HIV Infection
Conditions
Keywords
HIV Infection, HAART, Maternal Health
Brief summary
This study was a randomized strategy trial conducted among women who received highly active antiretroviral therapy (HAART) during pregnancy for purposes of prevention of mother-to-child transmission (PMTCT) of HIV but did not otherwise meet criteria to initiate HAART for their own health. The study was designed to determine whether continuation of HAART after delivery or other pregnancy outcome reduced morbidity and mortality compared to discontinuation and re-initiation of HAART when protocol specified criteria were met.
Detailed description
This randomized strategy trial addressed therapeutic questions for women from regions where antepartum HAART for PMTCT (for all CD4+ cell counts) and postpartum formula feeding is standard of care, and who also had both a pre-HAART CD4+ cell count \>400 cells/mm\^3 and a screening (on-HAART) CD4+ cell count \> 400 cells/mm\^3. For these women, the objectives related to the relative efficacy and safety of continuing HAART (when it is no longer used for PMTCT) versus discontinuing HAART. Potential participants were identified/recruited and consented during pregnancy or after delivery or other pregnancy outcome. Study-specific screening was initiated in the third trimester or after pregnancy outcome. Women who were screened for the study were counseled to continue their HAART until they were randomized. Randomization would occur within 0-42 days after pregnancy outcome. Women who did not carry their pregnancy to the third trimester but otherwise meet study eligibility criteria could be enrolled. Participants were randomized to one of the two study arms: Arm A: Continuation of HAART Arm B: Discontinuation of HAART and resume HAART when protocol-specified criteria were met Participants were to be followed until 84 weeks after the last participant was randomized. Key evaluations were conducted at Screening, Entry, post entry visits were scheduled to take place 4 weeks after entry, 12 weeks after entry, and every 12 weeks thereafter. Key evaluations included physical examinations, clinical assessments, and blood collection. On 7 July 2015, the study sites received formal communications regarding the results of the Strategic Timing of Antiretroviral Treatment (START) study and associated changes were implemented to the 1077HS study in response to these results. All sites were instructed that all women in the 1077HS study were to be informed of the START study results and that antiretroviral therapy (ART) was recommended for all women based on the START study results.
Interventions
A combination of three or more HIV medications belonging to two or more drug classes. The preferred study-supplied HAART regimen was lopinavir/ritonavir (LPV/RTV) plus fixed dose combination tenofovir/emtricitabine (TDF/FTC). Additional ARVs provided for use in this study included fixed dose combination lamivudine/zidovudine (3TC/ZDV), lamivudine (3TC), zidovudine (ZDV), tenofovir (TDF), fixed dose combination tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV), didanosine (ddI), atazanavir (ATV), raltegravir (RAL), and ritonavir (RTV). While LPV/RTV plus TDF/FTC was the preferred study-supplied regimen, the study clinicians in conjunction with participants would determine the optimal drug combination for each participant.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women age ≥ 18 years or who had attained the minimum age of independent consent, as defined by the local Institutional Review Board (IRB), and were willing and able to provide written informed consent Additionally, at sites with IRB approval to enroll younger participants, women age 16-17 years who were willing and able to provide written assent and whose parent or legal guardian was willing and able to provide written informed consent * Confirmed HIV infection, documented by positive results from two samples collected at different time points prior to study entry, using protocol-specified tests (see protocol for more details) * Documentation of hepatitis B surface antibody (HBsAb) status and hepatitis B surface antigen (HBsAg) status (if antibody was negative) within 12 months prior to study entry * Within 0-42 days after pregnancy outcome * Antiretroviral treatment naïve, defined as \< 14 days of one or more antiretroviral agents, prior to therapy initiated during current pregnancy * Receipt of at least four weeks of HAART prior to study entry, at least two weeks of which must have been prior to pregnancy outcome (up to seven consecutive days of missed therapy is permitted) * CD4+ cell count ≥ 400 cells/mm\^3 on a specimen obtained within 120 days prior to initiation of HAART for current pregnancy * CD4+ cell count ≥ 400 cells/mm\^3 on a specimen obtained on HAART and within 45 days prior to study entry * The following laboratory values on a specimen obtained within 45 days prior to study entry: * Absolute neutrophil count ≥ 750/mm\^3 * Hemoglobin ≥ 7.0 g/dL * Platelet count ≥ 50,000/mm\^3 * AST (SGOT), ALT (SGPT), and alkaline phosphatase ≤ 2.5 x ULN * Estimated creatinine clearance of ≥ 60mL/min within 45 days prior to entry using the Cockcroft-Gault formula * Intent to remain in current geographical area of residence for the duration of the study * Willingness to attend study visits as required by the study
