Efficacy and Safety of Adefovir Dipivoxil With Antiretroviral Therapy: A Randomized Controlled Trial
CONTEXT Adefovir dipivoxil is a nucleotide analog that has demonstrated effective antiretroviral activity against human immunodeficiency virus (HIV) with once-daily administration. OBJECTIVE To determine if adefovir confers antiretroviral or immunologic benefit when added to stable antiretroviral th...
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| Veröffentlicht in: | JAMA : the journal of the American Medical Association 1999-12, Vol.282 (24), p.2305-2312 |
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| creator | Kahn, James Lagakos, Stephen Wulfsohn, Michael Cherng, Deborah Miller, Michael Cherrington, Julie Hardy, David Beall, Gildon Cooper, Richard Murphy, Robert Basgoz, Nesli Ng, Edmund Deeks, Steven Winslow, Dean Toole, John J Coakley, Dion for the GS-408 Study Team |
| description | CONTEXT Adefovir dipivoxil is a nucleotide analog that has demonstrated effective
antiretroviral activity against human immunodeficiency virus (HIV) with once-daily
administration. OBJECTIVE To determine if adefovir confers antiretroviral or immunologic benefit
when added to stable antiretroviral therapy. DESIGN Multicenter, 24-week, randomized, double-blind, placebo-controlled study.
Enrollment was conducted from June 3, 1996, through May 6, 1997. SETTING Thirty-three US HIV treatment centers. PARTICIPANTS Of 1171 patients screened, 442 patients infected with HIV receiving
stable antiretroviral therapy for at least 8 weeks with plasma HIV RNA greater
than 2500 copies/mL and CD4+ cell count above 0.20 × 109/L were randomized. INTERVENTION Patients were randomized to receive either a single 120-mg/d dose of
adefovir dipivoxil (n = 219) or an indistinguishable placebo (n = 223). All
patients received L-carnitine, 500 mg/d. Open-label adefovir was offered after
24 weeks and was continued until the end of the study. MAIN OUTCOME MEASURES Changes in HIV RNA from baseline, based on area under the curve and
CD4+ cell levels, adverse events, and effect of baseline genotypic
resistance on response to adefovir. RESULTS Patients assigned to adefovir demonstrated a 0.4-log10 decline
from baseline in HIV RNA compared with no change in the placebo group (P |
| doi_str_mv | 10.1001/jama.282.24.2305 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_17591592</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><ama_id>192232</ama_id><sourcerecordid>17591592</sourcerecordid><originalsourceid>FETCH-LOGICAL-a354t-ab09ec143229ea8a0900aa8f8f15813756f8219872ae93ec153ec232b94b9db73</originalsourceid><addsrcrecordid>eNpd0c1LwzAYBvAgis6Pu14kiHjrzJs0a-JtzE8YCDrxWN62CWak7Uw7cf71ZjgRzCEJvD8eHhJCjoENgTG4nGONQ674kKdDLpjcIgOQQiVCarVNBoxplWSpSvfIftfNWVwgsl2yB2wEXEA2INWNta7EckWxqegzWtOvaGvpuDK2_XCBXruF-2g_naevrn-j46Z3wfRhPUNPZ28m4GJ1Rcf0KQa0tfsyFZ20TRTex-ssOPSHZMei78zR5jwgL7c3s8l9Mn28e5iMpwkKmfYJFkybElLBuTaokGnGEJVVFqSKxeXIKg5aZRyNFlHKuHHBC50WuioycUAufnIXoX1fmq7Pa9eVxntsTLvscsikBql5hGf_4LxdhiZ2yzmAYGoE67TTDVoWtanyRXA1hlX--3gRnG8AdiV6G7ApXffnOAgYQWQnPyx-1t9Q89hcfAMfmYVg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>211308617</pqid></control><display><type>article</type><title>Efficacy