Primary: to investigate the most importants determinants of the viral dynamics of low-level viremia. Secondary: to investigate the effects on immune activation, neurocognitive performance and periodontal status.
ID
Source
Brief title
Condition
- Immunodeficiency syndromes
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Evolution, as measured by genetic variation of viral clones at different time
points. This outcome gives an indication if the low-level viremia is based on
viral replication or production.
Secondary outcome
HIV-RNA-level, Immunological markers, neurocognitive performance, periodontal
inflammation, HIV resistance associated mutations, Genetic compartmentalization
of HIV (CSF-plasma and saliva-plasma comparison).
Background summary
HIV low-level viremia is a frequently observed clinical phenomenon and a
possible risk for the development of drug resistance and virological failure
[1]. The origin of low-level viremia is not known, but it is hypothesized that
virus production or virus replication in cellular and anatomical reservoirs are
involved. The viral activity related with low-level viremia may be associated
with higher levels of immune activation, deterioration of neurocognitive
performance and periodontitis. These are frequently observed problems in the
HIV-infected population. Regarding management of HIV low level viremia,
guidelines differ in their advices. Clinicians usually change the combination
antiretroviral therapy (cART) to a regimen that contains a high genetic barrier
protease inhibitor (PI) to prevent the development of resistance mutations. The
preferred choice is most often darunavir (DRV), boosted with ritonavir
(DRV/r). By systematically studying the effects of starting a high genetic
barrier drug we can safely obtain insights in the dynamics of low-level viremia
and its etiology.
Study objective
Primary: to investigate the most importants determinants of the viral dynamics
of low-level viremia.
Secondary: to investigate the effects on immune activation, neurocognitive
performance and periodontal status.
Study design
An observational cohort-study of 48 weeks with subjects having low-level
viremia that undergo a treatment change containing a high genetic barrier
protease inhibitor.
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: The study will include 6 hospital visits. To a
great extent it includes normal clinical practice regarding clinical history
taking, physical examination, viral load assessment, CD4 count measurements,
lumbar punctures (on indication) and safety controls in blood to monitor
potential side-effects. The additional burden lies in: questionnaires (about
adherence, depression and self-reported impairment in daily functioning),
additional blood samples for virological, immunological and pharmacological
analyses, 3 times a set of validated neurocognitive tests for 40 minutes and
two (optional) periodontitis measurements.
Subjects will be informed about their personal neurocognitive test results
after completion of the study at 48 weeks, unless there is a medical reason for
intervention (e.g. depression). Out of ethical considerations, subjects with
cognitive impairment at the end of the study will be offered a thorough
neurocognitive investigation by a clinical neuropsychologist and offered a
revalidation programme to cope with the impairment if deemed necessary or
useful.
Heidelberglaan 100
Utrecht 3508 GA
NL
Heidelberglaan 100
Utrecht 3508 GA
NL
Listed location countries
Age
Inclusion criteria
a. Using cART for at least 48 weeks, including 2 NRTIs + 1 NNRTI or 1 PI or 1INSTI
b. Low level viremia (2 or more HIV viral loads between 50-1000 cp/mL in a year, without Target Not Detected (TND) in between)
c. Viral load <200cp/mL at at least one measurement since starting cART
d. A planned therapy change of the PI or NNRTI to DRV/r
Exclusion criteria
a. Presence of known pol major IAS mutations for darunavir (I47V; I50V; I54M/L; L76V; I84V)
b. Signs of opportunistic infections
c. Major suspicion of inadequate therapy adherence
d. Severe depression at screening (BDI score >30)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL47035.041.13 |