Exclusion criteria
* Previous participation in PROMISE (P1077BF - NCT01061151) * Clinical indication for HAART including any World Health Organization (WHO) Clinical Stage 3 or 4 condition, prior or current tuberculosis disease (a positive (Purified protein Derivative) PPD test alone was not considered exclusionary), and/or any other clinical indication per country-specific treatment guidelines * Clinically significant illness or condition requiring systemic treatment and/or hospitalization within 30 days prior to study entry * Social or other circumstances which, in the opinion of the site investigator, would hinder long-term follow up * Use of any prohibited medications within 14 days prior to study entry (refer to the study MOP for a list of prohibited medications) * Current compulsory detention (involuntary incarceration) in a correctional facility, prison, or jail for legal reasons or compulsory detention in a medical facility for treatment of either a psychiatric or physical (e.g., infectious disease) illness * Currently breastfeeding or planning to breastfeed * Current documented conduction heart defect (specialized assessments to rule out this condition were not required; a heart murmur alone and/or type 1 second-degree atrioventricular block (also known as Mobitz I or Wenckebach) was not considered exclusionary) * Known evidence of HBV DNA levels \>2000 IU/mL (approximately 10,000 copies/mL) in the presence of elevated (grade 1 and higher) ALT (HBV DNA testing was not required for study screening or enrollment but was considered to determine whether treatment for HBV was indicated)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rates of AIDS - Defining Illness, Serious Non-AIDS Defining, Cardiovascular, Renal, Hepatic Event, or Death | From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). | AIDS defining illness, serious non-AIDS defining cardiovascular, renal, or hepatic event, or death refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of AIDS - Defining Illness | From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). | AIDS defining illness, refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method. |
| Incidence Rates of Serious Non- AIDS Defining Cardiovascular, Renal or Hepatic Event | From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). | Serious non - AIDS defining cardiovascular, renal, or hepatic event, or death refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method. |
| Incidence Rate of Deaths | From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). | The incidence rate was obtained by using the Kaplan-Meier method. |
| Incidence Rate of HIV/AIDS Related Events | From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). | HIV/AIDS related events refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method. |
| Medication Adherence - Missed Dose Within Past 4 Days | week 0, 48 and 96 | Medication adherence was evaluated by a self reported questionnaire. The number of participants who indicated predefined choice is provided. |
| Incidence Rate of HIV/AIDS Related Events or Death | From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). | HIV/AIDS related events or death refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method. |
| Incidence Rate of HIV/AIDS Related Events or WHO Clinical Stage 2 or 3 Events | From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). | HIV/AIDS related events or WHO Clinical Stage 2 or 3 events refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method. |
| Incidence Rate of Grade 2 and Above Toxicity | All laboratory measures were done at entry,4 and 12 weeks after, and then every 3 months until study end. Signs and Symptoms were recorded from study entry to study end. All were followed until July 7, 2015 (an average of 125 weeks of follow-up) | The toxicity events included all grade 2 and higher hematology or chemistry events and grade 3 or 4 sign or symptoms. These events were graded using the Division of AIDS (DAIDS AE Grading Table), Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com). The incidence rate was obtained by using the Kaplan-Meier method. |
| Incidence Rate of Cardiovascular or Other Metabolic Events | From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). | This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. Given the results of the primary analyses it was decided that this outcome was no longer scientifically important. No resources and funding was allocated by NIH. |
| Incidence Rate of Other Targeted Medical Conditions | From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). | This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. Given the results of the primary analyses it was decided that this outcome was no longer scientifically important. No resources and funding was allocated by NIH. |
