Intervention Review

You have free access to this content

Optimal time for initiation of antiretroviral therapy in asymptomatic, HIV-infected, treatment-naive adults

  1. Nandi Siegfried1,*,
  2. Olalekan A Uthman2,
  3. George W Rutherford3

Editorial Group: Cochrane HIV/AIDS Group

Published Online: 17 MAR 2010

Assessed as up-to-date: 12 NOV 2009

DOI: 10.1002/14651858.CD008272.pub2


How to Cite

Siegfried N, Uthman OA, Rutherford GW. Optimal time for initiation of antiretroviral therapy in asymptomatic, HIV-infected, treatment-naive adults. Cochrane Database of Systematic Reviews 2010, Issue 3. Art. No.: CD008272. DOI: 10.1002/14651858.CD008272.pub2.

Author Information

  1. 1

    University of Cape Town, Department of Public Health and Primary Health Care, Cape Town, South Africa

  2. 2

    University of Birmingham, WMHTAC, Public Health, Epidemiology & Biostatistics, Birmingham, UK

  3. 3

    University of California, San Francisco, Global Health Sciences, San Francisco, California, USA

*Nandi Siegfried, Department of Public Health and Primary Health Care, University of Cape Town, Cape Town, South Africa. nandi.siegfried@gmail.com.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 17 MAR 2010

SEARCH

 
Characteristics of included studies [ordered by study ID]
CIPRAHT001 2009

MethodsA single-centred trial which commenced enrollment in August 2005 in a large clinic providing HIV voluntary counseling and testing to more than 25,000 people a year in Port au Prince in Haiti. The trials was stopped early on 28 May 2009 by the Data Safety and Monitoring Board.

Follow-up took place monthly and all participants were seen by a clinician. Retention was encouraged by home visits, 24 hour/day on call clinician, free phone cards, peer counseling by people living with HIV/AIDS. Median duration of follow-up was 21 months with a range of one to 44 months.

Loss to follow-up was 4.5% (19/408) in the early ART group and 4.4% (18/408) in the deferred ART group.


Participants1,066 HIV-infected, treatment-naive adults with CD4 cell count of 200 - 350 cells/µL were referred for study screening. 150 were excluded and 816 adults were enrolled.

Inclusion criteria: HIV-infected, antiretroviral-naive, age ≥ 18 years of age, CD4 T cell count between 200 and 350 cells/µL.

Exclusion criteria: History of AIDS-defining illness, prior ART use, pregnant or breast-feeding, or needed ART in the next three months based on the judgment of the primary care clinician

Median age was 40 with males and females distributed similarly in both groups: 41% males and 59% females in the EARLY intervention group and 44% males and 56% females in the STANDARD intervention group.


InterventionsIntervention: EARLY: Start ART (lamivudine 150mg and zidovudine 300mg in a fixed-dose combination twice daily and efavirenz 600mg at night) within two weeks of enrollment.

Comparison: STANDARD: Start ART (lamivudine 150mg and zidovudine 300mg in a fixed-dose combination twice daily and efavirenz 600mg at night) when the CD4 cell count is ≤ 200 cells/µL or the patient develops an AIDS-defining illness.

Both groups received Trimethoprim-sulfamethoxazole prophylaxis and daily multi-vitamins and monthly food baskets).


OutcomesPRIMARY OUTCOME

Death - documented by one of the following: obituary, autopsy report, hospital death certificate, or contact report documenting verbal communication with the participant's healthcare provider, family member, or significant other.

SECONDARY OUTCOME

incidence of TB - HIV infected patients with a cough or other symptoms suggestive of tuberculosis are routinely screened at the clinic with a chest radiograph and three sputum smears for acid fast bacilli (AFB) by Ziehl-Neelsen staining and Mycobacterium tuberculosis culture on Lowenstein Jensen media. TB case definition was based upon American Thoracic Society with diagnosis requiring symptoms consistent with tuberculosis and microbiologic confirmation of disease, or symptoms, a chest radiograph consistent with tuberculosis, and a positive response to anti-tuberculosis therapy.

ADVERSE EVENTS

Information not presented and outstanding at current time.