and Safety of Adefovir Dipivoxil With Antiretroviral Therapy: A Randomized Controlled Trial</title><source>MEDLINE</source><source>American Medical Association Journals</source><creator>Kahn, James ; Lagakos, Stephen ; Wulfsohn, Michael ; Cherng, Deborah ; Miller, Michael ; Cherrington, Julie ; Hardy, David ; Beall, Gildon ; Cooper, Richard ; Murphy, Robert ; Basgoz, Nesli ; Ng, Edmund ; Deeks, Steven ; Winslow, Dean ; Toole, John J ; Coakley, Dion ; for the GS-408 Study Team</creator><creatorcontrib>Kahn, James ; Lagakos, Stephen ; Wulfsohn, Michael ; Cherng, Deborah ; Miller, Michael ; Cherrington, Julie ; Hardy, David ; Beall, Gildon ; Cooper, Richard ; Murphy, Robert ; Basgoz, Nesli ; Ng, Edmund ; Deeks, Steven ; Winslow, Dean ; Toole, John J ; Coakley, Dion ; for the GS-408 Study Team</creatorcontrib><description>CONTEXT Adefovir dipivoxil is a nucleotide analog that has demonstrated effective
antiretroviral activity against human immunodeficiency virus (HIV) with once-daily
administration. OBJECTIVE To determine if adefovir confers antiretroviral or immunologic benefit
when added to stable antiretroviral therapy. DESIGN Multicenter, 24-week, randomized, double-blind, placebo-controlled study.
Enrollment was conducted from June 3, 1996, through May 6, 1997. SETTING Thirty-three US HIV treatment centers. PARTICIPANTS Of 1171 patients screened, 442 patients infected with HIV receiving
stable antiretroviral therapy for at least 8 weeks with plasma HIV RNA greater
than 2500 copies/mL and CD4+ cell count above 0.20 × 109/L were randomized. INTERVENTION Patients were randomized to receive either a single 120-mg/d dose of
adefovir dipivoxil (n = 219) or an indistinguishable placebo (n = 223). All
patients received L-carnitine, 500 mg/d. Open-label adefovir was offered after
24 weeks and was continued until the end of the study. MAIN OUTCOME MEASURES Changes in HIV RNA from baseline, based on area under the curve and
CD4+ cell levels, adverse events, and effect of baseline genotypic
resistance on response to adefovir. RESULTS Patients assigned to adefovir demonstrated a 0.4-log10 decline
from baseline in HIV RNA compared with no change in the placebo group (P<.001), which continued through 48 weeks. CD4+ cell counts did not change. During the initial 24 weeks, elevated
hepatic enzyme levels (P<.001), gastrointestinal
tract complaints (P<.001), and weight loss (P<.001) were associated with use of adefovir. Between
24 weeks and 48 weeks elevations in serum creatinine occurred in 60% of patients,
usually returning to baseline after discontinuation of adefovir. Patients
with lamivudine or lamivudine and zidovudine resistance mutations demonstrated
anti–HIV effects with adefovir (P≤.01 vs
placebo group). CONCLUSIONS This study suggests that once-daily adefovir therapy reduces HIV RNA
and is active against isolates resistant to lamivudine or lamivudine and zidovudine.