| Medication Adherence - How Often Follow Instructions | week 0, 48 and 96 | Medication adherence was evaluated by a self reported questionnaire. The number of participants who indicated predefined choice is provided. |
| Incidence Rate of Any Condition Outlined in Appendix II of Protocol or Death | From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). | This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. Given the results of the primary analyses it was decided that this outcome was no longer scientifically important. No resources and funding was allocated by NIH. |
| Number of Virologic Failure (VF) Participants With HIV Resistance in the Continue HAART Arm | At time of confirmation of VF. HIV-1 RNA testing to identify VF was done at week 4, 12, 24, and every 12 weeks thereafter until study end at an average of 125 weeks. If HIV-1 RNA was above 1000 copies/ml, confirmatory testing was done within 4 weeks. | VF was defined as two successive measurements of HIV-1 RNA above 1000 copies/ml at or after 24 weeks of HAART. HIV drug resistance was defined using the Stanford database (Version 6.2) |
| Medication Adherence - Last Time Missed Medications | week 0, 48 and 96 | Medication adherence was evaluated by a self reported questionnaire. The number of participants who indicated predefined choice is provided. |
| Medication Adherence - How Closely Followed Schedule | week 0, 48 and 96 | Medication adherence was evaluated by a self reported questionnaire. The number of participants who indicated predefined choice is provided. |
| Quality of Life - General Health Outcome | week 0, 48 and 96 | Quality of Life was evaluated by a self reported questionnaire. The number of participants who indicated predefined choice is provided. |
| Quality of Life (QoL) - Health Rating Score | week 0, 48 and 96 | QoL - health rating score was evaluated by a self reported questionnaire. Health rating score of 0 was indicative of death or worst possible health and a score of 100 was being in perfect or best possible health and the mean of score is calculated. Higher scores indicate better Quality of Life (QoL). The range is 0-100 units on a scale |
| Changes in Plasma Concentrations of Inflammatory and Thrombogenic Markers | Measured at baseline, after 4 and 12 weeks, and then every 6 months until study termination. All participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). | This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. This outcome required additional funding for laboratory testing which was not available and so this outcome is not reported. |
| Cost Effectiveness and Feasibility of Treatment Models | Measured at baseline, after 4 - 12 and 24 weeks, and then every 6 months until study termination. All participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). | This outcome was intended as an exploratory analyses and was not included in the primary analyses. Given the results of the primary analyses and changes in WHO guidelines to recommend lifelong antiretroviral therapy, the protocol team decided that this outcome was no longer scientifically important. No resources and funding was allocated by NIH. |
Countries
Argentina, Botswana, Brazil, China, Haiti, Peru, Puerto Rico, Thailand, United States
Participant flow
Recruitment details
There were 1653 participants randomized to the study with enrollments from the US, Argentina, Botswana, Brazil, China, Haiti, and Thailand. The first participant was randomized on January 2010. The last participant was randomized in November 2014.
Pre-assignment details
There were 1917 participants screened for the study, 264 of these failed screening and were not enrolled. The most common reasons for screening failure were CD4 cell count out of range, did not return for consent, test results unavailable on protocol specified time frame, not willing to participate, and not willing to remain on antiretrovirals.
Participants by arm
| Arm | Count |
|---|---|
| Continue HAART Continue receiving HAART within 0-42 days after delivery or other pregnancy outcome. | 827 |
| Stop HAART Stop receiving HAART within 0-42 days after delivery or other pregnancy outcome and resume HAART when protocol specified criteria were met. | 825 |
| Total | 1,652 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 4 |
| Overall Study | Lost to Follow-up | 45 | 39 |
| Overall Study | Site closed | 55 | 52 |
| Overall Study | Withdrawal by Subject | 35 | 31 |
Baseline characteristics
| Characteristic | Total | Stop HAART | Continue HAART |
|---|---|---|---|
| Age, Categorical <=18 years | 36 Participants | 18 Participants | 18 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1616 Participants | 807 Participants | 809 Participants |
| Age, Continuous | 28 years | 28 years | 27 years |
| ART regimen prior to entry HAART including boosted PI | 1241 Participants | 612 Participants | 629 Participants |
| ART regimen prior to entry HAART including II | 8 Participants | 4 Participants | 4 Participants |
| ART regimen prior to entry HAART including NNRTI and PI | 1 Participants | 0 Participants | 1 Participants |
| ART regimen prior to entry HAART including NNRTI [EFV] | 352 Participants | 172 Participants | 180 Participants |
