Viewing Study NCT02614950



Ignite Creation Date: 2024-05-06 @ 7:50 AM
Last Modification Date: 2024-10-26 @ 11:53 AM
Study NCT ID: NCT02614950
Status: COMPLETED
Last Update Posted: 2017-01-27
First Post: 2015-11-23

Brief Title: Viral Suppression After Analytic Treatment Interruption in Thai Patients Who Initiated Highly Active Antiretroviral Therapy During Acute HIV Infection
Sponsor: SEARCH Research Foundation
Organization: SEARCH Research Foundation

Study Overview

Official Title: Viral Suppression After Analytic Treatment Interruption in Thai Patients Who Initiated Highly Active Antiretroviral Therapy During Acute HIV Infection
Status: COMPLETED
Status Verified Date: 2017-01
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: None
Brief Summary: This is a Phase 2 two-step open-label study of the outcome of analytic treatment interruption ATI on patients who started antiretroviral therapy ART during Fiebig Stage I of acute HIV infection AHI defined as detectable HIV-RNA without detectable p24 antigen or HIV IgM The primary endpoint will be rate of sustained viral suppression defined as HIV-1 RNA 50 cpsml at 24 weeks after treatment interruption During ATI subjects will be monitored closely for safety and will have ART re-initiated if they meet predefined clinical virological or immunological criteria In step I there will be 8 subjects who undergo ATI An interim analysis for safety will be conducted after 12 weeks If none of the subjects maintain viral suppression at 12 weeks then no further subjects will be enrolled into the study If at least 1 out of 8 subjects maintains viral suppression at 12 weeks then an additional 7 subjects will be enrolled in step 2

At ATI all antiretroviral drugs will be discontinued Subjects will be monitored with clinical exam immunological CD4 and virological HIV-RNA testing at baseline and then on a fixed schedule for 24 weeks ART will be re-initiated immediately if subjects meet any pre-defined clinical immunological or virological safety endpoints during the monitoring period
Detailed Description: This is a two step open label study of ATI in patients who initiated ART in the earliest detectable stage Fiebig I of HIV infection In step I eight subjects will discontinue ART for a period of up to 24 weeks An interim assessment will be conducted after all eight

subjects in step I complete follow-up for 12 weeks If at least one out of eight subjects maintains viral suppression HIV-1 RNA 50 copiesml at 12 weeks then the study will proceed to step 2 in which 7 additional subjects maximum total sample size of 15 will undergo ATI The primary endpoint is proportion of subjects who maintain viral suppression at 24 weeks post ATI Subjects will be monitored frequently for disease progression using clinical immunological and virological criteria ART will be re-initiated immediately for any subjects who meet pre-defined criteria for disease progression

Parent Study Cohort

This is a sub-study of the protocol Establish and characterize an acute HIV infection cohort in a high-risk population SEARCH 010 RV254 WRAIR 1494 implemented at the Thai Red Cross AIDS Research Center in Bangkok Thailand From April 2009 through February 2014 the cohort had enrolled 150 patients with acute infection and 145 97 are still in active follow-up All patients in the cohort are offered ART at the time of enrollment through a separately funded protocol all 145 subjects 100 in active follow-up are currently on ART The median age range of the cohort is 28 18-57 years and 90 are men who have sex with men MSM

The cohort currently has 50 volunteers who started ART during Fiebig Stage 1 of whom 24 have been on ART for 24 months and have HIV-1 50 copiesml Another 13 volunteers have been on ART 6-24 months with undetectable HIV-1 RNA

During the period of co-enrollment in this substudy no additional biological specimens will be collected as part of the RV254SEARCH 010 protocol Data and samples from this substudy will be shared with the parent protocol

Criteria to reinitiate ART after ATI

The criteria to restart ART after ATI are designed to protect the subjects from any possible clinical immunological or virological adverse effects in the event that their VL rebounds while off ART The viral load VL criterion of 1000 copiesml was chosen because clinical symptoms of HIV infection or significant decline in CD4 count would not be expected at this low level of viremia The Fiebig I patients in the SEARCH 010 cohort had a median range HIV-1 RNA of 48 28-57 log10copiesml at a median range of 12 4-40 days after exposure to HIV prior to initiation ART and have therefore already been exposed to high levels of plasma virus during acute infection while maintaining low or no detectable HIV proviral reservoirs

In addition the ANRS Visconti study found that patients who are virologic controllers sustained VL 50 copiesml after ATI may initially and transiently have VL above detection Of 240 tests performed after treatment interruption in those who were subsequently virologic controllers or PTC 2 had VL 400 copiesml and 18 had VL between 50 and 400 copiesml Therefore low-level viremia may not always be indicative of viral rebound and can potentially reverse

Specific criteria for re-initiation of ART after ATI are

1 HIV-1 RNA above 1000 copiesml on 2 consecutive determinations at least 3 days apart OR
2 HIV-1 RNA rise of 05 log10copiesml per day provided that the last HIV-1 RNA is above 1000 copiesml OR
3 A single HIV-1 RNA above 10000 copiesml OR
4 CD4 T-cell counts below 350 cellsmm3 on 2 consecutive determinations at least 2 weeks apart OR
5 CD4 T-cell count decline of 50 from baseline prior to ATI OR
6 Clinical progression to CDC Category B or C disease OR
7 Diagnosis of Acute Retroviral Syndrome OR
8 Pregnancy OR
9 Subject requests re-initiation of ART

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: None
Is a FDA Regulated Device?: None
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None