Nephrotoxicity occurred when treatment extended beyond 24 weeks but was reversible.</description><identifier>ISSN: 0098-7484</identifier><identifier>EISSN: 1538-3598</identifier><identifier>DOI: 10.1001/jama.282.24.2305</identifier><identifier>PMID: 10612317</identifier><identifier>CODEN: JAMAAP</identifier><language>eng</language><publisher>Chicago, IL: American Medical Association</publisher><subject>adefovir dipivoxil ; Adenine - analogs & derivatives ; Adenine - therapeutic use ; Adult ; Anti-HIV Agents - pharmacology ; Anti-HIV Agents - therapeutic use ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Biological and medical sciences ; Carnitine ; CD4 Lymphocyte Count ; Clinical trials ; Double-Blind Method ; drug resistance ; Drug Resistance, Microbial ; Drug therapy ; Drug Therapy, Combination ; Female ; Genotype ; HIV ; HIV Infections - drug therapy ; HIV Infections - immunology ; HIV Infections - virology ; HIV-1 - drug effects ; HIV-1 - genetics ; Human immunodeficiency virus ; Human viral diseases ; Humans ; Infectious diseases ; lamivudine ; Lamivudine - pharmacology ; Male ; Medical research ; Medical sciences ; nephrotoxicity ; nucleotides ; Organophosphonates ; Pharmacology. Drug treatments ; Retrovirus ; Reverse Transcriptase Inhibitors - therapeutic use ; Ribonucleic acid ; RNA ; RNA, Viral ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids ; Viral Load ; zidovudine ; Zidovudine - pharmacology</subject><ispartof>JAMA : the journal of the American Medical Association, 1999-12, Vol.282 (24), p.2305-2312</ispartof><rights>2000 INIST-CNRS</rights><rights>Copyright American Medical Association Dec 22/29, 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jamanetwork.com/journals/jama/articlepdf/10.1001/jama.282.24.2305$$EPDF$$P50$$Gama$$H</linktopdf><linktohtml>$$Uhttps://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.282.24.2305$$EHTML$$P50$$Gama$$H</linktohtml><link.rule.ids>64,314,776,780,3327,27901,27902,76231,76234</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1213161$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10612317$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kahn, James</creatorcontrib><creatorcontrib>Lagakos, Stephen</creatorcontrib><creatorcontrib>Wulfsohn, Michael</creatorcontrib><creatorcontrib>Cherng, Deborah</creatorcontrib><creatorcontrib>Miller, Michael</creatorcontrib><creatorcontrib>Cherrington, Julie</creatorcontrib><creatorcontrib>Hardy, David</creatorcontrib><creatorcontrib>Beall, Gildon</creatorcontrib><creatorcontrib>Cooper, Richard</creatorcontrib><creatorcontrib>Murphy, Robert</creatorcontrib><creatorcontrib>Basgoz, Nesli</creatorcontrib><creatorcontrib>Ng, Edmund</creatorcontrib><creatorcontrib>Deeks, Steven</creatorcontrib><creatorcontrib>Winslow, Dean</creatorcontrib><creatorcontrib>Toole, John J</creatorcontrib><creatorcontrib>Coakley, Dion</creatorcontrib><creatorcontrib>for the GS-408 Study Team</creatorcontrib><title>Efficacy and Safety of Adefovir Dipivoxil With Antiretroviral Therapy: A Randomized Controlled Trial</title><title>JAMA : the journal of the American Medical Association</title><addtitle>JAMA</addtitle><description>CONTEXT Adefovir dipivoxil is a nucleotide analog that has demonstrated effective
antiretroviral activity against human immunodeficiency virus (HIV) with once-daily
administration. OBJECTIVE To determine if adefovir confers antiretroviral or immunologic benefit
when added to stable antiretroviral therapy. DESIGN Multicenter, 24-week, randomized, double-blind, placebo-controlled study.
Enrollment was conducted from June 3, 1996, through May 6, 1997. SETTING Thirty-three US HIV treatment centers. PARTICIPANTS Of 1171 patients screened, 442 patients infected with HIV receiving
stable antiretroviral therapy for at least 8 weeks with plasma HIV RNA greater
than 2500 copies/mL and CD4+ cell count above 0.20 × 109/L were randomized. INTERVENTION Patients were randomized to receive either a single 120-mg/d dose of
adefovir dipivoxil (n = 219) or an indistinguishable placebo (n = 223). All
patients received L-carnitine, 500 mg/d. Open-label adefovir was offered after
24 weeks and was continued until the end of the study. MAIN OUTCOME MEASURES Changes in HIV RNA from baseline, based on area under the curve and
CD4+ cell levels, adverse events, and effect of baseline genotypic
resistance on response to adefovir. RESULTS Patients assigned to adefovir demonstrated a 0.4-log10 decline
from baseline in HIV RNA compared with no change in the placebo group (P<.001), which continued through 48 weeks. CD4+ cell counts did not change. During the initial 24 weeks, elevated
hepatic enzyme levels (P<.001), gastrointestinal
tract complaints (P<.001), and weight loss (P<.001) were associated with use of adefovir. Between
24 weeks and 48 weeks elevations in serum creatinine occurred in 60% of patients,
usually returning to baseline after discontinuation of adefovir. Patients
with lamivudine or lamivudine and zidovudine resistance mutations demonstrated
anti–HIV effects with adefovir (P≤.01 vs
placebo group). CONCLUSIONS This study suggests that once-daily adefovir therapy reduces HIV RNA
and is active against isolates resistant to lamivudine or lamivudine and zidovudine.