| ART regimen prior to entry HAART including NNRTI [NVP] | 12 Participants | 8 Participants | 4 Participants |
| ART regimen prior to entry HAART including NNRTI [RPV] | 2 Participants | 1 Participants | 1 Participants |
| ART regimen prior to entry HAART including non-boosted PI | 28 Participants | 16 Participants | 12 Participants |
| ART regimen prior to entry HAART including PI and II | 2 Participants | 0 Participants | 2 Participants |
| ART regimen prior to entry Three or more NRTIs | 14 Participants | 11 Participants | 3 Participants |
| ART regimen prior to entry Zero NRTIs | 1 Participants | 1 Participants | 0 Participants |
| Body Mass Index (BMI) | 24.5 kg/m^2 | 24.6 kg/m^2 | 24.4 kg/m^2 |
| CD4+ cell count on ART | 696 cells/mm^3 | 695 cells/mm^3 | 696 cells/mm^3 |
| Duration of Antiretroviral therapy (ART) prior to study entry | 17 weeks | 17 weeks | 17 weeks |
| Hepatitis B surface antibody Indeterminate | 3 Participants | 2 Participants | 1 Participants |
| Hepatitis B surface antibody Negative | 849 Participants | 425 Participants | 424 Participants |
| Hepatitis B surface antibody Not obtained, Hep B antibody +ve | 286 Participants | 148 Participants | 138 Participants |
| Hepatitis B surface antibody Positive | 511 Participants | 248 Participants | 263 Participants |
| Hepatitis B surface antigen Indeterminate | 1 Participants | 0 Participants | 1 Participants |
| Hepatitis B surface antigen Negative | 1539 Participants | 768 Participants | 771 Participants |
| Hepatitis B surface antigen Not obtained, Hep B antibody +ve | 43 Participants | 23 Participants | 20 Participants |
| Hepatitis B surface antigen Positive | 57 Participants | 28 Participants | 29 Participants |
| Plasma HIV Viral Load >=100000 copies/ml | 1 Participants | 0 Participants | 1 Participants |
| Plasma HIV Viral Load 10000-<100000 copies/ml | 39 Participants | 24 Participants | 15 Participants |
| Plasma HIV Viral Load 1000- <10000 copies/ml | 61 Participants | 29 Participants | 32 Participants |
| Plasma HIV Viral Load 400 - <1000 copies/ml | 54 Participants | 24 Participants | 30 Participants |
| Plasma HIV Viral Load < 400 copies/ml | 1486 Participants | 742 Participants | 744 Participants |
| Pre-ART CD4+ cell count | 549 cells/mm^3 | 548 cells/mm^3 | 550 cells/mm^3 |
| Race/Ethnicity Alaskan Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity American Indian | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity Asian | 412 Participants | 203 Participants | 209 Participants |
| Race/Ethnicity Black African | 457 Participants | 227 Participants | 230 Participants |
| Race/Ethnicity Black of African origin | 147 Participants | 70 Participants | 77 Participants |
| Race/Ethnicity Black or African American | 116 Participants | 58 Participants | 58 Participants |
| Race/Ethnicity Mestizo | 14 Participants | 8 Participants | 6 Participants |
| Race/Ethnicity Mixed Black | 149 Participants | 76 Participants | 73 Participants |
| Race/Ethnicity Mixed native | 4 Participants | 4 Participants | 0 Participants |
| Race/Ethnicity Native (native Brazilian-Xavante/Kaigang/Guarani) | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity Other | 62 Participants | 31 Participants | 31 Participants |
| Race/Ethnicity Race not available to clinic | 30 Participants | 16 Participants | 14 Participants |
| Race/Ethnicity Subject does not know | 6 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity White | 250 Participants | 127 Participants | 123 Participants |
| Region of Enrollment Argentina | 45 Participants | 25 Participants | 20 Participants |
| Region of Enrollment Botswana | 457 Participants | 227 Participants | 230 Participants |
| Region of Enrollment Brazil | 514 Participants | 255 Participants | 259 Participants |
| Region of Enrollment China | 104 Participants | 52 Participants | 52 Participants |
| Region of Enrollment Haiti | 61 Participants | 29 Participants | 32 Participants |
| Region of Enrollment Peru | 15 Participants | 9 Participants | 6 Participants |
| Region of Enrollment Thailand | 307 Participants | 151 Participants | 156 Participants |
| Region of Enrollment United States | 149 Participants | 77 Participants | 72 Participants |
| Sex: Female, Male Female | 1652 Participants | 825 Participants | 827 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| WHO stage at entry Clinical Stage I | 1621 Participants | 811 Participants | 810 Participants |
| WHO stage at entry Clinical Stage II | 27 Participants | 11 Participants | 16 Participants |
| WHO stage at entry Clinical Stage III | 2 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 827 | 4 / 825 |
| other Total, other adverse events | 778 / 827 | 765 / 825 |
| serious Total, serious adverse events | 10 / 827 | 3 / 825 |
Outcome results
Primary
Incidence Rates of AIDS - Defining Illness, Serious Non-AIDS Defining, Cardiovascular, Renal, Hepatic Event, or Death
AIDS defining illness, serious non-AIDS defining cardiovascular, renal, or hepatic event, or death refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method.