NotesThe National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is the study sponsor. NIAID funded the study through the Comprehensive International Program of Research on AIDS (CIPRA). Other support came from The Global Fund Against AIDS, Tuberculosis, and Malaria, Glaxo Smith Kline, Abbott and Fondation Merieux. The trial was carried out by the Haitian Group for the Study of Kaposi's Sarcoma and Immune Deficiency Disorders (GHESKIO) Centers in Port-au-Prince, Haiti. The principal investigator is Jean William Pape, M.D., the director of the GHESKIO Centers and a professor of medicine at Weill Medical College of Cornell University in New York.

The trial was approved by the Instititional Review Board at the GHESKIO Centres in Haiti and at Cornell University (information provided Prof Dan Fitzgeral).


Risk of bias

BiasAuthors' judgementSupport for judgement

Adequate sequence generation?Low riskRandomization was by a computer-generated random numbers list in blocks of eight in a 1:1 ratio (information provided by Prof Dan Fitzgerald).

Allocation concealment?Low riskRandomization was performed by Frontier Science and Technology Research Foundation in New York (central randomization) and transmitted to the clinical site electronically (information provided by Prof Dan Fitzgerald).

Blinding?
All outcomes
High riskOpen-label and the standard (deferred) group did not receive a placebo so primary care clinicians and participants were aware of their treatment status. Investigators and members of the protocol team were blinded to the data stratified by randomization group.

Incomplete outcome data addressed?
All outcomes
Low riskAttrition was less than 5% in both intervention and comparison groups so risk of bias due to high loss to-follow-up judged as being low.

Free of selective reporting?Low riskCompares favourably with protocol on www.clinicaltrials.gov

Free of other bias?High riskStopped early but used survival analysis to overcome effects of attrition.

SMART 2008

MethodsThe trial included 318 sites in 33 countries and enrollment commenced in January 2002 and was stopped early on 10 January 2006 by the Board.

The trial compared a Viral Suppression (VS) strategy, with an experimental Drug Conservation (DC) strategy. The results for a sub-set of those participants within the larger VS-DC trial who were ARV treatment-naive are included in this review. This analysis was reported as post-hoc and included a group of participants who were either ART-naive or who had received ART and ceased to take it 6 months prior to enrollment. For this review we report the results only for those ART-naive participants.

Routine visits occurred at 1 and 2 months, every 2 months thereafter for the first year, and every 4 months in subsequent years. Visits included clinical assessments, and samples were obtained for measurement of CD4 cell count and plasma HIV RNA level. At baseline and annually, a 12-lead electrocardiogram was obtained, and data were electronically transmitted to a central reading facility for assessment of silent myocardial infarction.

Median period of follow-up was 18 months for entire RCT and for the sub-set (including those participants who had recieved ART 6 months earlier). Follow-up is not reported specifically for the ART-naive participants only. Median follow-up for the subset is reported as 15 months.


Participants5.472 HIV-infected participants with CD4 cell count > 350 cells/µL were randomly assigned to VS or DC.

Of these, 477 participants were either treatment-naive (n = 249) or had not received ART in the preceding 6 months (n = 228).

Inclusion criteria: HIV-infected, age ≥ 13 years of age, CD4 T cell count > 350 cells/µL, willing to initiate, modify, or stop antiretroviral therapy according to study guidelines.

Exclusion criteria: pregnant or breast-feeding.

Additional criteria for post-hoc sub-set analysis were that participants were antiretroviral-naive or not on treatment for greater than 6 months. We report the results for only those participants who were ART-naive.

Median age was 39 in the ART-naive Viral Suppression group and 40 years in the ART-naive Drug Conservation group. There were 27.5% females in the ART-naive VS group and 20.3% in the ART-naive DC group. Median log viral load at baseline was 4.3 copies/ml in the ART-naive VS group and 4.6 in the ART-naive DC group. Median CD4 count at baseline was 432 cells/ul in the ART-naive VS group and 441 cells/ul ART-naive DC group.


InterventionsIntervention: EARLY: In the Viral Suppression strategy available antiretroviral regimens were to be used in an uninterrupted manner with the goal of maximal and continuous suppression of HIV replication.

