schliessen

Filtern

 

Bibliotheken

Effect of daily aciclovir on HIV disease progression in individuals in Rakai, Uganda, co-infected with HIV-1 and herpes simplex virus type 2: a randomised, double-blind placebo-controlled trial

Summary Background Daily suppression of herpes simplex virus type 2 (HSV-2) reduces plasma HIV-1 concentrations and modestly delayed HIV-1 disease progression in one clinical trial. We investigated the effect of daily suppressive aciclovir on HIV-1 disease progression in Rakai, Uganda. Methods We di... Full description

Journal Title: The Lancet infectious diseases 2012, Vol.12 (6), p.441-448
Main Author: Reynolds, Steven J, MD
Other Authors: Makumbi, Fred, PhD , Newell, Kevin, MPH , Kiwanuka, Noah, MBChB , Ssebbowa, Paschal, MBChB , Mondo, George, BSc , Boaz, Iga, BSc , Wawer, Maria J, Prof , Gray, Ronald H, Prof , Serwadda, David, Prof , Quinn, Thomas C, Prof
Format: Electronic Article Electronic Article
Language: English
Subjects:
Age
Sex
Quelle: Alma/SFX Local Collection
Publisher: London: Elsevier Ltd
ID: ISSN: 1473-3099
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: cdi_proquest_miscellaneous_1017621387
title: Effect of daily aciclovir on HIV disease progression in individuals in Rakai, Uganda, co-infected with HIV-1 and herpes simplex virus type 2: a randomised, double-blind placebo-controlled trial
format: Article
creator:
  • Reynolds, Steven J, MD
  • Makumbi, Fred, PhD
  • Newell, Kevin, MPH
  • Kiwanuka, Noah, MBChB
  • Ssebbowa, Paschal, MBChB
  • Mondo, George, BSc
  • Boaz, Iga, BSc
  • Wawer, Maria J, Prof
  • Gray, Ronald H, Prof
  • Serwadda, David, Prof
  • Quinn, Thomas C, Prof
subjects:
  • Acyclovir - administration & dosage
  • Acyclovir - therapeutic use
  • Adult
  • Age
  • Antibiotics. Antiinfectious agents. Antiparasitic agents
  • antiretroviral therapy
  • Antiviral agents
  • Antiviral Agents - administration & dosage
  • Antiviral Agents - therapeutic use
  • Biological and medical sciences
  • CD4 antigen
  • CD4 Lymphocyte Count
  • Clinical trials
  • Coinfection
  • Data processing
  • Disease Progression
  • Double-Blind Method
  • Female
  • Herpes
  • Herpes simplex
  • Herpes Simplex - complications
  • Herpes Simplex - drug therapy
  • Herpes Simplex - virology
  • Herpes simplex virus
  • Herpes simplex virus 2
  • Herpesvirus 2, Human
  • Herpesvirus diseases
  • HIV (Viruses)
  • HIV Infections - complications
  • HIV Infections - drug therapy
  • HIV Infections - immunology
  • HIV Infections - virology
  • HIV-1
  • Human immunodeficiency virus 1
  • Human viral diseases
  • Humans
  • Hypersensitivity
  • Immunodeficiencies
  • Immunodeficiencies. Immunoglobulinopathies
  • Immunopathology
  • Infectious Disease
  • Infectious diseases
  • Intention to Treat Analysis
  • Kaplan-Meier Estimate
  • Male
  • Medical colleges
  • Medical sciences
  • Middle Aged
  • Pharmacology. Drug treatments
  • Proportional Hazards Models
  • Risk assessment
  • Sex
  • Uganda
  • Ulcers
  • Viral diseases
  • Viral diseases of the lymphoid tissue and the blood. Aids
  • Viral Load
  • Virus diseases
  • Young Adult
ispartof: The Lancet infectious diseases, 2012, Vol.12 (6), p.441-448