Time frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
Population: All participants except one who was excluded as she withdrew from study on the day she was randomized
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continue HAART | Incidence Rates of AIDS - Defining Illness, Serious Non-AIDS Defining, Cardiovascular, Renal, Hepatic Event, or Death | 0.21 New cases per 100 person - years |
| Stop HAART | Incidence Rates of AIDS - Defining Illness, Serious Non-AIDS Defining, Cardiovascular, Renal, Hepatic Event, or Death | 0.31 New cases per 100 person - years |
p-value: 0.5495% CI: [0.19, 2.4]Log Rank
Secondary
Changes in Plasma Concentrations of Inflammatory and Thrombogenic Markers
This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. This outcome required additional funding for laboratory testing which was not available and so this outcome is not reported.
Time frame: Measured at baseline, after 4 and 12 weeks, and then every 6 months until study termination. All participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
Population: This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. This outcome required additional funding for laboratory testing which was not available and so this outcome is not reported.
Secondary
Cost Effectiveness and Feasibility of Treatment Models
This outcome was intended as an exploratory analyses and was not included in the primary analyses. Given the results of the primary analyses and changes in WHO guidelines to recommend lifelong antiretroviral therapy, the protocol team decided that this outcome was no longer scientifically important. No resources and funding was allocated by NIH.
Time frame: Measured at baseline, after 4 - 12 and 24 weeks, and then every 6 months until study termination. All participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
Population: This outcome was intended as an exploratory analyses and was not included in the primary analyses. Given the results of the primary analyses and changes in WHO guidelines to recommend lifelong antiretroviral therapy, the protocol team decided that this outcome was no longer scientifically important. No resources and funding was allocated by NIH.
Secondary
Incidence Rate of AIDS - Defining Illness
AIDS defining illness, refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method.
Time frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
Population: All participants except one who was excluded as she withdrew from study on the day she was randomized
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continue HAART | Incidence Rate of AIDS - Defining Illness | 0.10 New cases per 100 person - years |
| Stop HAART | Incidence Rate of AIDS - Defining Illness | 0.15 New cases per 100 person - years |
p-value: 0.6695% CI: [0.11, 4.01]Log Rank
Secondary
Incidence Rate of Any Condition Outlined in Appendix II of Protocol or Death
This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. Given the results of the primary analyses it was decided that this outcome was no longer scientifically important. No resources and funding was allocated by NIH.
Time frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
Population: This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. Given the results of the primary analyses it was decided that this outcome was no longer scientifically important. No resources and funding was allocated by NIH.
Secondary
Incidence Rate of Cardiovascular or Other Metabolic Events
This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. Given the results of the primary analyses it was decided that this outcome was no longer scientifically important. No resources and funding was allocated by NIH.
Time frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
Population: This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. Given the results of the primary analyses it was decided that this outcome was no longer scientifically important. No resources and funding was allocated by NIH.
Secondary
Incidence Rate of Deaths
The incidence rate was obtained by using the Kaplan-Meier method.
Time frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
Population: All participants except one who was excluded as she withdrew from study on the day she was randomized
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continue HAART | Incidence Rate of Deaths | 0.10 New cases per 100 person - years |
| Stop HAART | Incidence Rate of Deaths | 0.20 New cases per 100 person - years |
p-value: 0.4495% CI: [0.09, 2.81]Log Rank
Secondary
Incidence Rate of Grade 2 and Above Toxicity
The toxicity events included all grade 2 and higher hematology or chemistry events and grade 3 or 4 sign or symptoms. These events were graded using the Division of AIDS (DAIDS AE Grading Table), Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com). The incidence rate was obtained by using the Kaplan-Meier method.
Time frame: All laboratory measures were done at entry,4 and 12 weeks after, and then every 3 months until study end. Signs and Symptoms were recorded from study entry to study end. All were followed until July 7, 2015 (an average of 125 weeks of follow-up)
Population: All participants except one who was excluded as she withdrew from study on the day she was randomized
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continue HAART | Incidence Rate of Grade 2 and Above Toxicity | 18.4 New cases per 100 person - years |
| Stop HAART | Incidence Rate of Grade 2 and Above Toxicity | 15.6 New cases per 100 person - years |
p-value: 0.195% CI: [0.72, 1.03]Log Rank
Secondary
Incidence Rate of HIV/AIDS Related Events
HIV/AIDS related events refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method.