Comparison: DEFERRED: The Drug Conservation strategy entailed the episodic use of antiretroviral therapy according to CD4+ count thresholds: the use of antiretroviral therapy was deferred until the CD4+ count decreased to less than 250 cells per cubic millimeter, at which time antiretroviral therapy was to be initiated (or reinitiated) and continued until the CD4+ count increased to more than 350 cells per cubic millimeter. The protocol also permitted antiretroviral therapy to be initiated (or reinitiated) if symptoms of disease from HIV infection (e.g., oral thrush) developed or the percentage of CD4+ lymphocytes (CD4+ percentage) was less than 15%. On confirmation that the CD4+ count was more than 350 cells per cubic millimeter, antiretroviral therapy was to be stopped and then resumed when the CD4+ count was less than 250 cells per cubic millimeter.

The sub-set of 477 participants were those participants who were treatment-naive or not on ART for greater than 6 months. Of these 131 were ART-naive in the Viral Suppressoin Group and 118 in the Drug Conservation Group. We report the results for this group.


Outcomes
  1. Primary outcome:
    1. Death or Opportunistic Disease
  2. Secondary outcomes:
    1. Death from any cause
    2. Opportunistic Disease (fatal or non-fatal)
    3. Serious non-AIDS events (major cardiovascular, renal, or hepatic disease, and non-AIDS cancers, and deaths from non-OD causes)
    4. Composite outcome of b. and c.
  3. Adverse effects:
    1. Grade 4 adverse events (not including opportunistic disease) or death from any cause. Grade 4 adverse events were defined as potentially life-threatening symptomatic events requiring medical intervention, according to the toxicity table of the Division of AIDS of the NIAID. Data on lower-grade toxic effects were not collected.


NotesThe study was approved by the institutional review board at each site, and written informed consent was obtained from all participants.


Risk of bias

BiasAuthors' judgementSupport for judgement

Adequate sequence generation?Unclear riskStratified according to clinical site with the use of permeated blocks of random sizes. Assume computer-generated

Allocation concealment?Unclear riskAs for above

Blinding?
All outcomes
High riskInvestigators and participants were aware of treatment assignments. For primary outcome, death or Opportunistic Disease, an end-point review committee reviewed the events classification unaware of treatment assignments.

Incomplete outcome data addressed?
All outcomes
Low riskEleven were lost to follow-up of subset of 477 and median follow-up was 15 months.

Free of selective reporting?Unclear riskCompares favourably with protocol on www.clinicaltrials.gov but outcomes not clearly reported in the online protocol (possibly due to trial registration on the registry prior to World Health Organization mandatory 20 item minimum dataset criteria for prospective trial registration). We will need to contact investigators to confirm reported outcomes conform to those in protocol.

Free of other bias?High riskStopped early but acceptable statistical stopping rules applied to reduce effects of attrition bias. An O'Brien-Fleming boundary and the Lan-DeMets alpha spending function was used to determine whether to terminate the trial early. The results reported here are not free of bias as the analysis of the ART-naive was post-hoc and it is possible that other studies may not have conducted similar post-hoc analysis so there is a threat of publication bias.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Erhabor 2006Although the text of the article refers to randomizing patients, email communication with the first author confirmed that this is a stratified cohort study and not an RCT

 
Characteristics of ongoing studies [ordered by study ID]
NCT00491556

Trial name or titleEarly initiation of HAART

MethodsThis is a randomized, proof of concept study of youth 18- 24 years of age with confirmed HIV after age 9 with CD4+ T cells above 350 cells/mm3 who are randomized 3:1 to begin HAART consisting of TDF/FTC/ATV/r (preferred), AZT/3TC/ATV/r, or other recommended NRTI backbone with ATV/r upon entry or to begin treatment under current DHHS guidelines. Subjects in the experimental group who achieve virologic control by week 24 and maintain good control through 48 weeks will then de-intensify to ATV/r alone and will be followed for two years. Subjects randomized to the standard care arm will begin HAART with TDF/FTC/ATV/r (preferred), AZT/3TC/ATV/r, or other recommended ATV/r based HAART regimen according to current DHHS standard of care.

