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CompletedNCT01075152COATUpdated Jun 9, 2020Results posted

Cryptococcal Optimal ART Timing Trial

A Phase 4 interventional study of efavirenz and nucleoside in Cryptococcal Meningitis, HIV Infections and AIDS, sponsored by University of Minnesota. Completed at 3 sites in 2 countries. Open to participants aged 14 Years and older. Per ClinicalTrials.gov, last updated 2020-06-09.

Sponsored by University of Minnesota · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
177
Allocation
Randomized
Ages
14 Years and older
Sex
All
01

Study summary

The Cryptococcal Optimal ART Timing (COAT) trial seeks to determine after cryptococcal meningitis (CM) whether early initiation of antiretroviral therapy (ART) prior to hospital discharge results in superior survival compared to standard initiation of ART started as an outpatient.

Read the detailed description

After 7-11 days of amphotericin B therapy, subjects will be randomized in a 1:1 allocation to:

  • Early initiation of ART (Experimental Group) = ART initiated within 48 hours after study entry, OR
  • Standard initiation of ART (Control Group) = ART at >=4 weeks after study entry

HIV therapy will be with efavirenz plus nucleoside backbone per national guidelines for first line therapy.

02

Conditions studied

  • Cryptococcal Meningitis
  • HIV Infections
  • AIDS

Keywords

  • cryptococcal meningitis
  • cryptococcus
  • cryptococcosis
  • HIV
  • AIDS
  • strategy
03

Who can participate

Ages eligible
14 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • HIV-infection, documented by ELISA
  • Antiretroviral medication naïve (excluding mother-to-child transmission therapy)
  • Age >14 years
  • Cryptococcal meningitis diagnosed by either culture or CSF cryptococcal antigen (CRAG)
  • Ability and willingness of the participant or legal guardian/representative to give informed consent.
  • Receiving amphotericin-based anti-fungal therapy

Exclusion criteria

Exclusion Criteria:

  • Study entry prior to receipt of \<7 days or >11 days of amphotericin therapy
  • History of prior, known cryptococcal meningitis
  • Inability to take enteral medication
  • Receiving chemotherapy or other immunosuppressant medications
  • Cannot or unlikely to attend regular clinic visits
  • Contraindication to immediate or delayed HIV therapy based on serious co-morbidities or co-infections, or laboratory values
  • Pregnancy or Breastfeeding
  • Female participants of childbearing potential who are participating in sexual activity that could lead to pregnancy must agree to use two reliable methods of contraception
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
177 participants (actual)

Study arms

  • Experimental
    Earlier HIV Therapy

    HIV therapy initiated at 7-13 days of cryptococcal meningitis diagnosis. HIV therapy consisting of a nucleoside with lamivudine and efavirenz.

    Drug: efavirenz · Biological: nucleoside

  • Active comparator
    Deferred HIV Therapy

    HIV therapy initiated at 5 weeks after cryptococcal meningitis diagnosis (+/- 1 week). HIV therapy consisting of a nucleoside with lamivudine and efavirenz.

    Drug: efavirenz · Biological: nucleoside

Interventions

  • Drugefavirenz

    Treatment strategy of when to initiate first line HIV therapy after cryptococcal meningitis diagnosis.

    Also known as: sustiva

  • Biologicalnucleoside

    Treatment strategy of when to initiate first line HIV therapy after cryptococcal meningitis diagnosis.

    Also known as: zidovudine or stavudine, lamivudine

05

What researchers measure

Primary outcomes

  1. Mortality

    Intention to treat analysis of 26 week survival of all subjects enrolled. Reported below are the numbers of participants who died by Week 26.

    Time frame: 26 weeks from study entry

Secondary outcomes

  1. Incidence of Immune Reconstitution Inflammatory Syndrome

    Incidence of cryptococcal-related immune reconstitution inflammatory syndrome through 46 weeks after enrollment.

    Time frame: 46 weeks

  2. Incidence of Cryptococcal-relapse

    Incidence of culture positive cryptococcal meningitis relapse

    Time frame: 46 weeks

  3. Safety of ART Initiation

    Incidence of Adverse Events (Grade 3,4,5) through 46-weeks, as defined by the National Institute of Allergy and Infectious Diseases, Division of AIDS toxicity classification scale, version 2009.

