Acquired Immunodeficiency Syndrome Clinical Trial
Official title:
Comparison of the Development of Thymidine Analogue Mutations With CD4 Monitoring Alone Versus CD4 Monitoring Plus Viral Load Monitoring in Naive HIV-1 Individuals on First-Line Antiretroviral Therapy in Africa
This study will examine whether HIV-infected patients are more likely to develop resistance
to antiretroviral therapy if their blood is not monitored for the number of viruses (viral
load) in the body.
A virus that changes (mutates) over time may become resistant to certain types of medicine.
This resistance may affect future treatment options. This study will compare the amount of
virus in the blood of HIV-infected patients who have been monitored for viral load with the
amount of virus in the blood of patients who have not been monitored for viral load. For
patients who have detectable virus, the type of resistance (mutations) of the virus will be
determined by comparing the components of the virus with that of a virus that is known not to
be resistant.
HIV-infected patients 18 years of age or older who are being treated at the Infectious
Diseases Institute at Mulago Hospital at Makerere University in Kampala, Uganda, may be
eligible for this study. Participants are interviewed about the treatments they have received
for HIV and how they usually take their anti-HIV drugs. They also have a blood sample drawn
for research tests.
Antiretroviral therapy (ART) has become widely available in resource limited settings (RLS)
due to large increases in available resources through the President s Emergency Plan for AIDS
Relief (PEPFAR) and the Global Fund for AIDS, Tuberculosis, and Malaria (GFATM). The number
of people accessing ART in RLS doubled in 2005 alone. Whereas viral load testing is done
routinely for individuals on ART in the western hemisphere, this is not the case elsewhere.
The World Health Organization (WHO) has recommended only clinical and CD4 count monitoring as
the standard of care in RLS during the ART scale-up. As a result, there is a growing
population of individuals in Africa currently on ART whose treatment is monitored only using
clinical evaluations and CD4 counts.
In addition to preserving lives and improving the quality of life of HIV infected
individuals, the goal of ART is to achieve and maintain suppression of HIV replication to an
undetectable level. This goal enables the treatment to remain effective in the long term
since the emergence of resistant strains is limited by the low replication rate of HIV
achieved under these conditions. The recovery of the immune system as determined through CD4
count monitoring is neither a very sensitive nor specific marker of virological suppression
in individuals on ART. Therefore, monitoring the response to ART using just the WHO
guidelines for RLS may lead to a significant delay in detecting the failure to achieve or
maintain virological suppression among individuals who are failing treatment. This is in
contrast to western settings where routine viral load testing leads to early detection of
failure to achieve suppression.
Failure to monitor and detect unsuppressed virus increases the risk of development of
resistance to ART. In particular, failure to achieve or maintain virologic suppression for
prolonged periods of time may lead to the sequential development of thymidine analogue
mutations (TAMs) in patients taking zidovudine (AZT) or stavudine (d4T) as part of ART
regimens. The accumulation of 3 or 4 TAMs confers drug resistance across the nucleoside
reverse transcriptase inhibitors (NRTI) class of antiretroviral (ARV) drugs and has
implications for future ART regimens, particularly in RLS where second line ART options are
limited. Stavudine and zidovudine are currently used as part of the first line regimens in
Sub-Saharan Africa and other RLS areas.
We hypothesize that patients who are monitored with a combination of CD4 counts and viral
load measurements routinely develop TAMs at a slower rate than do patients who are monitored
with only CD4 count measurement (as per WHO guidelines in RLS). This hypothesis is based on
the higher risk of delay in detection of unsuppressed virus in patients who are monitored by
clinical and CD4 counts alone, which may translate into the development of drug-resistant
mutations.
The study team therefore proposes to carry out a cross-sectional study in a large public HIV
out-patient clinic in which patients who are routinely monitored with both CD4 count and
viral load measurements are compared with patients who are routinely monitored with CD4
counts measurement only. Individuals who have detectable viral load after 36 months of ARV
therapy in each of the above patient categories shall undergo a structured interview and HIV
genotypic testing, particularly to look for TAMs. The presence of TAMs in each instance shall
be documented.
The results of this study will highlight the magnitude of the risk of using CD4 count
monitoring only in patients on ART in RLS and contribute to efforts to find cheaper
technologies for virological monitoring of these individuals. The findings will also support
the choice of second line drug regimens that may be proposed for use in Africa.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT01968551 -
Phase 3 Open-Label Study to Evaluate Switching From Optimized Stable Antiretroviral Regimens Containing Darunavir to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) Plus Darunavir (DRV) in Treatment Experienced HIV-1 Positive Adults
|
Phase 3 | |
Completed |
NCT02929069 -
A Unified Intervention for Young Gay and Bisexual Men's Minority Stress, Mental Health, and HIV Risk
|
N/A | |
Recruiting |
NCT02392884 -
HIV Medication Adherence in Underserved Populations
|
N/A | |
Completed |
NCT02264509 -
Peripheral Arterial Insufficiency Associated With HIV/AIDS
|
N/A | |
Completed |
NCT02583464 -
Bioequivalence Study of Two Formulations With the Association of Tenofovir 300 mg and Emtricitabine 200 mg.
|
Phase 1 | |
Completed |
NCT01440569 -
Safety and Efficacy of Cobicistat-boosted Darunavir in HIV Infected Adults
|
Phase 3 | |
Completed |
NCT00551330 -
Vicriviroc in HIV(R5/X4)-Treatment Experienced Subjects (Study P05057AM5)(COMPLETED)
|
Phase 2 | |
Completed |
NCT00381212 -
A Pilot Study to Investigate the Safety and Immunologic Activity AGS-004 an Autologous HIV Immunotherapeutic Agent.
|
Phase 1/Phase 2 | |
Completed |
NCT00097006 -
Retrovirus Epidemiology Donor Study-II (REDS-II)
|
N/A | |
Completed |
NCT00001409 -
Genetically Modified Lymphocytes to Treat HIV-Infected Identical Twins - Study Modifications
|
Phase 1 | |
Completed |
NCT00000590 -
Anti-HIV Immunoglobulin (HIVIG) in Prevention of Maternal-Fetal HIV Transmission (Pediatric ACTG Protocol 185)
|
Phase 3 | |
Completed |
NCT00000587 -
Erythropoietin for Anemia Due to Zidovudine in Human Immunodeficiency Virus Infection
|
Phase 2 | |
Completed |
NCT00005273 -
Pulmonary Complications of HIV Infection Study (PACS)
|
N/A | |
Completed |
NCT00005303 -
Effectiveness of AIDS Antibody Screening
|
N/A | |
Completed |
NCT00005301 -
Transfusion Safety Study (TSS)
|
N/A | |
Completed |
NCT00001650 -
Use of Bromodeoxyuridine to Study White Blood Cell Replication and Survival in HIV-Infected Patients
|
N/A | |
Withdrawn |
NCT00243568 -
Vicriviroc, a CCR5 Inhibitor, Added to an Optimized Antiretroviral Therapy for Previously Treated HIV (VICTOR-E2) (Study P04285
|
Phase 3 | |
Recruiting |
NCT05031819 -
Managing Hypertension Among People Living With HIV
|
N/A | |
Completed |
NCT00394004 -
Decision-Making of Hispanics and African-Americans With HIV/AIDS Participating in Clinical Trials
|
N/A | |
Completed |
NCT01967940 -
Efficacy of Tenofovir Alafenamide Versus Placebo Added to a Failing Regimen Followed by Treatment With Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Atazanavir in HIV-1 Positive, Antiretroviral Treatment-Experienced Adults
|
Phase 3 |