Clinical trial NCT00929604: HIV Viral Load Monitoring in Resource-Poor Settings
Official title: Effectiveness of HIV Viral Load Monitoring of Patient Outcome in Resource-Poor Settings
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV
AIDS
HIV Infections
Keywords: HIV
AIDS
Zambia
viral load
antiretroviral therapy
cluster randomization
ART monitoring
treatment failure
randomized clinical trial
treatment naive
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: Adult AIDS Clinical Trials Group
First posted: 2009-06-29
Enrollment: 2112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: No randomized clinical trial to date has demonstrated a survival benefit of using regular HIV-1 ribonucleic acid (RNA) viral load (VL) testing to monitor patients' responses to antiretroviral therapy (ART) for HIV infection. The measurement of VL is recommended to monitor the response to ART in developed countries. In resource-constrained settings, the World Health Organization (WHO) does not recommend routine VL testing, in part due to the cost and complex infrastructure needed for reliable results. In these settings, WHO has proposed the use of clinical and CD4+ lymphocyte-based criteria to guide treatment decisions. However, multiple studies have demonstrated the poor performance of these criteria in sub-Saharan Africa and the frequent discordance between immunologic and virologic responses to ART.

The use of routine viral load monitoring should be evaluated in resource-constrained settings. The investigators hypothesize that routine viral load testing of patients on ART will improve patient survival, decrease disease progression and development of drug resistance, and will be feasible and cost-effective for resource-constrained settings.

Detailed description: The study 'Effectiveness of HIV Viral Load Monitoring on Patient Outcome in Resource-Poor Settings,' is a dual-arm, cluster randomized trial to evaluate the use of routine plasma HIV-1 VL monitoring to improve survival and decrease HIV disease progression in patients receiving ART. The primary objective is to assess mortality at 36 months among ART naïve patients initiating therapy and receiving care at facilities with access to routine HIV VL testing (at ART initiation, at 3 months and at every 6 months thereafter) compared to those initiating first regimens and receiving care at facilities according to our local standard of care (which uses immunological \[i.e. CD4+ lymphocyte count-based\]and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree).

Eligibility criteria: Inclusion Criteria:

* Documented HIV-1 infection (according to local standard rapid testing algorithms)
* Age 18 years or greater
* Able and willing to provide informed consent to participate
* Eligible for antiretroviral therapy per Zambian national guidelines, which are any of the following:

  * CD4+ cell count less than 200 cells/mm3;
  * WHO Stage IV disease; or
  * WHO Stage III disease and CD4+ cell count less than 350 cells/mm3
* Residence in the geographical catchment area of the VLS clinic and intent to remain there for the duration of the study
* Willingness to adhere to the study visit schedule and to be followed-up at home in the event of a missed study visit
* Initiating ART on the day of VLS enrollment, informed consent, and baseline blood collection

Exclusion Criteria:

* Receipt of more than 7 days (cumulative) of prior antiretroviral therapy at any time prior to study entry, with the exception of zidovudine and/or single dose nevirapine for prevention of mother-to-child transmission;
* Any exposure to antiretroviral therapy in the past one month
* A condition that, in the opinion of the investigators, would interfere with adherence to study requirements (e.g., mental illness or active drug or alcohol use or dependence)
* Serious illness requiring referral to hospital at the time of ART initiation
* For patients seeking care at sites randomized to the standard of care arm: participation in another research protocol that offers routine viral load testing
* Unwillingness to consent to all aspects of study protocol including blood specimen storage

Primary outcomes:
measure: Patient survival
timeFrame: 36 months
Secondary outcomes:
measure: To assess HIV clinical disease progression (weight, CD4 cell response, incident opportunistic infections)
timeFrame: 36 months
measure: To assess the impact of more rapid ART regimen switching on available second and third-line treatment options
timeFrame: 36 months
measure: To monitor the effectiveness of newer antiretroviral medications introduced in Zambia (principally tenofovir)
timeFrame: 36 months
measure: To characterize the timing and sequence of HIV drug resistance development among patients in each study arm
timeFrame: 36 months
measure: To assess the feasibility, acceptability, and cost effectiveness of the two management strategies in a resource-constrained sub-Saharan African setting
timeFrame: 36 months
Other outcomes:
Locations:
city: Lusaka
country: Zambia
facility: Centre for Infectious Disease Research in Zambia
Study officials:
affiliation: University of Alabama at Birmingham
name: Michael S. Saag, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koethe JR, Westfall AO, Luhanga DK, Clark GM, Goldman JD, Mulenga PL, Cantrell RA, Chi BH, Zulu I, Saag MS, Stringer JS. A cluster randomized trial of routine HIV-1 viral load monitoring in Zambia: study design, implementation, and baseline cohort characteristics. PLoS One. 2010 Mar 12;5(3):e9680. doi: 10.1371/journal.pone.0009680.