Nephrotoxicity occurred when treatment extended beyond 24 weeks but was reversible.</description><subject>adefovir dipivoxil</subject><subject>Adenine - analogs & derivatives</subject><subject>Adenine - therapeutic use</subject><subject>Adult</subject><subject>Anti-HIV Agents - pharmacology</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>Carnitine</subject><subject>CD4 Lymphocyte Count</subject><subject>Clinical trials</subject><subject>Double-Blind Method</subject><subject>drug resistance</subject><subject>Drug Resistance, Microbial</subject><subject>Drug therapy</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>Genotype</subject><subject>HIV</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - virology</subject><subject>HIV-1 - drug effects</subject><subject>HIV-1 - genetics</subject><subject>Human immunodeficiency virus</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>lamivudine</subject><subject>Lamivudine - pharmacology</subject><subject>Male</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>nephrotoxicity</subject><subject>nucleotides</subject><subject>Organophosphonates</subject><subject>Pharmacology. Drug treatments</subject><subject>Retrovirus</subject><subject>Reverse Transcriptase Inhibitors - therapeutic use</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Viral</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><subject>Viral Load</subject><subject>zidovudine</subject><subject>Zidovudine - pharmacology</subject><issn>0098-7484</issn><issn>1538-3598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0c1LwzAYBvAgis6Pu14kiHjrzJs0a-JtzE8YCDrxWN62CWak7Uw7cf71ZjgRzCEJvD8eHhJCjoENgTG4nGONQ674kKdDLpjcIgOQQiVCarVNBoxplWSpSvfIftfNWVwgsl2yB2wEXEA2INWNta7EckWxqegzWtOvaGvpuDK2_XCBXruF-2g_naevrn-j46Z3wfRhPUNPZ28m4GJ1Rcf0KQa0tfsyFZ20TRTex-ssOPSHZMei78zR5jwgL7c3s8l9Mn28e5iMpwkKmfYJFkybElLBuTaokGnGEJVVFqSKxeXIKg5aZRyNFlHKuHHBC50WuioycUAufnIXoX1fmq7Pa9eVxntsTLvscsikBql5hGf_4LxdhiZ2yzmAYGoE67TTDVoWtanyRXA1hlX--3gRnG8AdiV6G7ApXffnOAgYQWQnPyx-1t9Q89hcfAMfmYVg</recordid><startdate>19991222</startdate><enddate>19991222</enddate><creator>Kahn, James</creator><creator>Lagakos, Stephen</creator><creator>Wulfsohn, Michael</creator><creator>Cherng, Deborah</creator><creator>Miller, Michael</creator><creator>Cherrington, Julie</creator><creator>Hardy, David</creator><creator>Beall, Gildon</creator><creator>Cooper, Richard</creator><creator>Murphy, Robert</creator><creator>Basgoz, Nesli</creator><creator>Ng, Edmund</creator><creator>Deeks, Steven</creator><creator>Winslow, Dean</creator><creator>Toole, John J</creator><creator>Coakley, Dion</creator><creator>for the GS-408 Study Team</creator><general>American Medical Association</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QL</scope><scope>7QP</scope><scope>7TK</scope><scope>7TS</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7T2</scope><scope>7U2</scope></search><sort><creationdate>19991222</creationdate><title>Efficacy and Safety of Adefovir Dipivoxil With Antiretroviral Therapy: A Randomized Controlled Trial</title><author>Kahn, James ; Lagakos, Stephen ; Wulfsohn, Michael ; Cherng, Deborah ; Miller, Michael ; Cherrington, Julie ; Hardy, David ; Beall, Gildon ; Cooper, Richard ; Murphy, Robert ; Basgoz, Nesli ; Ng, Edmund ; Deeks, Steven ; Winslow, Dean ; Toole, John J ; Coakley, Dion ; for the GS-408 Study Team</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a354t-ab09ec143229ea8a0900aa8f8f15813756f8219872ae93ec153ec232b94b9db73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>adefovir dipivoxil</topic><topic>Adenine - analogs & derivatives</topic><topic>Adenine - therapeutic use</topic><topic>Adult</topic><topic>Anti-HIV Agents - pharmacology</topic><topic>Anti-HIV Agents - therapeutic use</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Biological and medical sciences</topic><topic>Carnitine</topic><topic>CD4 Lymphocyte Count</topic><topic>Clinical trials</topic><topic>Double-Blind Method</topic><topic>drug resistance</topic><topic>Drug Resistance, Microbial</topic><topic>Drug therapy</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>Genotype</topic><topic>HIV</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - immunology</topic><topic>HIV Infections - virology</topic><topic>HIV-1 - drug effects</topic><topic>HIV-1 - genetics</topic><topic>Human immunodeficiency virus</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>lamivudine</topic><topic>Lamivudine - pharmacology</topic><topic>Male</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>nephrotoxicity</topic><topic>nucleotides</topic><topic>Organophosphonates</topic><topic>Pharmacology. Drug treatments</topic><topic>Retrovirus</topic><topic>Reverse Transcriptase Inhibitors - therapeutic use</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Viral</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><topic>Viral Load</topic><topic>zidovudine</topic><topic>Zidovudine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kahn, James</creatorcontrib><creatorcontrib>Lagakos, Stephen</creatorcontrib><creatorcontrib>Wulfsohn, Michael</creatorcontrib><creatorcontrib>Cherng, Deborah</creatorcontrib><creatorcontrib>Miller, Michael</creatorcontrib><creatorcontrib>Cherrington, Julie</creatorcontrib><creatorcontrib>Hardy, David</creatorcontrib><creatorcontrib>Beall, Gildon</creatorcontrib><creatorcontrib>Cooper, Richard</creatorcontrib><creatorcontrib>Murphy, Robert</creatorcontrib><creatorcontrib>Basgoz, Nesli</creatorcontrib><creatorcontrib>Ng, Edmund</creatorcontrib><creatorcontrib>Deeks, Steven</creatorcontrib><creatorcontrib>Winslow, Dean</creatorcontrib><creatorcontrib>Toole, John J</creatorcontrib><creatorcontrib>Coakley, Dion</creatorcontrib><creatorcontrib>for the GS-408 Study Team</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Safety Science and Risk</collection><jtitle>JAMA : the journal of the American Medical Association</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kahn, James</au><au>Lagakos, Stephen</au><au>Wulfsohn, Michael</au><au>Cherng, Deborah</au><au>Miller, Michael</au><au>Cherrington, Julie</au><au>Hardy, David</au><au>Beall, Gildon</au><au>Cooper, Richard</au><au>Murphy, Robert</au><au>Basgoz, Nesli</au><au>Ng, Edmund</au><au>Deeks, Steven</au><au>Winslow, Dean</au><au>Toole, John J</au><au>Coakley, Dion</au><au>for the GS-408 Study Team</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and Safety of Adefovir Dipivoxil With Antiretroviral Therapy: A Randomized Controlled Trial</atitle><jtitle>JAMA : the journal of the American Medical Association</jtitle><addtitle>JAMA</addtitle><date>1999-12-22</date><risdate>1999</risdate><volume>282</volume><issue>24</issue><spage>2305</spage><epage>2312</epage><pages>2305-2312</pages><issn>0098-7484</issn><eissn>1538-3598</eissn><coden>JAMAAP</coden><abstract>CONTEXT Adefovir dipivoxil is a nucleotide analog that has demonstrated effective
antiretroviral activity against human immunodeficiency virus (HIV) with once-daily
administration. OBJECTIVE To determine if adefovir confers antiretroviral or immunologic benefit
when added to stable antiretroviral therapy. DESIGN Multicenter, 24-week, randomized, double-blind, placebo-controlled study.
