Acute HIV Infection, HIV Infections
Conditions
Keywords
Acute HIV, HIV, Treatment Naive, Acute Infections
Brief summary
Purpose: This is a pilot study to evaluate HIV viremia and persistence in acutely HIV infected antiretroviral naïve patients treated with Darunavir/ritonavir and Etravirine Participants: 20 participants, age 18 and older, HIV infected, antiretroviral naïve patients Procedures (methods): ARV treatment with Darunavir/ritonavir and Etravirine, Optional studies: Genital secretion samples, Cerebrospinal fluid samples, Leukapheresis, Endoscopy/colonoscopy
Detailed description
Study Design This is a multicenter, single arm, 48-week open-label pilot study of DRV/R & ETR in acute HIV infection. Study sites will be members of the Duke-UNC Acute HIV Infection Study Consortium. If baseline resistance is detected after treatment begins (e.g. evidence of pre-existing baseline resistance (genotypic or phenotypic) that may adversely affect the efficacy of the study regimen), the patient may elect to alter treatment as per best clinical practice. The new regimen will not be provided by the study, but will be obtained for the participant through available clinical resources. After patients are identified with acute HIV infection, they will be offered the opportunity to participate in the study. Patients will also be offered the opportunity to co-enroll in CHAVI 001 and 012, studies that follow the virological and immunological response of patients with AHI, regardless of the initiation of ART. An overall consent form will be signed for study participation, and separate informed consents with signatures will be obtained for optional studies. Patients will be eligible for participation after signing the overall consent - agreeing to participate in studies of other compartment specimens is not required for enrollment. At the initial visit, patient eligibility will be confirmed with appropriate laboratory testing (see STUDY POPULATION). When eligibility is verified, entry laboratory studies will be obtained, and the participants will be started on DRV/r, and ETR. All participants will be followed at regular intervals thereafter as specified in the schedule of evaluations. Participants meeting criteria for virologic failure will be offered the opportunity to switch to the best available regimen as selected by their HIV provider. Hypothesis Combination therapy with DRV/R & ETR will suppress plasma viremia and improve immunologic function in antiretroviral (ART)-naïve, acutely HIV-infected (AHI) patients, and will limit replication in HIV-1 cellular compartments.
Interventions
DRUGDarunavir
800 mg orally once daily
DRUGRitonavir
100 mg orally once daily
DRUGEtravirine
200 mg orally twice daily, although patients may choose to take ETR 400 mg QD to have a simpler all QD regimen
Sponsors
Janssen Pharmaceuticals
University of North Carolina, Chapel Hill
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Documentation of Acute HIV Infection as defined above. 2. Men and women age ≥18 years. 3. Participants will be ART naïve, defined as ≤14 days of antiretroviral treatment at any time prior to entry. The only exceptions are: Post-exposure prophylaxis (PEP) provided the patient was documented as HIV-1 negative at least 3-6 months after completion of the PEP treatment. 4. Screening HIV-1 RNA \>1,000 copies/mL obtained within 30 days at study entry. 5. Lab values obtained within 30 days prior to study entry: 6. Absolute neutrophil count \>500/mm3 7. Hemoglobin \> 8.5 g/dL for men and \> 8.0 g/dL for women 8. Platelet count \>50,000/mm3 9. AST (SGOT) ≤2.5 x ULN 10. ALT (SGPT) ≤2.5 x ULN 11. Total bilirubin \<2.5 x ULN 12. Calculated creatinine clearance (Cockcroft-Gault formula) \> 30mL/min: * CrCl = (140-age) x body weight (kg) (x 0.85 if female) * Serum creatinine \[mg/dL\] x (72) 13. For women of reproductive potential, a negative serum or urine pregnancy test within 7 days prior to initiating antiretroviral study medications. Reproductive potential is defined as females who have reached menarche and have not been post-menopausal for at least 24 consecutive months, or have not undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, or salpingotomy). Acceptable documentation of surgical sterilization includes patient-reported history. 14. If participating in sexual activity that could lead to pregnancy, female study patients must use at least one form of contraception, which could consist only of a barrier method. All patients must continue to use contraception for 6 weeks after stopping the study medications. Acceptable methods of contraception include: condoms (male or female) with or without spermicidal agent, diaphragm or cervical cap with spermicide, or IUD. Female volunteers not of reproductive potential are not required to use contraception. 15. Ability and willingness of patient to give written informed consent.