Time frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
Population: All participants except one who was excluded as she withdrew from study on the day she was randomized
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continue HAART | Incidence Rate of HIV/AIDS Related Events | 1.32 New cases per 100 person - years |
| Stop HAART | Incidence Rate of HIV/AIDS Related Events | 1.42 New cases per 100 person - years |
p-value: 0.7995% CI: [0.54, 1.6]Log Rank
Secondary
Incidence Rate of HIV/AIDS Related Events or Death
HIV/AIDS related events or death refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method.
Time frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
Population: All participants except one who was excluded as she withdrew from study on the day she was randomized
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continue HAART | Incidence Rate of HIV/AIDS Related Events or Death | 1.42 New cases per 100 person - years |
| Stop HAART | Incidence Rate of HIV/AIDS Related Events or Death | 1.57 New cases per 100 person - years |
p-value: 0.7195% CI: [0.54, 1.52]Log Rank
Secondary
Incidence Rate of HIV/AIDS Related Events or WHO Clinical Stage 2 or 3 Events
HIV/AIDS related events or WHO Clinical Stage 2 or 3 events refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method.
Time frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
Population: All participants except one who was excluded as she withdrew from study on the day she was randomized
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continue HAART | Incidence Rate of HIV/AIDS Related Events or WHO Clinical Stage 2 or 3 Events | 3.09 New cases per 100 person - years |
| Stop HAART | Incidence Rate of HIV/AIDS Related Events or WHO Clinical Stage 2 or 3 Events | 5.37 New cases per 100 person - years |
p-value: <0.00195% CI: [0.42, 0.8]Log Rank
Secondary
Incidence Rate of Other Targeted Medical Conditions
This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. Given the results of the primary analyses it was decided that this outcome was no longer scientifically important. No resources and funding was allocated by NIH.
Time frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
Population: This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. Given the results of the primary analyses it was decided that this outcome was no longer scientifically important. No resources and funding was allocated by NIH.
Secondary
Incidence Rates of Serious Non- AIDS Defining Cardiovascular, Renal or Hepatic Event
Serious non - AIDS defining cardiovascular, renal, or hepatic event, or death refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method.
Time frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
Population: All participants except one who was excluded as she withdrew from study on the day she was randomized
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continue HAART | Incidence Rates of Serious Non- AIDS Defining Cardiovascular, Renal or Hepatic Event | 0 New cases per 100 person - years |
| Stop HAART | Incidence Rates of Serious Non- AIDS Defining Cardiovascular, Renal or Hepatic Event | 0 New cases per 100 person - years |
Secondary
Medication Adherence - How Closely Followed Schedule
Medication adherence was evaluated by a self reported questionnaire. The number of participants who indicated predefined choice is provided.
Time frame: week 0, 48 and 96
Population: Participants in the Continue HAART arm who had evaluations done at the respective weeks
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Continue HAART | Medication Adherence - How Closely Followed Schedule | Week 0 | Never | 23 Participants |
| Continue HAART | Medication Adherence - How Closely Followed Schedule | Week 0 | Some of the time | 130 Participants |
| Continue HAART | Medication Adherence - How Closely Followed Schedule | Week 0 | All of the time | 520 Participants |
| Continue HAART | Medication Adherence - How Closely Followed Schedule | Week 48 | Never | 17 Participants |
| Continue HAART | Medication Adherence - How Closely Followed Schedule | Week 48 | Some of the time | 173 Participants |
| Continue HAART | Medication Adherence - How Closely Followed Schedule | Week 48 | All of the time | 461 Participants |
| Continue HAART | Medication Adherence - How Closely Followed Schedule | Week 96 | Never | 25 Participants |
| Continue HAART | Medication Adherence - How Closely Followed Schedule | Week 96 | Some of the time | 153 Participants |
| Continue HAART | Medication Adherence - How Closely Followed Schedule | Week 96 | All of the time | 459 Participants |
Secondary
Medication Adherence - How Often Follow Instructions
Medication adherence was evaluated by a self reported questionnaire. The number of participants who indicated predefined choice is provided.