    Time frame: 46 weeks

  4. 46-week Survival

    46-week survival by time-to-event analysis of all subjects enrolled

    Time frame: 46 weeks

  5. HIV-1 Viral Suppression

    HIV-1 virologic suppression to \<400 copies/mL at 26-weeks after enrollment

    Time frame: 26 weeks

  6. Antiretroviral Therapy Tolerability

    Incidence of antiretroviral therapy interruption by \>=3 consecutive days

    Time frame: 26 weeks

  7. Karnofsky Functional Status

    Functional status via Karnofsky performance status score at 4, 26, 46 weeks. Karnofsky Scale: 100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of his personal needs. 50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent. 20 - Very sick; hospital admission necessary; active supportive treatment necessary. 10 - Moribund; fatal processes progressing rapidly. 0 - Dead

    Time frame: 46 weeks

  8. Microbiologic Clearance

    Microbiologic clearance of cryptococcus as measured by serial quantitative cryptococcal cultures collected at diagnosis through 14 days of amphotericin therapy. The early fungicidal activity (EFA) of the rate of clearance is expressed as log10 colony forming units (CFU) of Cryptococcus neoformans per mL of CSF per day.

    Time frame: 4 weeks

Other outcomes

  1. Percentage of Participants, Per CSF WBC Subgroup, Who Died by Week 26

    Percentage of Participants who died by week 26 based on CSF white blood cell (WBC) count at study entry (time of randomization at a median of 8 days of anti-fungal therapy).

    Time frame: 26 weeks

06

Results

Posted Aug 20, 2014
Limitations and caveats
The differences in mortality in the two arms were of sufficient magnitude that trial enrollment was stopped early by the Data and Safety Monitoring Board. Historically, trials stopped early routinely over-estimate the magnitude of benefit or harm.

Participant flow

Participant flow — Overall Study
MilestoneEarlier HIV TherapyDeferred HIV Therapy
Started8889
Completed8789
Not completed10
Withdrew: Withdrawal by subject10

Outcome measures

PrimaryMortality

Intention to treat analysis of 26 week survival of all subjects enrolled. Reported below are the numbers of participants who died by Week 26.

Time frame:
26 weeks from study entry
Reported as:
Number · participants
Mortality
participantsEarlier HIV TherapyDeferred HIV Therapy
Mortality4027
Statistical analysis
  • Earlier HIV Therapy vs Deferred HIV Therapy · Regression, Cox · p = 0.03 (A Lan-DeMets spending function analog of the O'Brien-Fleming boundaries was proposed to control the type-I error resulting from multiple interim analyses.) · Hazard ratio (hr): 1.73 · 95% CI 1.06 to 2.82Hazard Ratio describes the risk of earlier HIV therapy in comparison to deferred HIV therapy initiation as the reference group.
SecondaryIncidence of Immune Reconstitution Inflammatory Syndrome

Incidence of cryptococcal-related immune reconstitution inflammatory syndrome through 46 weeks after enrollment.

Time frame:
46 weeks
Reported as:
Number · participants
Incidence of Immune Reconstitution Inflammatory Syndrome
participantsEarlier HIV TherapyDeferred HIV Therapy
Incidence of Immune Reconstitution Inflammatory Syndrome179
Statistical analysis
  • Earlier HIV Therapy vs Deferred HIV Therapy · Gray's method of cumulative incidence · p = 0.32
SecondaryIncidence of Cryptococcal-relapse

Incidence of culture positive cryptococcal meningitis relapse

Time frame:
46 weeks
Reported as:
Number · participants
Incidence of Cryptococcal-relapse
participantsEarlier HIV TherapyDeferred HIV Therapy
Incidence of Cryptococcal-relapse28
Statistical analysis
  • Earlier HIV Therapy vs Deferred HIV Therapy · Gray's method of cumulative incidence · p = 0.06
SecondarySafety of ART Initiation

Incidence of Adverse Events (Grade 3,4,5) through 46-weeks, as defined by the National Institute of Allergy and Infectious Diseases, Division of AIDS toxicity classification scale, version 2009.

