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The GAIN (Greater Access and Impact with NAT) Study: Improving HIV Diagnosis, Linkage to Care, and Prevention Services with HIV Point-of-Care Nucleic Acid Tests (NATs)

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The GAIN (Greater Access and Impact with NAT) Study: Improving HIV Diagnosis, Linkage to Care, and Prevention Services with HIV Point-of-Care Nucleic Acid Tests (NATs)



NEW




SUPPORTING STATEMENT B






June 9, 2021





Project Officers

Mary Tanner, MD

Phone: 404-639-6376

Fax: 404-639-6127

Email: [email protected]


Kirk D. Henny, PhD

Phone: 404-639-5383

Fax: 404-639-6127

Email: [email protected]



Centers of Disease Control and Prevention

National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention

Division of HIV/ AIDS Prevention- Surveillance and Epidemiology
HIV Epidemiology Branch

1600 Clifton Rd., MS E-45

Atlanta, GA 30333


TABLE OF CONTENTS


B. Statistical Methods


  1. Respondent Universe.

  2. Procedures for the Collection of Information

  3. Methods to Maximize Response Rates and Deal with Nonresponse

  4. Tests of Procedures or Methods to be Undertaken.

  5. Individuals Consulted on Statistical Aspects and Individuals Collecting and/or Analyzing Data.



EXHIBITS


Exhibit 1. Planned Maximum and Estimated Annual Study

Enrollment, by Study Activity Groups

Exhibit 2. Sample Size Table for Evaluation of Effect of POC NAT on

PrEP Initiation

Exhibit 3. Sample Size Table for Evaluation of Impact of POC NAT on

Time to Virologic Suppression

Exhibit 4. Study Aims, Key Data Elements, and Planned Analyses

Exhibit 5. CDC GAIN staff involved in analyses



LIST OF ATTACHMENTS

Att. 1 Authorizing Legislation

Att. 2 60-Day Federal Register Notice

Att. 2A Public comments in response to 60-Day FRN

Att. 3 GAIN study activities and visual overview

Att. 4 GAIN data sources and variables table

Att. 5 GAIN monthly study report form

Att. 6 GAIN IRB approval letter

Att. 7 Privacy Impact Assessment (PIA)

Att. 8 Consent form: GAIN Study – Testing, PEP & PrEP Group

Att. 9 Consent form: GAIN Study – Gay City HIV+ Group

Att. 10 Consent form: GAIN Study – RCT Group

Att. 11 GAIN study visit survey screenshots

Att. 12 POC NAT acceptability survey screenshots

Att. 13 Provider focus group and interview guides

Att. 14 GAIN ROI form

Att. 15 Baseline data collection variables list

Att. 16 GAIN patient information sheet




B. Statistical Methods


1. Respondent Universe.

The GAIN (Greater Access and Impact with NAT) Study will take place at two clinical sites: Madison Clinic and Gay City Clinic. Attachment 3, GAIN study activities and visual overview, illustrates the relationships between study aims and activities.

Persons seeking medical care at the clinic sites will be approached for study participation if they meet inclusion criteria. Only persons ≥18 years of age or older who can speak and read in English will be offered study participation. For the prospective study of HIV-negative patients, criteria include persons seeking HIV testing, PrEP, or PEP services. For the prospective study of HIV-positive patients, criteria include persons seeking sexually transmitted infection (STI) testing. For the RCT, criteria include HIV-positive persons seeking care at Gay City Clinic. The study will aim to recruit participants who are more likely to have detectable HIV RNA based on prior viral load test results, adherence and visit history, and whose providers are willing to work with the study to deliver a brief adherence intervention based on the POC NAT result. For the patient survey/interview/focus group, criteria include HIV-positive and HIV-negative persons who received a POC NAT test as part of participation in one of the other study activities. For the cross-sectional comparison of POC NATS, criteria include persons who are HIV-positive and seeking care at Madison Clinic. The study will aim for about half of the participants recruited to this group to have detectable HIV RNA based on prior viral load test results. For the acceptability/feasibility assessment among providers group, criteria include being a provider in Madison or Gay City clinics.