description: Summary Background Daily suppression of herpes simplex virus type 2 (HSV-2) reduces plasma HIV-1 concentrations and modestly delayed HIV-1 disease progression in one clinical trial. We investigated the effect of daily suppressive aciclovir on HIV-1 disease progression in Rakai, Uganda. Methods We did a single site, parallel, randomised, controlled trial of HIV-1, HSV-2 dually infected adults with CD4 cell counts of 300–400 cells per μL. We excluded individuals who had an AIDS-defining illness or active genital ulcer disease, and those that were taking antiretroviral therapy. Participants were randomly assigned (1:1) with computer-generated random numbers in blocks of four to receive either aciclovir 400 mg orally twice daily or placebo; participants were followed up for 24 months. All study staff and participants were masked to treatment, except for the two statisticians. The primary outcome was CD4 cell count less than 250 cells per μL or initiation of antiretroviral therapy for WHO stage 4 disease. Our intention-to-treat analysis used Cox proportional hazards models, adjusting for baseline log10 viral load, CD4 cell count, sex, and age to assess the risk of disease progression. We also investigated the effect of suppressive HSV-2 treatment stratified by baseline HIV viral load with a Cox proportional hazards model. This trial is registered with ClinicalTrials.gov , number NCT00405821. Findings 440 participants were randomly assigned, 220 to each group. 110 participants in the placebo group and 95 participants in the treatment group reached the primary endpoint (adjusted hazard ratio [HR] 0·75, 95% CI 0·58–0·99; p=0·040). 24 participants in the placebo group and 22 in the treatment group were censored, but all contributed data for the final analysis. In a subanalysis stratified by baseline HIV viral load, participants with a baseline viral load of 50 000 copies mL or more in the treatment group had a reduced HIV disease progression compared with those in the placebo group (0·62, 0·43–0·96; p=0·03). No significant difference in HIV disease progression existed between participants in the treatment group and those in the placebo group who had baseline HIV viral loads of less than 50 000 copies per mL (0·90, 0·54–1·5; p=0·688). No safety issues related to aciclovir treatment were identified. Interpretation Aciclovir reduces the rate of disease progression, with the greatest effect in individuals with a high baseline viral load. Suppressive aciclovir might be
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 1473-3099
fulltext: fulltext
issn:
  • 1473-3099
  • 1474-4457
url: Link


@attributes
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
RANK2.4684083
LOCALfalse
PrimoNMBib
record
control
sourceidgale_proqu
recordidTN_cdi_proquest_miscellaneous_1017621387
sourceformatXML
sourcesystemPC
galeidA290968394
sourcerecordidA290968394
originalsourceidFETCH-LOGICAL-1634t-485ddcdccf43ca97a00c49b1451837fa871402e416c6da69d7926e69bb690e813
addsrcrecordideNqNkmFr1TAUhosobk5_ghIQYcLtTJq0aRSUMaYbDAR1fi1pcnqXLbe5Ju3V-_P8Z57eO53uy6SFtulz3vMm582yp4weMMqqV5-ZkDznVKl9VryUlHKZ83vZLi6LXIhS3t-8b5Gd7FFKl5Qyyah4mO0UheC8kGo3-3ncdWAGEjpitfNroo0zPqxcJKEnJ6dfiXUJdAKyjGEeISWH6266rVs5O2qfps9P-kq7GTmf697qGTEhd_0kDJZ8d8PFpJQzgj_JBcQlJJLcYunhB8FOYyLDegmkeE00iciEBfa0M2LD2HrIW4_NyNJrA23ITeiHGLxH5SE67R9nDzo0AU-un3vZ-fvjL0cn-dnHD6dHh2c5q7gYclGX1hprTCe40UpqSo1QLRMlq7nsdC2ZoAUIVpnK6kpZqYoKKtW2laJQM76X7W918SC-jZCGBl0a8F73EMbUMMrrUpWV5P-BMlkVjNcS0ee30Mswxh43MlGKckZVidTBlpprDw2ebBiiNnhZWDg8EOgcrh8Wiqqq5kpgweyvgnZMrp9G1yc3vxjSXI8p_YuXW9zEkFKErllGt9BxjSYmH1WziVszZalhRbOJWzNt9Nm1-7FdgP1T9TtfCLy4BnQy2nc4XePSDVcqXspyMvDmlgHjBj24adYYyzttvNtWA85_5SA2yTjoDVgXMYONDe5Ohbe3FAyGzqHlK1hDuplJk4qGbkUmDVZsFDj_BXTdGDw
sourcetypeAggregation Database
isCDItrue
recordtypearticle
pqid1019031095
display
typearticle