Time frame:
46 weeks
Reported as:
Number · participants
Safety of ART Initiation
participantsEarlier HIV TherapyDeferred HIV Therapy
Safety of ART Initiation7375
Statistical analysis
  • Earlier HIV Therapy vs Deferred HIV Therapy · Fisher Exact · p = 0.98
Secondary46-week Survival

46-week survival by time-to-event analysis of all subjects enrolled

Time frame:
46 weeks
Reported as:
Number · participants
46-week Survival
participantsEarlier HIV TherapyDeferred HIV Therapy
46-week Survival4129
Statistical analysis
  • Earlier HIV Therapy vs Deferred HIV Therapy · Regression, Cox · p = 0.04 · Hazard ratio (hr): 1.66 · 95% CI 1.03 to 2.68
SecondaryHIV-1 Viral Suppression

HIV-1 virologic suppression to \<400 copies/mL at 26-weeks after enrollment

Time frame:
26 weeks
Reported as:
Number · participants
HIV-1 Viral Suppression
participantsEarlier HIV TherapyDeferred HIV Therapy
HIV-1 Viral Suppression4349
Statistical analysis
  • Earlier HIV Therapy vs Deferred HIV Therapy · Fisher Exact · p = 0.26
SecondaryAntiretroviral Therapy Tolerability

Incidence of antiretroviral therapy interruption by \>=3 consecutive days

Time frame:
26 weeks
Reported as:
Number · participants
Antiretroviral Therapy Tolerability
participantsEarlier HIV TherapyDeferred HIV Therapy
Antiretroviral Therapy Tolerability51
Statistical analysis
  • Earlier HIV Therapy vs Deferred HIV Therapy · Fisher Exact · p = 0.23
SecondaryKarnofsky Functional Status

Functional status via Karnofsky performance status score at 4, 26, 46 weeks. Karnofsky Scale: 100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of his personal needs. 50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent. 20 - Very sick; hospital admission necessary; active supportive treatment necessary. 10 - Moribund; fatal processes progressing rapidly. 0 - Dead

Time frame:
46 weeks
Reported as:
Mean · Scores on a scale
Karnofsky Functional Status
Scores on a scaleEarlier HIV TherapyDeferred HIV Therapy
4 weeks70 ± 1970 ± 19
26 weeks93 ± 793 ± 10
46 weeks92 ± 1095 ± 8
Statistical analysis
  • Earlier HIV Therapy vs Deferred HIV Therapy · repeated measure analysis · p = 0.34
SecondaryMicrobiologic Clearance

Microbiologic clearance of cryptococcus as measured by serial quantitative cryptococcal cultures collected at diagnosis through 14 days of amphotericin therapy. The early fungicidal activity (EFA) of the rate of clearance is expressed as log10 colony forming units (CFU) of Cryptococcus neoformans per mL of CSF per day.

Time frame:
4 weeks
Reported as:
Mean · log10 CFU/mL/day
Microbiologic Clearance
log10 CFU/mL/dayEarlier HIV TherapyDeferred HIV Therapy
EFA by mixed effects model-0.31 (-0.34 to -0.28)-0.31 (-0.34 to -0.28)
EFA by linear regression-0.39 (-0.45 to -0.32)-0.35 (-0.39 to -0.31)
Statistical analysis
  • Earlier HIV Therapy vs Deferred HIV Therapy · Regression, Linear · p = 0.44a linear mixed effects regression model fit with a random intercept and slope estimated the rate of clearance
Other pre-specifiedPercentage of Participants, Per CSF WBC Subgroup, Who Died by Week 26

Percentage of Participants who died by week 26 based on CSF white blood cell (WBC) count at study entry (time of randomization at a median of 8 days of anti-fungal therapy).

Time frame:
26 weeks
Reported as:
Number · percentage of participants
Percentage of Participants, Per CSF WBC Subgroup, Who Died by Week 26
percentage of participantsEarlier HIV TherapyDeferred HIV Therapy
CSF WBC <5 /mcl (n=33, 31)48.516.1
CSF WBC >5/mcL (n=42, 40)40.545
Statistical analysis
  • Earlier HIV Therapy vs Deferred HIV Therapy · Regression, Cox · p = 0.02 (This is the interaction p-value for CSF white cell count at randomization (implying there is a statistical difference in the outcome by arm based on this parameter).)