Exhibit 1. Planned Maximum and Estimated Annual Study Enrollment, by Study Activity Groups

Study Activity Group

Maximum Enrollment

Estimated Annual Enrollment

Prospective study of HIV-negative patients seeking HIV testing, PrEP, or PEP services


4600

1530

Prospective study of HIV-positive patients seeking STI testing


500

165

RCT of POC NAT or Standard of Care for HIV-positive patients


1000

333

Survey group examining POC NAT acceptability among HIV-negative and HIV-positive patients


350

117

Cross-sectional comparison of several point-of-care NATs among HIV-positive patients


1000

333

Acceptability/feasibility assessment among clinical and community providers


100

33


Review of clinical baseline data indicates that study enrollment targets can be achieved. From 2016-2018, there were 13,313 visits to Gay City by HIV-negative patients seeking testing or PrEP, 76 new HIV-positive diagnoses, and 367 visits by HIV-positive patients for STI testing. At Madison Clinic in 2017-2018, there were 26,931 visits by 5,527 HIV-positive patients, with 521 of those testing with a viral load of >40. In addition, there were 541 PEP patients and 284 PrEP patients seen..

Statistical planning included sample size calculations which indicate that the enrollment plan is appropriate for study aims. There are unknown variables (e.g. PrEP uptake) that affect sample size considerations. The study team will monitor, evaluate, and discuss study enrollment, sample size considerations, and prioritization of the various study aims throughout the enrollment period.


Exhibit 2. Sample Size Table for Evaluation of Effect of POC NAT on PrEP Initiation


0.5% PrEP uptake

1.0% PrEP uptake

2.0% PrEP uptake

3.0% PrEP uptake

4.0% PrEP uptake

1:1, baseline 2%

13809 / 13809

3826 / 3826

1141 / 1141

588 / 588

376 / 376

1:2, baseline 2%

10504 / 21007

2941 / 5881

891 / 1781

464 / 927

298 / 596

1:4, baseline 2%

8847 / 35387

2495 / 9980

762 / 3048

399 / 1594

257 / 1028

1:1, baseline 4%

25551 / 25551

6745 / 6745

1863 / 1863

906 / 906

553 / 553

1:2, baseline 4%

19305 / 38610

5129 / 10257

1432 / 2863

701 / 1402

431 / 861

1:4, baseline 4%

16180 / 64720

4319 / 17274

1214 / 4854

598 / 2389

368 / 1471

1:1, baseline 6%

36791 / 36791

9540 / 9540

2554 / 2554

1209 / 1209

721 / 721

1:2, baseline 6%

27729 / 55458

7222 / 14443

1948 / 3896

928 / 1856

557 / 1113

1:4, baseline 6%

23197 / 92787

6062 / 24245

1644 / 6576

787 / 3145

473 / 1892

alpha = 0.05, power = 80%


Exhibit 3. Sample Size Table for Evaluation of Impact of POC NAT on Time to Virologic Suppression

Standard of Care

10% increase

20% increase

30% increase


n per arm

HR

n per arm

HR

n per arm

HR

10%

202

0.47

65

0.30

35

0.21

20%

295

0.63

84

0.44

41

0.32

30%

354

0.70

94

0.52

44

0.39

40%

379

0.74

96

0.56

43

0.42

         

Assuming 20% loss to follow-up

10%

225

0.47

72

0.30

39

0.21

20%

327

0.63

93

0.44

46

0.32

30%

392

0.70

104

0.52

48

0.39

40%

418

0.74

106

0.56

47

0.42


2. Procedures for the Collection of Information

Retrospective baseline data collection from clinical site electronic medical records will establish baseline PrEP and HIV care metrics for comparison after study implementation. UW has identified and will use clinical databases (e.g. INSYNC database, UWHIS database) to extract necessary study data without the need for additional collection (Attachment 4. GAIN data sources and variables table). Study procedures for other study activities are as outlined in Attachment 3. GAIN study activities and visual overview.


Exhibit 4. Study Aims, Key Data Elements, and Planned Analyses

Aim

Aim Description

Key Data Elements

Planned Analyses

1

Evaluate impact of POC NAT on PrEP-related clinical outcomes

  • Number of HIV-negative persons tested

  • Number of persons tested at PrEP start

  • Demographics

  • Number of persons initiating PrEP

  • Time from 1st PrEP visit to PrEP start

  • Number of persons tested on PrEP

  • Duration PrEP persistence

  • Compare proportions of participants in the pre-and post-implementation phases who initiate PrEP within 1 month of HIV testing at Gay City, controlling for risk score.

  • Compare time from initial PrEP visit to PrEP start in the pre- and post-implementation phases.

  • Evaluate impact of race/ethnicity and other factors on proportions initiating PrEP within 1 month of testing.

  • Evaluate impact of POC NAT on PrEP initiation within 1 month of testing, using contemporaneous controls.