titleEffect of daily aciclovir on HIV disease progression in individuals in Rakai, Uganda, co-infected with HIV-1 and herpes simplex virus type 2: a randomised, double-blind placebo-controlled trial
sourceAlma/SFX Local Collection
creatorReynolds, Steven J, MD ; Makumbi, Fred, PhD ; Newell, Kevin, MPH ; Kiwanuka, Noah, MBChB ; Ssebbowa, Paschal, MBChB ; Mondo, George, BSc ; Boaz, Iga, BSc ; Wawer, Maria J, Prof ; Gray, Ronald H, Prof ; Serwadda, David, Prof ; Quinn, Thomas C, Prof
creatorcontribReynolds, Steven J, MD ; Makumbi, Fred, PhD ; Newell, Kevin, MPH ; Kiwanuka, Noah, MBChB ; Ssebbowa, Paschal, MBChB ; Mondo, George, BSc ; Boaz, Iga, BSc ; Wawer, Maria J, Prof ; Gray, Ronald H, Prof ; Serwadda, David, Prof ; Quinn, Thomas C, Prof
descriptionSummary Background Daily suppression of herpes simplex virus type 2 (HSV-2) reduces plasma HIV-1 concentrations and modestly delayed HIV-1 disease progression in one clinical trial. We investigated the effect of daily suppressive aciclovir on HIV-1 disease progression in Rakai, Uganda. Methods We did a single site, parallel, randomised, controlled trial of HIV-1, HSV-2 dually infected adults with CD4 cell counts of 300–400 cells per μL. We excluded individuals who had an AIDS-defining illness or active genital ulcer disease, and those that were taking antiretroviral therapy. Participants were randomly assigned (1:1) with computer-generated random numbers in blocks of four to receive either aciclovir 400 mg orally twice daily or placebo; participants were followed up for 24 months. All study staff and participants were masked to treatment, except for the two statisticians. The primary outcome was CD4 cell count less than 250 cells per μL or initiation of antiretroviral therapy for WHO stage 4 disease. Our intention-to-treat analysis used Cox proportional hazards models, adjusting for baseline log10 viral load, CD4 cell count, sex, and age to assess the risk of disease progression. We also investigated the effect of suppressive HSV-2 treatment stratified by baseline HIV viral load with a Cox proportional hazards model. This trial is registered with ClinicalTrials.gov , number NCT00405821. Findings 440 participants were randomly assigned, 220 to each group. 110 participants in the placebo group and 95 participants in the treatment group reached the primary endpoint (adjusted hazard ratio [HR] 0·75, 95% CI 0·58–0·99; p=0·040). 24 participants in the placebo group and 22 in the treatment group were censored, but all contributed data for the final analysis. In a subanalysis stratified by baseline HIV viral load, participants with a baseline viral load of 50 000 copies mL or more in the treatment group had a reduced HIV disease progression compared with those in the placebo group (0·62, 0·43–0·96; p=0·03). No significant difference in HIV disease progression existed between participants in the treatment group and those in the placebo group who had baseline HIV viral loads of less than 50 000 copies per mL (0·90, 0·54–1·5; p=0·688). No safety issues related to aciclovir treatment were identified. Interpretation Aciclovir reduces the rate of disease progression, with the greatest effect in individuals with a high baseline viral load. Suppressive aciclovir might be warranted for individuals dually infected with HSV-2 and HIV-1 with viral loads of 50 000 copies per mL or more before initiation of antiretroviral treatment. Funding National Institute of Allergy and Infectious Diseases, National Cancer Institute (National Institutes of Health, USA).