ParticipantsAge 18 yrs and 0 days to 24 yrs and 364 days with CD4+ T cells >350/mm3 as determined by two consecutive measures within 6 months of entry, with second measure being collected at pre-entry. Infected with HIV after age 9

InterventionsExperimental:

Subjects in the experimental group will begin HAART consisting of TDF/FTC/ATV/r (preferred), AZT/3TC/ATV/r or other recommended NRTI backbone with ATV/r upon entry or to begin treatment under current DHHS guidelines. Subjects in the experimental group who achieve virologic control by week 24 and maintain good control through 48 weeks will then de-intensify to ATV/r alone and will be followed for an additional two years

Control:

Subjects randomized to the standard care arm will begin HAART with TDF/FTC/ATV/r (preferred), AZT/3TC/ATV/r, or other recommended ATV/r based HAART regimen according to current DHHS standard of care and will be followed for a total of three years. Under these guidelines and under current clinical standards, subjects on the standard care arm will begin therapy when the CD4+ T cell count drops below 350 cells/mm3 or other clinical criteria necessitating treatment as determined by the site clinician occur.

OutcomesPrimary Outcome:

Ability to maintain or enhance HAART-associated quantitative changes in CD4+ T cell percentages achieved during HAART following therapy de-intensification to ATV/r in adolescents and young adults who began treatment prior to meeting DHHS guidelines.

Secondary Outcomes:

  • Quantitative and qualitative changes in T cell subsets percentage in those initiating HAART prior to current guidelines followed by de-intensification and in subjects initiating HAART by current DHHS guidelines
  • Ability to maintain decreases in T cell activation achieved during HAART following therapy de-intensification
  • Ability to maintain virologic control following de-intensification in adolescents treated with HAART prior to meeting DHHS guidelines
  • Impact of early HAART initiation on thymic output
  • Determine the emergence of drug resistance in subjects who fail therapy de-intensification
  • Evaluate the safety of initiating ART prior to significant CD4+ T cell loss with respect to emergence of drug associated toxicity and drug resistance
  • Monitor prevalence of genotypic drug resistance within an ARV naïve or minimally exposed adolescent and young adult population; evaluate the associations of subject demographic and clinical variables with presence of genotypic mutation

Starting dateOctober 2007

Contact information

Notes

START 2009

Trial name or titleStrategic Timing of Antiretroviral Treatment (START)

MethodsTreatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study

ParticipantsPatients 18 years of age and older who are infected with HIV, have CD4+ cell counts of greater than 500 cells/mm3, and who have never had antiretroviral therapy to treat HIV.

InterventionsTo determine whether initiation of ART in HIV-infected, treatment-naive persons with CD4 counts > 500 cells/mm3 is superior in terms of mortality and morbidity to deferral of treatment until the CD4 count declines to < 350 cells/mm3.

OutcomesPrimary Outcomes:

Composite endpoint of AIDS, serious non-AIDS diagnoses, and all-cause mortality

Secondary Outcomes:

  • Components of the composite primary outcome measure
  • Specific non-AIDS diagnoses
  • Adverse events
  • Hospitalization, health-care utilization, quality of life
  • HIV drug resistance and transmission risk behavior
  • Change in neurocognitive function (in a subset of participants)
  • Obtain a whole blood sample from which DNA will be extracted to study validated genetic variants that determine the risk of the various primary and secondary outcomes assessed in START (in a subset of participants)
  • Evaluate understanding of study information and satisfaction with the consent process among START participants, after receiving information from either a standard or a concise consent form (at a subset of sites)
  • Large and small artery elasticity (in a subset of participants)

Starting dateMarch 2009

Contact informationUniversity of Minnesota (James D. Neaton, Ph.D/Principal Investigator)

NotesNCT00867048

 
Comparison 1. Early ART versus standard or deferred ART (CD4 ≤ 200 or CD4 ≤ 250 cells/µl)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Death21065Risk Ratio (M-H, Random, 95% CI)0.26 [0.11, 0.62]

 2 Tuberculosis21065Risk Ratio (M-H, Random, 95% CI)0.54 [0.26, 1.12]

 3 Disease progression measured by opportunistic disease1Risk Ratio (M-H, Random, 95% CI)Totals not selected

 4 Any Grade 3 or 4 adverse events ITT analysis1Risk Ratio (M-H, Random, 95% CI)Totals not selected

 5 Grade 3 or 4 anaemia Per Protocol analysis1Risk Ratio (M-H, Random, 95% CI)Totals not selected

 
Summary of findings for the main comparison. Early ART versus standard or deferred ART (CD4 <= 200 or CD4 <= 250 cells/µl) for asymptomatic, HIV-infected, treatment naive adults