Adverse events

Collected over 46 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Earlier HIV Therapy—49/88 (55.7%)73/88 (83%)
Deferred HIV Therapy—53/89 (59.6%)75/89 (84.3%)
Most frequent serious events
Most frequent serious events
EventEarlier HIV TherapyDeferred HIV Therapy
Grade 4 Serious AEsNervous system disorders38/8842/89
Grade 3 Serious AEsNervous system disorders40/8838/89
Grade 5 AEsNervous system disorders11/885/89
Most frequent other events
Most frequent other events
EventEarlier HIV TherapyDeferred HIV Therapy
HematologyBlood and lymphatic system disorders41/8847/89
ChemistriesMetabolism and nutrition disorders32/8825/89
InfectionInfections and infestations10/8818/89

Baseline characteristics

HIV-infected persons not previously receiving HIV therapy with first episode of cryptococcal meningitis diagnosed by CSF culture and/or CSF cryptococcal antigen testing.

Age, Continuous
Age, Continuous(years)Earlier HIV TherapyDeferred HIV TherapyTotal
Median35 (28 to 40)36 (30 to 40)35 (29 to 40)
Sex: Female, Male
Sex: Female, Male(Participants)Earlier HIV TherapyDeferred HIV TherapyTotal
Female424284
Male464793
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Earlier HIV TherapyDeferred HIV TherapyTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American8889177
White000
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Earlier HIV TherapyDeferred HIV TherapyTotal
Uganda7577152
South Africa131225
CD4 Count, baseline
CD4 Count, baseline(cells/mcL)Earlier HIV TherapyDeferred HIV TherapyTotal
Median19 (9 to 69)28 (11 to 76)23 (10 to 73)
CSF Quantitative Culture, baseline
CSF Quantitative Culture, baseline(log10 colony forming units/mL of CSF)Earlier HIV TherapyDeferred HIV TherapyTotal
Median5.3 (4.2 to 5.7)4.8 (3.8 to 5.5)5.1 (4.0 to 5.6)
CSF Cryptococcal Antigen titer, 1:xxxx
CSF Cryptococcal Antigen titer, 1:xxxx(titers)Earlier HIV TherapyDeferred HIV TherapyTotal
Median8000 (2000 to 16000)4000 (1000 to 14400)6400 (2000 to 16000)
HIV-1 Viral Load
HIV-1 Viral Load(log10 copies/mL)Earlier HIV TherapyDeferred HIV TherapyTotal
Median5.5 (5.2 to 5.8)5.5 (5.3 to 5.8)5.5 (5.2 to 5.8)
07

Study locations

3 sites
  • GF Jooste Hospital
    Cape Town, South Africa
  • Infectious Disease Institute, Mulago Hospital, Makerere University
    Kampala, Uganda
  • Mbarara University of Science and Technology
    Mbarara, Uganda
08