identifier
0ISSN: 1473-3099
1EISSN: 1474-4457
2DOI: 10.1016/S1473-3099(12)70037-3
3PMID: 22433279
4CODEN: LANCAO
languageeng
publisherLondon: Elsevier Ltd
subjectAcyclovir - administration & dosage ; Acyclovir - therapeutic use ; Adult ; Age ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; antiretroviral therapy ; Antiviral agents ; Antiviral Agents - administration & dosage ; Antiviral Agents - therapeutic use ; Biological and medical sciences ; CD4 antigen ; CD4 Lymphocyte Count ; Clinical trials ; Coinfection ; Data processing ; Disease Progression ; Double-Blind Method ; Female ; Herpes ; Herpes simplex ; Herpes Simplex - complications ; Herpes Simplex - drug therapy ; Herpes Simplex - virology ; Herpes simplex virus ; Herpes simplex virus 2 ; Herpesvirus 2, Human ; Herpesvirus diseases ; HIV (Viruses) ; HIV Infections - complications ; HIV Infections - drug therapy ; HIV Infections - immunology ; HIV Infections - virology ; HIV-1 ; Human immunodeficiency virus 1 ; Human viral diseases ; Humans ; Hypersensitivity ; Immunodeficiencies ; Immunodeficiencies. Immunoglobulinopathies ; Immunopathology ; Infectious Disease ; Infectious diseases ; Intention to Treat Analysis ; Kaplan-Meier Estimate ; Male ; Medical colleges ; Medical sciences ; Middle Aged ; Pharmacology. Drug treatments ; Proportional Hazards Models ; Risk assessment ; Sex ; Uganda ; Ulcers ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids ; Viral Load ; Virus diseases ; Young Adult
ispartofThe Lancet infectious diseases, 2012, Vol.12 (6), p.441-448
rights
0Elsevier Ltd
12012 Elsevier Ltd
22015 INIST-CNRS
3Copyright © 2012 Elsevier Ltd. All rights reserved.
4COPYRIGHT 2012 Elsevier B.V.
5Copyright Elsevier Limited Jun 2012
lds50peer_reviewed
oafree_for_read
citedbyFETCH-LOGICAL-1634t-485ddcdccf43ca97a00c49b1451837fa871402e416c6da69d7926e69bb690e813
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
thumbnail$$Usyndetics_thumb_exl
backlink
0$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25935754$$DView record in Pascal Francis
1$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22433279$$D View this record in MEDLINE/PubMed
search
creatorcontrib
0Reynolds, Steven J, MD
1Makumbi, Fred, PhD
2Newell, Kevin, MPH
3Kiwanuka, Noah, MBChB
4Ssebbowa, Paschal, MBChB
5Mondo, George, BSc
6Boaz, Iga, BSc
7Wawer, Maria J, Prof
8Gray, Ronald H, Prof
9Serwadda, David, Prof
10Quinn, Thomas C, Prof
title
0Effect of daily aciclovir on HIV disease progression in individuals in Rakai, Uganda, co-infected with HIV-1 and herpes simplex virus type 2: a randomised, double-blind placebo-controlled trial
1The Lancet infectious diseases
addtitleLancet Infect Dis
descriptionSummary Background Daily suppression of herpes simplex virus type 2 (HSV-2) reduces plasma HIV-1 concentrations and modestly delayed HIV-1 disease progression in one clinical trial. We investigated the effect of daily suppressive aciclovir on HIV-1 disease progression in Rakai, Uganda. Methods We did a single site, parallel, randomised, controlled trial of HIV-1, HSV-2 dually infected adults with CD4 cell counts of 300–400 cells per μL. We excluded individuals who had an AIDS-defining illness or active genital ulcer disease, and those that were taking antiretroviral therapy. Participants were randomly assigned (1:1) with computer-generated random numbers in blocks of four to receive either aciclovir 400 mg orally twice daily or placebo; participants were followed up for 24 months. All study staff and participants were masked to treatment, except for the two statisticians. The primary outcome was CD4 cell count less than 250 cells per μL or initiation of antiretroviral therapy for WHO stage 4 disease. Our intention-to-treat analysis used Cox proportional hazards models, adjusting for baseline log10 viral load, CD4 cell count, sex, and age to assess the risk of disease progression. We also investigated the effect of suppressive HSV-2 treatment stratified by baseline HIV viral load with a Cox proportional hazards model. This trial is registered with ClinicalTrials.gov , number NCT00405821. Findings 440 participants were randomly assigned, 220 to each group. 110 participants in the placebo group and 95 participants in the treatment group reached the primary endpoint (adjusted hazard ratio [HR] 0·75, 95% CI 0·58–0·99; p=0·040). 24 participants in the placebo group and 22 in the treatment group were censored, but all contributed data for the final analysis. In a subanalysis stratified by baseline HIV viral load, participants with a baseline viral load of 50 000 copies mL or more in the treatment group had a reduced HIV disease progression compared with those in the placebo group (0·62, 0·43–0·96; p=0·03). No significant difference in HIV disease progression existed between participants in the treatment group and those in the placebo group who had baseline HIV viral loads of less than 50 000 copies per mL (0·90, 0·54–1·5; p=0·688). No safety issues related to aciclovir treatment were identified. Interpretation Aciclovir reduces the rate of disease progression, with the greatest effect in individuals with a high baseline viral load. Suppressive aciclovir might be warranted for individuals dually infected with HSV-2 and HIV-1 with viral loads of 50 000 copies per mL or more before initiation of antiretroviral treatment. Funding National Institute of Allergy and Infectious Diseases, National Cancer Institute (National Institutes of Health, USA).
