feinberg M.  Hidden dangers of incompletely suppressive antiretroviral therapy . Lancet . 1997;;349:1408-1409.
55 +
Centers for Disease Control and Prevention.  Update: provisional recommendations for chemoprophylaxis after occupational exposures to human immunodeficiency virus . MMWR Morb Mortal Wkly Rep . 1996;;45:468-472.
56 +
Panel on Clinical Practices for Treatment of HIV Infection, the US Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Federal Register. In press.
57 +
Connor EM, Sperling RS, Gelber R, et al, for the Pediatric AIDS Clinical Trials Group Protocol 076 Study Group.  Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment . N Engl J Med . 1994;;331:1173-1180.
58 +
Cooper ER, Nugent RP, Diaz C, et al.  After AIDS Clinical Trial 076: the changing pattern of zidovudine use during pregnancy, and the subsequent reduction in the vertical transmission of the human immunodeficiency virus in a cohort of infected women and their infants . J Infect Dis . 1996;;174:1207-1211.
59 +
Centers for Disease Control and Prevention.  AIDS among children—United States, 1996 . MMWR Morb Mortal Wkly Rep . 1996;;45:1006-1010.
60 +
Sperling RS, Shapiro DE, Coombs RW, et al, for the Pediatric AIDS Clinical Trials Group Protocol 076 Study Group.  Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant . N Engl J Med . 1996;;335:1621-1629.
61 +
Fiscus SA, Adimora AA, Schoenbach VJ, et al.  Perinatal HIV infection and the effect of zidovudine therapy on transmission in rural and urban counties . JAMA . 1996;;275:1483-1488.

Letters

Submit a Letter
CME Course for:


You need to register in order to view this quiz.


To understand the clinical management of acute heart failure syndromes.
Accreditation Information The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
To view and print your certificate and access a summary of your CME courses go to My CME.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
Cone
AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
Submit a Response

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

© 2012 American Medical Association. All Rights Reserved.
Powered bySilverchair Information Systems