References and documents

Publications

  • Rajasingham R, Williams D, Meya DB, Meintjes G, Boulware DR, Scriven J. Nosocomial drug-resistant bacteremia in 2 cohorts with cryptococcal meningitis, Africa. Emerg Infect Dis. 2014 Apr;20(4):722-4. doi: 10.3201/eid2004.131277. No abstract available. PubMed 24655747 ↗
  • Carlson RD, Rolfes MA, Birkenkamp KE, Nakasujja N, Rajasingham R, Meya DB, Boulware DR. Predictors of neurocognitive outcomes on antiretroviral therapy after cryptococcal meningitis: a prospective cohort study. Metab Brain Dis. 2014 Jun;29(2):269-279. doi: 10.1007/s11011-013-9476-1. Epub 2014 Jan 9. PubMed 24399496 ↗
  • Boulware DR, Rolfes MA, Rajasingham R, von Hohenberg M, Qin Z, Taseera K, Schutz C, Kwizera R, Butler EK, Meintjes G, Muzoora C, Bischof JC, Meya DB. Multisite validation of cryptococcal antigen lateral flow assay and quantification by laser thermal contrast. Emerg Infect Dis. 2014 Jan;20(1):45-53. doi: 10.3201/eid2001.130906. PubMed 24378231 ↗
  • Kabanda T, Siedner MJ, Klausner JD, Muzoora C, Boulware DR. Point-of-care diagnosis and prognostication of cryptococcal meningitis with the cryptococcal antigen lateral flow assay on cerebrospinal fluid. Clin Infect Dis. 2014 Jan;58(1):113-6. doi: 10.1093/cid/cit641. Epub 2013 Sep 24. PubMed 24065327 ↗
  • Robertson EJ, Najjuka G, Rolfes MA, Akampurira A, Jain N, Anantharanjit J, von Hohenberg M, Tassieri M, Carlsson A, Meya DB, Harrison TS, Fries BC, Boulware DR, Bicanic T. Cryptococcus neoformans ex vivo capsule size is associated with intracranial pressure and host immune response in HIV-associated cryptococcal meningitis. J Infect Dis. 2014 Jan 1;209(1):74-82. doi: 10.1093/infdis/jit435. Epub 2013 Aug 14. PubMed 23945372 ↗
  • Durski KN, Kuntz KM, Yasukawa K, Virnig BA, Meya DB, Boulware DR. Cost-effective diagnostic checklists for meningitis in resource-limited settings. J Acquir Immune Defic Syndr. 2013 Jul 1;63(3):e101-8. doi: 10.1097/QAI.0b013e31828e1e56. PubMed 23466647 ↗
  • Rajasingham R, Rolfes MA, Birkenkamp KE, Meya DB, Boulware DR. Cryptococcal meningitis treatment strategies in resource-limited settings: a cost-effectiveness analysis. PLoS Med. 2012;9(9):e1001316. doi: 10.1371/journal.pmed.1001316. Epub 2012 Sep 25. PubMed 23055838 ↗
  • Rolfes MA, Hullsiek KH, Rhein J, Nabeta HW, Taseera K, Schutz C, Musubire A, Rajasingham R, Williams DA, Thienemann F, Muzoora C, Meintjes G, Meya DB, Boulware DR. The effect of therapeutic lumbar punctures on acute mortality from cryptococcal meningitis. Clin Infect Dis. 2014 Dec 1;59(11):1607-14. doi: 10.1093/cid/ciu596. Epub 2014 Jul 23. Erratum In: Clin Infect Dis. 2015 May 1;60(9):1449. doi: 10.1093/cid/civ134. PubMed 25057102 ↗
  • Scriven JE, Rhein J, Hullsiek KH, von Hohenberg M, Linder G, Rolfes MA, Williams DA, Taseera K, Meya DB, Meintjes G, Boulware DR; COAT Team. Early ART After Cryptococcal Meningitis Is Associated With Cerebrospinal Fluid Pleocytosis and Macrophage Activation in a Multisite Randomized Trial. J Infect Dis. 2015 Sep 1;212(5):769-78. doi: 10.1093/infdis/jiv067. Epub 2015 Feb 4. PubMed 25651842 ↗
  • Williams DA, Kiiza T, Kwizera R, Kiggundu R, Velamakanni S, Meya DB, Rhein J, Boulware DR. Evaluation of fingerstick cryptococcal antigen lateral flow assay in HIV-infected persons: a diagnostic accuracy study. Clin Infect Dis. 2015 Aug 1;61(3):464-7. doi: 10.1093/cid/civ263. Epub 2015 Apr 1. PubMed 25838287 ↗
  • Rajasingham R, Rhein J, Klammer K, Musubire A, Nabeta H, Akampurira A, Mossel EC, Williams DA, Boxrud DJ, Crabtree MB, Miller BR, Rolfes MA, Tengsupakul S, Andama AO, Meya DB, Boulware DR. Epidemiology of meningitis in an HIV-infected Ugandan cohort. Am J Trop Med Hyg. 2015 Feb;92(2):274-9. doi: 10.4269/ajtmh.14-0452. Epub 2014 Nov 10. PubMed 25385864 ↗