subject
0Acyclovir - administration & dosage
1Acyclovir - therapeutic use
2Adult
3Age
4Antibiotics. Antiinfectious agents. Antiparasitic agents
5antiretroviral therapy
6Antiviral agents
7Antiviral Agents - administration & dosage
8Antiviral Agents - therapeutic use
9Biological and medical sciences
10CD4 antigen
11CD4 Lymphocyte Count
12Clinical trials
13Coinfection
14Data processing
15Disease Progression
16Double-Blind Method
17Female
18Herpes
19Herpes simplex
20Herpes Simplex - complications
21Herpes Simplex - drug therapy
22Herpes Simplex - virology
23Herpes simplex virus
24Herpes simplex virus 2
25Herpesvirus 2, Human
26Herpesvirus diseases
27HIV (Viruses)
28HIV Infections - complications
29HIV Infections - drug therapy
30HIV Infections - immunology
31HIV Infections - virology
32HIV-1
33Human immunodeficiency virus 1
34Human viral diseases
35Humans
36Hypersensitivity
37Immunodeficiencies
38Immunodeficiencies. Immunoglobulinopathies
39Immunopathology
40Infectious Disease
41Infectious diseases
42Intention to Treat Analysis
43Kaplan-Meier Estimate
44Male
45Medical colleges
46Medical sciences
47Middle Aged
48Pharmacology. Drug treatments
49Proportional Hazards Models
50Risk assessment
51Sex
52Uganda
53Ulcers
54Viral diseases
55Viral diseases of the lymphoid tissue and the blood. Aids
56Viral Load
57Virus diseases
58Young Adult
issn
01473-3099
11474-4457
fulltexttrue
rsrctypearticle
creationdate2012
recordtypearticle
recordideNqNkmFr1TAUhosobk5_ghIQYcLtTJq0aRSUMaYbDAR1fi1pcnqXLbe5Ju3V-_P8Z57eO53uy6SFtulz3vMm582yp4weMMqqV5-ZkDznVKl9VryUlHKZ83vZLi6LXIhS3t-8b5Gd7FFKl5Qyyah4mO0UheC8kGo3-3ncdWAGEjpitfNroo0zPqxcJKEnJ6dfiXUJdAKyjGEeISWH6266rVs5O2qfps9P-kq7GTmf697qGTEhd_0kDJZ8d8PFpJQzgj_JBcQlJJLcYunhB8FOYyLDegmkeE00iciEBfa0M2LD2HrIW4_NyNJrA23ITeiHGLxH5SE67R9nDzo0AU-un3vZ-fvjL0cn-dnHD6dHh2c5q7gYclGX1hprTCe40UpqSo1QLRMlq7nsdC2ZoAUIVpnK6kpZqYoKKtW2laJQM76X7W918SC-jZCGBl0a8F73EMbUMMrrUpWV5P-BMlkVjNcS0ee30Mswxh43MlGKckZVidTBlpprDw2ebBiiNnhZWDg8EOgcrh8Wiqqq5kpgweyvgnZMrp9G1yc3vxjSXI8p_YuXW9zEkFKErllGt9BxjSYmH1WziVszZalhRbOJWzNt9Nm1-7FdgP1T9TtfCLy4BnQy2nc4XePSDVcqXspyMvDmlgHjBj24adYYyzttvNtWA85_5SA2yTjoDVgXMYONDe5Ohbe3FAyGzqHlK1hDuplJk4qGbkUmDVZsFDj_BXTdGDw
startdate2012
enddate2012
creator
0Reynolds, Steven J, MD
1Makumbi, Fred, PhD
2Newell, Kevin, MPH
3Kiwanuka, Noah, MBChB
4Ssebbowa, Paschal, MBChB
5Mondo, George, BSc
6Boaz, Iga, BSc
7Wawer, Maria J, Prof
8Gray, Ronald H, Prof
9Serwadda, David, Prof
10Quinn, Thomas C, Prof
general
0Elsevier Ltd
1Lancet Publishing Group
2Elsevier B.V
3Elsevier Limited
scope
0IQODW
1CGR
2CUY
3CVF
4ECM
5EIF
6NPM
7AAYXX
8CITATION
9BSHEE
100TZ
113V.