Early ART versus standard or deferred ART (CD4 ⤠200 or CD4 ⤠250 cells/µl) for asymptomatic, HIV-infected, treatment naive adults

Patient or population: patients with asymptomatic, HIV-infected, treatment naive adults
Settings:
Intervention: Early ART versus standard or deferred ART (CD4 ⤠200 or CD4 ⤠250 cells/µl)

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlEarly ART versus standard or deferred ART (CD4 ⤠200 or CD4 ⤠250 cells/µl)

DeathStudy populationRR 0.26
(0.11 to 0.62)
1065
(2 studies)
⊕⊕⊕⊝
moderate1,2

46 per 100012 per 1000
(5 to 29)

Medium risk population

32 per 10008 per 1000
(4 to 20)

TuberculosisStudy populationRR 0.54
(0.26 to 1.12)
1065
(2 studies)
⊕⊕⊕⊝
moderate1,2

68 per 100037 per 1000
(18 to 76)

Medium risk population

44 per 100024 per 1000
(11 to 49)

Disease progression measured by opportunistic disease
Opportunistic disease events
Follow-up: mean 18 months
Study populationOR 0.29
(0.03 to 2.87)
249
(1 study)
⊕⊕⊝⊝
low1,2,3

25 per 10007 per 1000
(1 to 69)

Medium risk population

25 per 10007 per 1000
(1 to 69)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 The SMART study is a post hoc analysis of a sub-set of a larger trial
2 As the SMART sub-set is a post hoc analysis there may be other trials which did not conduct or publish similar analyses of potential sub-sets within the original trials. This is a form of publication bias and we have therefore downgraded the results accordingly
3 This result is a post hoc subset analysis from only one trial and the evidence is therefore not directly able to answer the outcome of disease progression
 
Table 1. Search methods for PUBMED

IDSearchHits

#5Search #1 AND #2 AND #3 AND #4 Limits: Publication Date from 1996 to 2009 1389

#4Search "THERAPY INITIATION" OR "TREATMENT INITIATION" OR "DRUG THERAPY INITIATION" OR"WHEN TO START" OR "EARLY INITIATION" OR DRUG ADMINISTRATION SCHEDULE[MeSH Terms] OR "DRUG ADMINISTRATION SCHEDULE"71826

#3Search Antiretroviral Therapy, Highly Active[MeSH] OR Anti-Retroviral Agents[MeSH] OR Antiviral Agents[MeSH:NoExp] OR ((anti) AND (hiv[tw])) OR antiretroviral*[tw] OR ((anti) AND (retroviral*[tw])) OR HAART[tw] OR ((anti) AND (acquired immunodeficiency[tw])) OR ((anti) AND (acquired immunedeficiency[tw])) OR ((anti) AND (acquired immuno-deficiency[tw])) OR ((anti) AND (acquired immune-deficiency[tw])) OR ((anti) AND (acquired immun*) AND (deficiency[tw]))99790

#2Search (HIV Infections[MeSH] OR HIV[MeSH] OR hiv[tw] OR hiv-1*[tw] OR hiv-2*[tw] OR hiv1[tw] OR hiv2[tw] OR hiv infect*[tw] OR human immunodeficiency virus[tw] OR human immunedeficiency virus[tw] OR human immuno-deficiency virus[tw] OR human immune-deficiency virus[tw] OR ((human immun*) AND (deficiency virus[tw])) OR acquired immunodeficiency syndrome[tw] OR acquired immunedeficiency syndrome[tw] OR acquired immuno-deficiency syndrome[tw] OR acquired immune-deficiency syndrome[tw] OR ((acquired immun*) AND (deficiency syndrome[tw])) OR "sexually transmitted diseases, viral"[MESH:noexp])247596

