Trial Outcomes & Findings for Resistance Testing to Improve Management of Virologic Failure in Sub-Saharan Africa (NCT NCT02787499)
NCT ID: NCT02787499
Last Updated: 2023-03-21
Results Overview
Number and percentage of participants achieving virologic suppression. Virologic resuppression defined as viral load \< 200 copies/mL
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
840 participants
Primary outcome timeframe
9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
Results posted on
2023-03-21
Participant Flow
Participant milestones
| Measure |
Standard of Care
Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load \<1,000 copies/mL at repeat testing will be retained on first-line therapy.
|
HIV-1 RNA Resistance Testing
Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing.
HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
|
|---|---|---|
|
Overall Study
STARTED
|
423
|
417
|
|
Overall Study
COMPLETED
|
423
|
417
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Resistance Testing to Improve Management of Virologic Failure in Sub-Saharan Africa
Baseline characteristics by cohort
| Measure |
Standard of Care
n=423 Participants
Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load \<1,000 copies/mL at repeat testing will be retained on first-line therapy.
|
HIV-1 RNA Resistance Testing
n=417 Participants
Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing.
HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
|
Total
n=840 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
415 Participants
n=5 Participants
|
412 Participants
n=7 Participants
|
827 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Age, Continuous
|
37 years
n=5 Participants
|
37 years
n=7 Participants
|
37 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
221 Participants
n=5 Participants
|
209 Participants
n=7 Participants
|
430 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
202 Participants
n=5 Participants
|
208 Participants
n=7 Participants
|
410 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
423 Participants
n=5 Participants
|
417 Participants
n=7 Participants
|
840 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Uganda
|
210 participants
n=5 Participants
|
210 participants
n=7 Participants
|
420 participants
n=5 Participants
|
|
Region of Enrollment
South Africa
|
213 participants
n=5 Participants
|
207 participants
n=7 Participants
|
420 participants
n=5 Participants
|
|
Median Antiretroviral therapy (ART) duration
|
3.5 years
n=5 Participants
|
3.0 years
n=7 Participants
|
3.2 years
n=5 Participants
|
|
Country
Uganda
|
210 Participants
n=5 Participants
|
210 Participants
n=7 Participants
|
420 Participants
n=5 Participants
|
|
Country
South Africa
|
213 Participants
n=5 Participants
|
207 Participants
n=7 Participants
|
420 Participants
n=5 Participants
|
|
Pregnancy
Pregnant at enrollment
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Pregnancy
Not pregnant at enrollment
|
416 Participants
n=5 Participants
|
411 Participants
n=7 Participants
|
827 Participants
n=5 Participants
|
|
Median CD4 count
|
0.303 x 10^9 cells/L
n=5 Participants
|
0.259 x 10^9 cells/L
n=7 Participants
|
0.281 x 10^9 cells/L
n=5 Participants
|
|
ART regimen
TDF-3(F)TC-EFV
|
311 Participants
n=5 Participants
|
295 Participants
n=7 Participants
|
606 Participants
n=5 Participants
|
|
ART regimen
AZT-3TC-NVP
|
60 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
118 Participants
n=5 Participants
|
|
ART regimen
Other
|
52 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
116 Participants
n=5 Participants
|
|
Self-reported treatment adherence at enrollment
<100% in prior 30 d
|
297 Participants
n=5 Participants
|
295 Participants
n=7 Participants
|
592 Participants
n=5 Participants
|
|
Self-reported treatment adherence at enrollment
100% in prior 30 d
|
126 Participants
n=5 Participants
|
122 Participants
n=7 Participants
|
248 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)Number and percentage of participants achieving virologic suppression. Virologic resuppression defined as viral load \< 200 copies/mL
Outcome measures
| Measure |
Standard of Care
n=423 Participants
Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load \<1,000 copies/mL at repeat testing will be retained on first-line therapy.
|
HIV-1 RNA Resistance Testing
n=417 Participants
Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing.
HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
|
|---|---|---|
|
Number and Percentage of Patients Achieving Virologic Resuppression
|
256 Participants
|
263 Participants
|
SECONDARY outcome
Timeframe: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)Number and percentage of patients with an undetectable viral load (below limit of detection) at study conclusion. Viral load \< 200 copies/mL
Outcome measures
| Measure |
Standard of Care
n=423 Participants
Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load \<1,000 copies/mL at repeat testing will be retained on first-line therapy.
|
HIV-1 RNA Resistance Testing
n=417 Participants
Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing.
HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
|
|---|---|---|
|
Number and Percentage of Patients With an Undetectable Viral Load (Below Limit of Detection) at Study Conclusion
|
193 Participants
|
202 Participants
|
SECONDARY outcome
Timeframe: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)The number and percentage of patients with an undetectable viral load on first-line (NNRTI-based) therapy at study conclusion. Viral load \< 200 copies/mL
Outcome measures
| Measure |
Standard of Care
n=423 Participants
Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load \<1,000 copies/mL at repeat testing will be retained on first-line therapy.
|
HIV-1 RNA Resistance Testing
n=417 Participants
Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing.
HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
|
|---|---|---|
|
Number and Percentage of Patients With an Undetectable Viral Load on First-line (NNRTI-based) Therapy at Study Conclusion
|
81 Participants
|
62 Participants
|
SECONDARY outcome
Timeframe: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)Proportion of patients with International AIDS Society-defined drug resistance mutations to their current regimen. As part of this analysis, we will also evaluate for minority drug resistance
Outcome measures
| Measure |
Standard of Care
n=103 Participants
Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load \<1,000 copies/mL at repeat testing will be retained on first-line therapy.
|
HIV-1 RNA Resistance Testing
n=82 Participants
Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing.
HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
|
|---|---|---|
|
Number and Percentage of Patients With International AIDS Society-defined Drug Resistance Mutations to Their Current Regimen.
|
25 Participants
|
34 Participants
|
SECONDARY outcome
Timeframe: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)Total patient care costs, including diagnostic testing and ART costs for the study duration. These data are reported as median cost and IQR per person by arm.
Outcome measures
| Measure |
Standard of Care
n=423 Participants
Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load \<1,000 copies/mL at repeat testing will be retained on first-line therapy.
|
HIV-1 RNA Resistance Testing
n=417 Participants
Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing.
HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
|
|---|---|---|
|
Total Patient Care Costs, Including Diagnostic Testing and ART Costs for the Study Duration
|
227 dollars
Interval 124.0 to 416.0
|
400 dollars
Interval 304.0 to 579.0
|
SECONDARY outcome
Timeframe: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)The number and percentage of patients retained in HIV clinical care at study completion
Outcome measures
| Measure |
Standard of Care
n=423 Participants
Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load \<1,000 copies/mL at repeat testing will be retained on first-line therapy.
|
HIV-1 RNA Resistance Testing
n=417 Participants
Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing.
HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
|
|---|---|---|
|
Number and Percentage of Patients Retained in HIV Clinical Care at Study Completion
|
403 Participants
|
394 Participants
|
SECONDARY outcome
Timeframe: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)Odds of 9-month survival. Number and percentage of participants who survived through the 9-month (then 15-month) study period.
Outcome measures
| Measure |
Standard of Care
n=423 Participants
Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load \<1,000 copies/mL at repeat testing will be retained on first-line therapy.
|
HIV-1 RNA Resistance Testing
n=417 Participants
Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing.
HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
|
|---|---|---|
|
Number and Percentage of Participants Survived Through 9-month Study Period
|
415 Participants
|
403 Participants
|
SECONDARY outcome
Timeframe: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)Population: This analysis was completed for participants with complete utility data at visit 3 (at 9 months or 15 months due to the pandemic). There was missing HRQoL data for 24 participants in the Standard of Care arm and 19 participants in the Resistance Testing arm at visit 3. Therefore, the numbers of participants for this outcome are different from other outcome measures.
Change in health-related quality of life from baseline to 9 months. The scale used is Health-related Quality of Life (HRQoL), where the minimum score is 0 = 'death' and the maximum is 1 = 'perfect' health. We are reporting mean change in HRQoL, so a larger positive value indicates a larger improvement of HRQoL. Two time points used in the calculation were the HRQoL score at the baseline visit and at the final visit at 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic).
Outcome measures
| Measure |
Standard of Care
n=399 Participants
Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load \<1,000 copies/mL at repeat testing will be retained on first-line therapy.
|
HIV-1 RNA Resistance Testing
n=398 Participants
Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing.
HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
|
|---|---|---|
|
Change in Health-related Quality of Life From Baseline to 9 Months
|
0.064 score on a scale
Interval 0.042 to 0.086
|
0.078 score on a scale
Interval 0.053 to 0.102
|
Adverse Events
Standard of Care
Serious events: 0 serious events
Other events: 0 other events
Deaths: 8 deaths
HIV-1 RNA Resistance Testing
Serious events: 0 serious events
Other events: 0 other events
Deaths: 14 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Mark Siedner
Massachusetts General Hospital/Harvard Medical School
Phone: 6177264686
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place