  • Describe feasibility of same-day PrEP starts using an immediate access telemedicine provider.

  • Compare PrEP persistence at 6 and 12 months, using POC NAT as a time-varying covariate.

2

Evaluate impact of POC NAT on HIV care continuum outcomes

  • Number of persons newly dx w/ HIV

  • Sensitivity and specificity c/w pooled NAT

  • Care continuum (linkage, ART, VL)

  • Estimate sensitivity and specificity of POC NAT among persons testing for HIV at both sites.

  • Compare proportions of persons initiating ART within 30 days in the pre- and post-implementation phases.

  • Describe impact of POC NAT on time to linkage to HIV care, ART initiation, and virologic suppression.

3

Evaluate impact of POC NAT on time to virologic suppression

  • Number of people living with HIV tested by POC NAT

  • Sensitivity and specificity c/w plasma RNA

  • Linkage/re-linkage to care

  • Number of people living with HIV enrolled in RCT

  • Time to suppression, POC NAT versus standard of care

  • Develop and refine a brief POC NAT-tailored behavioral intervention to be used by HIV care providers

  • Recruit participants with low adherence or detectable viremia and compare time to virologic suppression among participants randomized to the POC NAT-tailored intervention or to standard of care.

  • Describe uptake of POC NAT testing among HIV-positive persons seeking STI testing at a community site.

  • Compare ability of POC and laboratory-based NAT to identify persons with virologic failure.

  • Compare proportions of HIV-positive testers at Gay City in the pre- and post-implementation phases who report being undetectable 6 months after the testing visit.

4

To quantify acceptability and feasibility of POC NAT and collect cost and related data

  • Percentage of persons tested receiving results

  • Acceptability among persons tested

  • Acceptability/feasibility among staff

  • Cost data

  • Develop models for use of POC NAT in community and clinical settings.

  • Quantify the proportions of participants who receive POC NAT results during visits.

  • Assess acceptability and feasibility of POC NAT implementation in community and clinical settings.

  • To quantify cost-effectiveness of POC NAT implementation.

5

To compare sensitivity and specificity of multiple POC NATs over a range of HIV RNA levels

  • Sensitivity and specificity multiple POC NAT

  • Calculate the agreement between multiple POC NATs, using a threshold of 1000 HIV copies/mL.

  • Compare sensitivity and specificity of POC NATs, using a reference laboratory-based NAT as gold standard.


3. Methods to Maximize Response Rates and Deal with Nonresponse

Persons who enroll in the study at each Gay City and at Madison Clinic (in the prospective or RCT study activities) will be offered participation in an online survey (to be completed later in a private setting of their choosing) during their study visit. The survey link will be sent to them within a few business days via email. The survey duration is estimated at 20 minutes. Participants will have 7 days to complete the survey before the link expires. Participants will receive a $10 gift card upon completion of the survey. To promote survey response, participants will be sent up to two automated reminders after the initial email to complete the survey.

It is anticipated that this survey will have a >80% response rate. This high rate of response is anticipated because participants will be approached about survey group inclusion during in-person medical visits, and only persons who agree to participate will be sent the survey. Additionally, the modest survey duration and use of reminders are expected to reduce barriers to survey completion.


4. Tests of Procedures or Methods to be Undertaken.

No pilot tests of data collection instruments are anticipated.


5. Individuals Consulted on Statistical Aspects and Individuals Collecting and/or Analyzing Data.

The statistician for the GAIN project at CDC is Jeff Wiener ([email protected]; 770-488-6106) of the Statistical Science Team in the Quantitative Sciences and Data Management Branch of the Division of HIV/AIDS Prevention.

De-identified GAIN study data received at CDC from UW will be analyzed by CDC GAIN study staff, detailed in the table below.


Exhibit 5. CDC GAIN staff involved in analyses

CDC Investigator

Phone

Email

Kirk Henny

404.639.5383

[email protected]

Mary Tanner

404.639.6376

[email protected]

Karen Hoover

404.639.8534

[email protected]

Kevin Delaney

404.639.8630

[email protected]

Joshua Betts

404.639.5321

[email protected]

Kashif Iqbal

404.718.8556

[email protected]

Damian Denson

404.639.6125

[email protected]

Cari Courtenay-Quirk

404.639.1924

[email protected]

Jeffrey Wiener

770.488.6106

[email protected]

Jeffrey Johnson

404.639.4976

[email protected]

Amanda Smith

404.639.2978

[email protected]

Tanja Walker

404.718.8569

[email protected]



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