#1Search randomized controlled trial [pt] OR controlled clinical trial [pt] OR randomized controlled trials [mh] OR random allocation [mh] OR double-blind method [mh] OR single-blind method [mh] OR clinical trial [pt] OR clinical trials [mh] OR ("clinical trial" [tw]) OR ((singl* [tw] OR doubl* [tw] OR trebl* [tw] OR tripl* [tw]) AND (mask* [tw] OR blind* [tw])) OR ( placebos [mh] OR placebo* [tw] OR random* [tw] OR research design [mh:noexp] OR comparative study [mh] OR evaluation studies [mh] OR follow-up studies [mh] OR prospective studies [mh] OR control* [tw] OR prospectiv* [tw] OR volunteer* [tw]) NOT (animals [mh] NOT human [mh])3130518

 
Table 2. Search methods for EMBASE

IDSearchHits

#5#1 AND #2 AND #3 AND #4838

#4random*:ti OR random*:ab OR factorial*:ti OR factorial*:ab OR cross?over*:ti OR cross?over:ab OR crossover*:ti OR crossover*:ab OR placebo*:ti OR placebo*:ab OR (doubl*:ti AND blind*:ti) OR (doubl*:ab AND blind*:ab) OR (singl*:ti AND blind*:ti) OR (singl*:ab AND blind*:ab) OR assign*:ti OR assign*:ab OR volunteer*:ti OR volunteer*:ab OR 'crossover procedure'/exp OR 'double-blind procedure'/exp OR 'single-blind procedure'/exp OR 'randomized controlled trial'/exp OR allocat*:ti OR allocat*:ab AND [1990-2009]/py751,259

#3'drug administration schedule'/exp OR 'when to start' OR 'drug therapy initiation' OR 'treatment initiation' OR 'therapy initiation' AND [1990-2009/py478,436

#2'human immunodeficiency virus vaccine'/exp OR 'anti human immunedeficiency':ti OR 'anti human immunedeficiency':ab OR 'anti human immunodeficiency':ti OR 'anti human immunodeficiency':ab OR 'anti human immuno-deficiency':ti OR 'anti human immuno-deficiency':ab OR 'anti human immune-deficiency':ti OR 'anti human immune-deficiency':ab OR 'anti acquired immune-deficiency':ti OR 'anti acquired immune-deficiency':ab OR 'anti acquired immunedeficiency':ti OR 'anti acquired immunedeficiency':ab OR 'anti acquired immunodeficiency':ti OR 'anti acquired immunodeficiency':ab OR 'anti acquired immuno-deficiency':ti OR 'anti acquired immuno-deficiency':ab OR 'anti hiv':ti OR 'anti hiv':ab OR antiretrovir*:ti OR antiretrovir*:ab OR 'anti retroviral':ti OR 'anti retroviral':ab OR 'anti retrovirals':ti OR 'anti retrovirals':ab OR 'anti retrovirus':ti OR 'anti retrovirus':ab OR haart:ti OR haart:ab OR 'aids vaccine':ti OR 'aids vaccine':ab OR 'aids vaccines':ti OR 'aids vaccines':ab OR 'anti human immunodeficiency virus agent'/exp OR 'antiretrovirus agent'/exp OR 'antivirus agent'/exp OR 'highly active antiretroviral therapy'/exp AND [1990-2009]/py369,711

#1'human immunodeficiency virus infection'/exp OR 'human immunodeficiency virus'/exp OR 'b cell lymphoma'/exp OR hiv:ti OR hiv:ab OR 'hiv-1':ti OR 'hiv-1':ab OR 'hiv-2':ti OR 'hiv-2':ab OR 'human immunodeficiency virus':ti OR 'human immunodeficiency virus':ab OR 'human immunedeficiency virus':ti OR 'human immunedeficiency virus':ab OR 'human immune-deficiency virus':ti OR 'human immune-deficiency virus':ab OR 'human immuno-deficiency virus':ti OR 'human immuno-deficiency virus':ab OR 'acquired immunodeficiency syndrome':ti OR 'acquired immunodeficiency syndrome':ab OR 'acquired immuno-deficiency syndrome':ti OR 'acquired immuno-deficiency syndrome':ab OR 'acquired immune-deficiency syndrome':ti OR 'acquired immune-deficiency syndrome':ab OR 'acquired immunedeficiency syndrome':ti OR 'acquired immunedeficiency syndrome':ab AND [1990-2009]/py275,043