  • Nabeta HW, Bahr NC, Rhein J, Fossland N, Kiragga AN, Meya DB, Dunlop SJ, Boulware DR. Accuracy of noninvasive intraocular pressure or optic nerve sheath diameter measurements for predicting elevated intracranial pressure in cryptococcal meningitis. Open Forum Infect Dis. 2014 Oct 11;1(3):ofu093. doi: 10.1093/ofid/ofu093. eCollection 2014 Dec. PubMed 25734161 ↗
  • Meya DB, Okurut S, Zziwa G, Rolfes MA, Kelsey M, Cose S, Joloba M, Naluyima P, Palmer BE, Kambugu A, Mayanja-Kizza H, Bohjanen PR, Eller MA, Wahl SM, Boulware DR, Manabe YC, Janoff EN. Cellular immune activation in cerebrospinal fluid from ugandans with cryptococcal meningitis and immune reconstitution inflammatory syndrome. J Infect Dis. 2015 May 15;211(10):1597-606. doi: 10.1093/infdis/jiu664. Epub 2014 Dec 9. PubMed 25492918 ↗
  • Bahr NC, Rolfes MA, Musubire A, Nabeta H, Williams DA, Rhein J, Kambugu A, Meya DB, Boulware DR. Standardized electrolyte supplementation and fluid management improves survival during amphotericin therapy for cryptococcal meningitis in resource-limited settings. Open Forum Infect Dis. 2014 Aug 25;1(2):ofu070. doi: 10.1093/ofid/ofu070. eCollection 2014 Sep. PubMed 25734140 ↗
  • Kwizera R, Nguna J, Kiragga A, Nakavuma J, Rajasingham R, Boulware DR, Meya DB. Performance of cryptococcal antigen lateral flow assay using saliva in Ugandans with CD4 <100. PLoS One. 2014 Jul 31;9(7):e103156. doi: 10.1371/journal.pone.0103156. eCollection 2014. PubMed 25078453 ↗
  • Boulware DR, Meya DB, Muzoora C, Rolfes MA, Huppler Hullsiek K, Musubire A, Taseera K, Nabeta HW, Schutz C, Williams DA, Rajasingham R, Rhein J, Thienemann F, Lo MW, Nielsen K, Bergemann TL, Kambugu A, Manabe YC, Janoff EN, Bohjanen PR, Meintjes G; COAT Trial Team. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med. 2014 Jun 26;370(26):2487-98. doi: 10.1056/NEJMoa1312884. PubMed 24963568 ↗
  • Kwizera R, Sadiq A, Ndyetukira JF, Nalintya E, Williams D, Rhein J, Boulware DR, Meya DB; COAT and ASTRO trial teams. Impact of community engagement and social support on the outcomes of HIV-related meningitis clinical trials in a resource-limited setting. Res Involv Engagem. 2020 Aug 20;6:49. doi: 10.1186/s40900-020-00228-z. eCollection 2020. PubMed 32843994 ↗
  • Skipper C, Schleiss MR, Bangdiwala AS, Hernandez-Alvarado N, Taseera K, Nabeta HW, Musubire AK, Lofgren SM, Wiesner DL, Rhein J, Rajasingham R, Schutz C, Meintjes G, Muzoora C, Meya DB, Boulware DR. Cytomegalovirus Viremia Associated With Increased Mortality in Cryptococcal Meningitis in Sub-Saharan Africa. Clin Infect Dis. 2020 Jul 27;71(3):525-531. doi: 10.1093/cid/ciz864. PubMed 31504335 ↗
  • Bayiyana A, Okurut S, Nabatanzi R, Zziwa G, Boulware DR, Lutwama F, Meya D. Longitudinal Changes in Cd4+, Cd8+ T Cell Phenotype and Activation Marker Expression Following Antiretroviral Therapy Initiation among Patients with Cryptococcal Meningitis. J Fungi (Basel). 2019 Jul 17;5(3):63. doi: 10.3390/jof5030063. PubMed 31319498 ↗
  • Tugume L, Rhein J, Hullsiek KH, Mpoza E, Kiggundu R, Ssebambulidde K, Schutz C, Taseera K, Williams DA, Abassi M, Muzoora C, Musubire AK, Meintjes G, Meya DB, Boulware DR; COAT and ASTRO-CM teams. HIV-Associated Cryptococcal Meningitis Occurring at Relatively Higher CD4 Counts. J Infect Dis. 2019 Feb 23;219(6):877-883. doi: 10.1093/infdis/jiy602. PubMed 30325463 ↗
09

Registry details

Key details

Study ID
NCT01075152
Lead sponsor
University of Minnesota
Collaborators
Mbarara University of Science and Technology, Makerere University, National Institute of Allergy and Infectious Diseases (NIAID), University of Cape Town
Responsible party
Sponsor
First posted
Feb 24, 2010
Start date
Nov 2010
Primary completion
Oct 2012
Completion
Mar 2013
Results posted
Aug 20, 2014
Last update
Jun 9, 2020

Study contacts

David R Boulware, MD, MPH
principal investigator · University of Minnesota

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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