127QL
137RV
147U9
157X7
167XB
1788E
188AO
198C1
208C2
218FI
228FJ
238FK
24ABUWG
25BENPR
26C1K
27FYUFA
28GHDGH
29H94
30K9.
31KB0
32M0S
33M1P
34M7N
35NAPCQ
36PQEST
37PQQKQ
38PQUKI
397X8
sort
creationdate2012
titleEffect of daily aciclovir on HIV disease progression in individuals in Rakai, Uganda, co-infected with HIV-1 and herpes simplex virus type 2: a randomised, double-blind placebo-controlled trial
authorReynolds, Steven J, MD ; Makumbi, Fred, PhD ; Newell, Kevin, MPH ; Kiwanuka, Noah, MBChB ; Ssebbowa, Paschal, MBChB ; Mondo, George, BSc ; Boaz, Iga, BSc ; Wawer, Maria J, Prof ; Gray, Ronald H, Prof ; Serwadda, David, Prof ; Quinn, Thomas C, Prof
facets
frbrtype5
frbrgroupidcdi_FETCH-LOGICAL-1634t-485ddcdccf43ca97a00c49b1451837fa871402e416c6da69d7926e69bb690e813
rsrctypearticles
prefilterarticles
languageeng
creationdate2012
topic
0Acyclovir - administration & dosage
1Acyclovir - therapeutic use
2Adult
3Age
4Antibiotics. Antiinfectious agents. Antiparasitic agents
5antiretroviral therapy
6Antiviral agents
7Antiviral Agents - administration & dosage
8Antiviral Agents - therapeutic use
9Biological and medical sciences
10CD4 antigen
11CD4 Lymphocyte Count
12Clinical trials
13Coinfection
14Data processing
15Disease Progression
16Double-Blind Method
17Female
18Herpes
19Herpes simplex
20Herpes Simplex - complications
21Herpes Simplex - drug therapy
22Herpes Simplex - virology
23Herpes simplex virus
24Herpes simplex virus 2
25Herpesvirus 2, Human
26Herpesvirus diseases
27HIV (Viruses)
28HIV Infections - complications
29HIV Infections - drug therapy
30HIV Infections - immunology
31HIV Infections - virology
32HIV-1
33Human immunodeficiency virus 1
34Human viral diseases
35Humans
36Hypersensitivity
37Immunodeficiencies
38Immunodeficiencies. Immunoglobulinopathies
39Immunopathology
40Infectious Disease
41Infectious diseases
42Intention to Treat Analysis
43Kaplan-Meier Estimate
44Male
45Medical colleges
46Medical sciences
47Middle Aged
48Pharmacology. Drug treatments
49Proportional Hazards Models
50Risk assessment
51Sex
52Uganda
53Ulcers
54Viral diseases
55Viral diseases of the lymphoid tissue and the blood. Aids
56Viral Load
57Virus diseases
58Young Adult
toplevel
0peer_reviewed
1online_resources
creatorcontrib
0Reynolds, Steven J, MD
1Makumbi, Fred, PhD
2Newell, Kevin, MPH
3Kiwanuka, Noah, MBChB
4Ssebbowa, Paschal, MBChB
5Mondo, George, BSc
6Boaz, Iga, BSc
7Wawer, Maria J, Prof
8Gray, Ronald H, Prof
9Serwadda, David, Prof
10Quinn, Thomas C, Prof
collection
0Pascal-Francis
1Medline
2MEDLINE
3MEDLINE (Ovid)
4MEDLINE
5MEDLINE
6PubMed
7CrossRef
8Academic OneFile (A&I only)
9Pharma and Biotech Premium PRO
10ProQuest Central (Corporate)
11Bacteriology Abstracts (Microbiology B)
12Nursing & Allied Health Database
13Virology and AIDS Abstracts
14Health & Medical Collection
15ProQuest Central (purchase pre-March 2016)
16Medical Database (Alumni Edition)
17ProQuest Pharma Collection
18Public Health Database
19Lancet Titles
20Hospital Premium Collection
21Hospital Premium Collection (Alumni Edition)
22ProQuest Central (Alumni) (purchase pre-March 2016)
23ProQuest Central (Alumni Edition)
24ProQuest Central
25Environmental Sciences and Pollution Management
26Health Research Premium Collection
27Health Research Premium Collection (Alumni)
28AIDS and Cancer Research Abstracts
29ProQuest Health & Medical Complete (Alumni)
30Nursing & Allied Health Database (Alumni Edition)
31Health & Medical Collection (Alumni Edition)
32Medical Database
33Algology Mycology and Protozoology Abstracts (Microbiology C)
34Nursing & Allied Health Premium
35ProQuest One Academic Eastern Edition
36ProQuest One Academic
37ProQuest One Academic UKI Edition