 
Table 3. Search methods for CENTRAL

IDSearchHits

#1(HIV INFECTIONS) OR HIV OR HIV OR HIV-1* OR HIV-2* OR HIV1 OR HIV2 OR (HIV INFECT*) OR (HUMAN IMMUNODEFICIENCY VIRUS) OR (HUMAN IMMUNEDEFICIENCY VIRUS) OR (HUMAN IMMUNO-DEFICIENCY VIRUS) OR (HUMAN IMMUNE-DEFICIENCY VIRUS) OR ((HUMAN IMMUN*) AND (DEFICIENCY VIRUS)) OR (ACQUIRED IMMUNODEFICIENCY SYNDROME) OR (ACQUIRED IMMUNEDEFICIENCY SYNDROME) OR (ACQUIRED IMMUNO-DEFICIENCY SYNDROME) OR (ACQUIRED IMMUNE-DEFICIENCY SYNDROME) OR ((ACQUIRED IMMUN*) AND (DEFICIENCY SYNDROME)) OR (VIRAL SEXUALLY TRANSMITTED DISEASES), from 1996 to 20096956

#2"THERAPY INITIATION" OR "TREATMENT INITIATION" OR "DRUG THERAPY INITIATION" OR "WHEN TO START" OR "EARLY INITIATION" OR DRUG ADMINISTRATION SCHEDULE", from 1996 to 200914455

#3"Highly Active Antiretroviral Therapy" OR "Anti-Retroviral Agents" OR ((anti) AND (hiv)) OR antiretroviral* OR ((anti) AND (retroviral*)) OR HAART OR ((anti) AND (acquired immunodeficiency)) OR ((anti) AND (acquired immunedeficiency)) OR ((anti) AND (acquired immuno-deficiency)) OR ((anti) AND (acquired immune-deficiency)) OR ((anti) AND (acquired immun*) AND (deficiency)), from 1996 to 20093092

#4(#1 AND #2 AND #3)424

 
Table 4. Search methods for NLM Gateway

Search
Number
SearchItems
Found

#10 Search: #8 AND #92666*

#9 Search: Antiretroviral Therapy, Highly Active[MeSH] OR Anti-Retroviral Agents[MeSH] OR Antiviral Agents[MeSH:NoExp] OR ((anti) AND (hiv[tw])) OR antiretroviral*[tw] OR ((anti) AND (retroviral*[tw])) OR HAART[tw] OR ((anti) AND (acquired immunodeficiency[tw])) OR ((anti) AND (acquired immunedeficiency[tw])) OR ((anti) AND (acquired immuno-deficiency[tw])) OR ((anti) AND (acquired immune-deficiency[tw])) OR ((anti) AND (acquired immun*) AND (deficiency[tw]))123249 

#8 Search: #1 AND #73599 

#7 Search: #2 OR #3 OR #4 OR #5 OR #686724 

#6 Search: DRUG ADMINISTRATION SCHEDULE[MeSH] OR "DRUG ADMINISTRATION SCHEDULE"70915 

#5 Search: "WHEN TO START"12948 

#4 Search: "DRUG THERAPY INITIATION"126 

#3 Search: "TREATMENT INITIATION"2581 

#2 Search: "THERAPY INITIATION"1710 

#1 Search: ((HIV Infections[MeSH] OR HIV[MeSH] OR hiv[tw] OR hiv-1*[tw] OR hiv-2*[tw] OR hiv1[tw] OR hiv2[tw] OR hiv infect*[tw] OR human immunodeficiency virus[tw] OR human immunedeficiency virus[tw] OR human immuno-deficiency virus[tw] OR human immune-deficiency virus[tw] OR ((human immun*) AND (deficiency virus[tw])) OR acquired immunodeficiency syndrome[tw] )) OR ((acquired immunedeficiency syndrome[tw] OR acquired immuno-deficiency syndrome[tw] OR acquired immune-deficiency syndrome[tw] OR ((acquired immun*) AND (deficiency syndrome[tw])) OR "sexually transmitted diseases, viral"[MESH:noexp]))352167 

 * Of the 2666 records, 94 were identified as Meeting Abstracts and these were the records searched.