Time frame: week 0, 48 and 96
Population: Participants in the Continue HAART arm who had evaluations done at the respective weeks
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Continue HAART | Medication Adherence - How Often Follow Instructions | Week 0 | Never | 10 Participants |
| Continue HAART | Medication Adherence - How Often Follow Instructions | Week 0 | Some of the time | 52 Participants |
| Continue HAART | Medication Adherence - How Often Follow Instructions | Week 0 | All of the time | 166 Participants |
| Continue HAART | Medication Adherence - How Often Follow Instructions | Week 0 | No special instructions | 439 Participants |
| Continue HAART | Medication Adherence - How Often Follow Instructions | Week 48 | Never | 6 Participants |
| Continue HAART | Medication Adherence - How Often Follow Instructions | Week 48 | Some of the time | 61 Participants |
| Continue HAART | Medication Adherence - How Often Follow Instructions | Week 48 | All of the time | 194 Participants |
| Continue HAART | Medication Adherence - How Often Follow Instructions | Week 48 | No special instructions | 389 Participants |
| Continue HAART | Medication Adherence - How Often Follow Instructions | Week 96 | Never | 8 Participants |
| Continue HAART | Medication Adherence - How Often Follow Instructions | Week 96 | Some of the time | 74 Participants |
| Continue HAART | Medication Adherence - How Often Follow Instructions | Week 96 | All of the time | 190 Participants |
| Continue HAART | Medication Adherence - How Often Follow Instructions | Week 96 | No special instructions | 365 Participants |
Secondary
Medication Adherence - Last Time Missed Medications
Medication adherence was evaluated by a self reported questionnaire. The number of participants who indicated predefined choice is provided.
Time frame: week 0, 48 and 96
Population: Participants in the Continue HAART arm who had evaluations done at the respective weeks
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Continue HAART | Medication Adherence - Last Time Missed Medications | Week 0 | Never skipped medications | 489 Participants |
| Continue HAART | Medication Adherence - Last Time Missed Medications | Week 0 | More than 1 month ago | 60 Participants |
| Continue HAART | Medication Adherence - Last Time Missed Medications | Week 0 | Within the past 4 weeks | 123 Participants |
| Continue HAART | Medication Adherence - Last Time Missed Medications | Week 48 | Never skipped medications | 411 Participants |
| Continue HAART | Medication Adherence - Last Time Missed Medications | Week 48 | More than 1 month ago | 97 Participants |
| Continue HAART | Medication Adherence - Last Time Missed Medications | Week 48 | Within the past 4 weeks | 144 Participants |
| Continue HAART | Medication Adherence - Last Time Missed Medications | Week 96 | Never skipped medications | 399 Participants |
| Continue HAART | Medication Adherence - Last Time Missed Medications | Week 96 | More than 1 month ago | 92 Participants |
| Continue HAART | Medication Adherence - Last Time Missed Medications | Week 96 | Within the past 4 weeks | 147 Participants |
Secondary
Medication Adherence - Missed Dose Within Past 4 Days
Medication adherence was evaluated by a self reported questionnaire. The number of participants who indicated predefined choice is provided.
Time frame: week 0, 48 and 96
Population: Participants in the Continue HAART arm who had evaluations done at the respective weeks
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Continue HAART | Medication Adherence - Missed Dose Within Past 4 Days | Week 0 | No | 592 Participants |
| Continue HAART | Medication Adherence - Missed Dose Within Past 4 Days | Week 0 | Yes | 61 Participants |
| Continue HAART | Medication Adherence - Missed Dose Within Past 4 Days | Week 48 | No | 564 Participants |
| Continue HAART | Medication Adherence - Missed Dose Within Past 4 Days | Week 48 | Yes | 71 Participants |
| Continue HAART | Medication Adherence - Missed Dose Within Past 4 Days | Week 96 | No | 544 Participants |
| Continue HAART | Medication Adherence - Missed Dose Within Past 4 Days | Week 96 | Yes | 77 Participants |
Secondary
Number of Virologic Failure (VF) Participants With HIV Resistance in the Continue HAART Arm
VF was defined as two successive measurements of HIV-1 RNA above 1000 copies/ml at or after 24 weeks of HAART. HIV drug resistance was defined using the Stanford database (Version 6.2)
Time frame: At time of confirmation of VF. HIV-1 RNA testing to identify VF was done at week 4, 12, 24, and every 12 weeks thereafter until study end at an average of 125 weeks. If HIV-1 RNA was above 1000 copies/ml, confirmatory testing was done within 4 weeks.
Population: 156 women who were VFs had antiretroviral drug resistance testing performed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Continue HAART | Number of Virologic Failure (VF) Participants With HIV Resistance in the Continue HAART Arm | 19 Participants |
Secondary
Quality of Life - General Health Outcome
Quality of Life was evaluated by a self reported questionnaire. The number of participants who indicated predefined choice is provided.