38MEDLINE - Academic
jtitleThe Lancet infectious diseases
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
au
0Reynolds, Steven J, MD
1Makumbi, Fred, PhD
2Newell, Kevin, MPH
3Kiwanuka, Noah, MBChB
4Ssebbowa, Paschal, MBChB
5Mondo, George, BSc
6Boaz, Iga, BSc
7Wawer, Maria J, Prof
8Gray, Ronald H, Prof
9Serwadda, David, Prof
10Quinn, Thomas C, Prof
formatjournal
genrearticle
ristypeJOUR
atitleEffect of daily aciclovir on HIV disease progression in individuals in Rakai, Uganda, co-infected with HIV-1 and herpes simplex virus type 2: a randomised, double-blind placebo-controlled trial
jtitleThe Lancet infectious diseases
addtitleLancet Infect Dis
date2012
risdate2012
volume12
issue6
spage441
epage448
pages441-448
issn1473-3099
eissn1474-4457
codenLANCAO
abstractSummary Background Daily suppression of herpes simplex virus type 2 (HSV-2) reduces plasma HIV-1 concentrations and modestly delayed HIV-1 disease progression in one clinical trial. We investigated the effect of daily suppressive aciclovir on HIV-1 disease progression in Rakai, Uganda. Methods We did a single site, parallel, randomised, controlled trial of HIV-1, HSV-2 dually infected adults with CD4 cell counts of 300–400 cells per μL. We excluded individuals who had an AIDS-defining illness or active genital ulcer disease, and those that were taking antiretroviral therapy. Participants were randomly assigned (1:1) with computer-generated random numbers in blocks of four to receive either aciclovir 400 mg orally twice daily or placebo; participants were followed up for 24 months. All study staff and participants were masked to treatment, except for the two statisticians. The primary outcome was CD4 cell count less than 250 cells per μL or initiation of antiretroviral therapy for WHO stage 4 disease. Our intention-to-treat analysis used Cox proportional hazards models, adjusting for baseline log10 viral load, CD4 cell count, sex, and age to assess the risk of disease progression. We also investigated the effect of suppressive HSV-2 treatment stratified by baseline HIV viral load with a Cox proportional hazards model. This trial is registered with ClinicalTrials.gov , number NCT00405821. Findings 440 participants were randomly assigned, 220 to each group. 110 participants in the placebo group and 95 participants in the treatment group reached the primary endpoint (adjusted hazard ratio [HR] 0·75, 95% CI 0·58–0·99; p=0·040). 24 participants in the placebo group and 22 in the treatment group were censored, but all contributed data for the final analysis. In a subanalysis stratified by baseline HIV viral load, participants with a baseline viral load of 50 000 copies mL or more in the treatment group had a reduced HIV disease progression compared with those in the placebo group (0·62, 0·43–0·96; p=0·03). No significant difference in HIV disease progression existed between participants in the treatment group and those in the placebo group who had baseline HIV viral loads of less than 50 000 copies per mL (0·90, 0·54–1·5; p=0·688). No safety issues related to aciclovir treatment were identified. Interpretation Aciclovir reduces the rate of disease progression, with the greatest effect in individuals with a high baseline viral load. Suppressive aciclovir might be warranted for individuals dually infected with HSV-2 and HIV-1 with viral loads of 50 000 copies per mL or more before initiation of antiretroviral treatment. Funding National Institute of Allergy and Infectious Diseases, National Cancer Institute (National Institutes of Health, USA).
copLondon
pubElsevier Ltd
pmid22433279
doi10.1016/S1473-3099(12)70037-3
oafree_for_read