Enrollment was conducted from June 3, 1996, through May 6, 1997. SETTING Thirty-three US HIV treatment centers. PARTICIPANTS Of 1171 patients screened, 442 patients infected with HIV receiving
stable antiretroviral therapy for at least 8 weeks with plasma HIV RNA greater
than 2500 copies/mL and CD4+ cell count above 0.20 × 109/L were randomized. INTERVENTION Patients were randomized to receive either a single 120-mg/d dose of
adefovir dipivoxil (n = 219) or an indistinguishable placebo (n = 223). All
patients received L-carnitine, 500 mg/d. Open-label adefovir was offered after
24 weeks and was continued until the end of the study. MAIN OUTCOME MEASURES Changes in HIV RNA from baseline, based on area under the curve and
CD4+ cell levels, adverse events, and effect of baseline genotypic
resistance on response to adefovir. RESULTS Patients assigned to adefovir demonstrated a 0.4-log10 decline
from baseline in HIV RNA compared with no change in the placebo group (P<.001), which continued through 48 weeks. CD4+ cell counts did not change. During the initial 24 weeks, elevated
hepatic enzyme levels (P<.001), gastrointestinal
tract complaints (P<.001), and weight loss (P<.001) were associated with use of adefovir. Between
24 weeks and 48 weeks elevations in serum creatinine occurred in 60% of patients,
usually returning to baseline after discontinuation of adefovir. Patients
with lamivudine or lamivudine and zidovudine resistance mutations demonstrated
anti–HIV effects with adefovir (P≤.01 vs
placebo group). CONCLUSIONS This study suggests that once-daily adefovir therapy reduces HIV RNA
and is active against isolates resistant to lamivudine or lamivudine and zidovudine.
Nephrotoxicity occurred when treatment extended beyond 24 weeks but was reversible.</abstract><cop>Chicago, IL</cop><pub>American Medical Association</pub><pmid>10612317</pmid><doi>10.1001/jama.282.24.2305</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0098-7484 |
| ispartof | JAMA : the journal of the American Medical Association, 1999-12, Vol.282 (24), p.2305-2312 |
| issn | 0098-7484 1538-3598 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_17591592 |
| source | MEDLINE; American Medical Association Journals |
| subjects | adefovir dipivoxil Adenine - analogs & derivatives Adenine - therapeutic use Adult Anti-HIV Agents - pharmacology Anti-HIV Agents - therapeutic use Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences Carnitine CD4 Lymphocyte Count Clinical trials Double-Blind Method drug resistance Drug Resistance, Microbial Drug therapy Drug Therapy, Combination Female Genotype HIV HIV Infections - drug therapy HIV Infections - immunology HIV Infections - virology HIV-1 - drug effects HIV-1 - genetics Human immunodeficiency virus Human viral diseases Humans Infectious diseases lamivudine Lamivudine - pharmacology Male Medical research Medical sciences nephrotoxicity nucleotides Organophosphonates Pharmacology. Drug treatments Retrovirus Reverse Transcriptase Inhibitors - therapeutic use Ribonucleic acid RNA RNA, Viral Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral Load zidovudine Zidovudine - pharmacology |
| title | Efficacy and Safety of Adefovir Dipivoxil With Antiretroviral Therapy: A Randomized Controlled Trial |
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