Time frame: week 0, 48 and 96
Population: All participants except one who was excluded as she withdrew from study on the day she was randomized
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Continue HAART | Quality of Life - General Health Outcome | week 0 | Excellent | 160 Participants |
| Continue HAART | Quality of Life - General Health Outcome | week 48 | Fair | 52 Participants |
| Continue HAART | Quality of Life - General Health Outcome | week 0 | Poor | 3 Participants |
| Continue HAART | Quality of Life - General Health Outcome | week 48 | Poor | 5 Participants |
| Continue HAART | Quality of Life - General Health Outcome | week 0 | Good | 327 Participants |
| Continue HAART | Quality of Life - General Health Outcome | week 96 | Excellent | 131 Participants |
| Continue HAART | Quality of Life - General Health Outcome | week 48 | Excellent | 172 Participants |
| Continue HAART | Quality of Life - General Health Outcome | week 96 | Very good | 179 Participants |
| Continue HAART | Quality of Life - General Health Outcome | week 0 | Very good | 262 Participants |
| Continue HAART | Quality of Life - General Health Outcome | week 96 | Good | 165 Participants |
| Continue HAART | Quality of Life - General Health Outcome | week 48 | Very good | 250 Participants |
| Continue HAART | Quality of Life - General Health Outcome | week 96 | Fair | 23 Participants |
| Continue HAART | Quality of Life - General Health Outcome | week 0 | Fair | 71 Participants |
| Continue HAART | Quality of Life - General Health Outcome | week 96 | Poor | 2 Participants |
| Continue HAART | Quality of Life - General Health Outcome | week 48 | Good | 222 Participants |
| Stop HAART | Quality of Life - General Health Outcome | week 96 | Poor | 1 Participants |
| Stop HAART | Quality of Life - General Health Outcome | week 0 | Excellent | 164 Participants |
| Stop HAART | Quality of Life - General Health Outcome | week 0 | Very good | 269 Participants |
| Stop HAART | Quality of Life - General Health Outcome | week 0 | Good | 333 Participants |
| Stop HAART | Quality of Life - General Health Outcome | week 0 | Fair | 51 Participants |
| Stop HAART | Quality of Life - General Health Outcome | week 0 | Poor | 1 Participants |
| Stop HAART | Quality of Life - General Health Outcome | week 48 | Excellent | 185 Participants |
| Stop HAART | Quality of Life - General Health Outcome | week 48 | Very good | 229 Participants |
| Stop HAART | Quality of Life - General Health Outcome | week 48 | Good | 238 Participants |
| Stop HAART | Quality of Life - General Health Outcome | week 48 | Fair | 48 Participants |
| Stop HAART | Quality of Life - General Health Outcome | week 48 | Poor | 1 Participants |
| Stop HAART | Quality of Life - General Health Outcome | week 96 | Excellent | 134 Participants |
| Stop HAART | Quality of Life - General Health Outcome | week 96 | Very good | 178 Participants |
| Stop HAART | Quality of Life - General Health Outcome | week 96 | Good | 157 Participants |
| Stop HAART | Quality of Life - General Health Outcome | week 96 | Fair | 34 Participants |
Secondary
Quality of Life (QoL) - Health Rating Score
QoL - health rating score was evaluated by a self reported questionnaire. Health rating score of 0 was indicative of death or worst possible health and a score of 100 was being in perfect or best possible health and the mean of score is calculated. Higher scores indicate better Quality of Life (QoL). The range is 0-100 units on a scale
Time frame: week 0, 48 and 96
Population: All participants except one who was excluded as she withdrew from study on the day she was randomized
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Continue HAART | Quality of Life (QoL) - Health Rating Score | week 0 | 82.7 units on a scale | Standard Deviation 15.7 |
| Continue HAART | Quality of Life (QoL) - Health Rating Score | week 48 | 85.3 units on a scale | Standard Deviation 14.7 |
| Continue HAART | Quality of Life (QoL) - Health Rating Score | week 96 | 86.2 units on a scale | Standard Deviation 14.1 |
| Stop HAART | Quality of Life (QoL) - Health Rating Score | week 0 | 83.0 units on a scale | Standard Deviation 15.1 |
| Stop HAART | Quality of Life (QoL) - Health Rating Score | week 48 | 85.4 units on a scale | Standard Deviation 14 |
| Stop HAART | Quality of Life (QoL) - Health Rating Score | week 96 | 86.3 units on a scale | Standard Deviation 14 |