Exclusion criteria
1. Women who are pregnant or breast-feeding. 2. Women with a positive pregnancy test on enrollment or prior to study drug administration. 3. Women of reproductive potential who are unwilling or unable to use acceptable methods to avoid pregnancy for the entire study period 4. Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. * Prednisone at a daily dose of 10 mg or less (physiologic replacement dose) is permitted. 5. Known allergy/sensitivity to study drugs or their formulations. 6. Difficulty swallowing capsules/tablets. 7. Inability to communicate effectively with study personnel. 8. Incarceration; prisoner recruitment and participation are not permitted. 9. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements or confound the analysis of study endpoints. 10. Any active psychiatric illness including schizophrenia, severe depression, or severe bipolar affective disorder that, in the opinion of the investigator, could confound the analysis of the neurological examination or neuropsychological test results. 11. Active brain infection (except for HIV-1), brain neoplasm, space-occupying brain lesion requiring acute or chronic therapy. Participants with any fungal meningitis, parasitic infection, or CNS lymphoma are excluded from participation. 12. Serious illness requiring systemic treatment and/or hospitalization until patient either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry. NOTE: Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as judged by the site investigator) have no restriction. 13. Known cardiac conduction disease. 14. Prior treatment with any other experimental drug for any indication (within 30 days of initiating study treatment). 15. Unable to discontinue any current medications that are excluded during study treatment. 16. A life expectancy less than twelve months. 17. Acute Viral Hepatitis, including, but not limited to, Hepatitis A, B, or C 18. Chronic Hepatitis B Infection documented by a detectable serum Hepatitis B surface antigen (HBsAg) or plasma HBV DNA
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Virologic Response | 24 weeks | Virologic response defined as plasma HIV RNA measurement \<200 copies/mL at week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Darunavir Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure | between Week 4-12 and between Weeks 36-48 | — |
| Minimum Darunavir Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure | between week 4-12 and between weeks 36-48 | — |
| Maximum Ritonavir Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure | between week 4-12 and between Weeks 36-48 | — |
| Minimum Ritonavir Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure | between week 4-12 and between weeks 36-48 | — |
| Number of Participants With HIV RNA Measurement Above the Limits of Detection in Cerebrospinal Fluid | Week 4 and Week 48 | — |
| Number of Participants With Neurocognitive Impairment at Baseline | Week 2 or 4 | — |
| Number of Participants With Neurocognitive Impairment at Week 24 | Week 24 | — |
| Number of Participants With Neurocognitive Impairment at Week 48 | Week 48 | — |
| Overall Neurocognitive Impairment Score at Week 2 or 4 | Week 2 or 4 | Neuropsychological performance was assessed at Week 2 or 4, Week 24 and Week 48 in the following measures: Premorbid/language (Wide Range Achievement Test 4 -Reading Subtest), Learning (HVLT-R, Hopkins Verbal Learning Test-Revised), Memory (HVLT-R), Speed of Processing (Trailmaking A (Army Individual Test Battery, 1944), 1974, Stroop color, Attention (WAIS-III Symbol Search; Stroop word, Fine motor, Executive (Trailmaking B, Stroop interference, Letter, Category Fluency. An overall summary score was created by averaging all tests. Participants also completed the self-reported functional status Patient's Assessment of Own Functioning Inventory (PAOFI) and the Activities of Daily Living Scale (ADLS). Best available demographically corrected normative data were utilized to create z scores. A negative z score denotes below-average performance relative to a US normative comparison population. A higher z score is a better outcome. |
| Overall Neurocognitive Impairment at Week 24 | Week 24 | Neuropsychological performance was assessed at week 2 or 4, week 24 and week 48 in the following measures: Premorbid/language (Wide Range Achievement Test 4 -Reading Subtest), Learning (Hopkins Verbal Learning Test - Revised), Memory (HVLT-R), Speed of Processing (Trailmaking A (Army Individual Test Battery, 1944), 1974, Stroop color, Attention (WAIS-III Symbol Search; Stroop word, Fine motor, Executive (Trailmaking B, Stroop interference, Letter, Category Fluency. An overall summary score of neurocognitive functioning was created by averaging all tests. Participants also completed Patient's Assessment of Own Functioning Inventory (PAOFI) and the Activities of Daily Living Scale (ADLS). Best available demographically corrected normative data were utilized to create z scores. A negative z score denotes below-average performance relative to a US normative comparison population. A higher z score is a better outcome. |
| Overall Neurocognitive Impairment at Week 48 | Week 48 | Neuropsychological performance was assessed at baseline (week 2 or 4), week 24 and week 48 in the following domain (measures): Premorbid/language (Wide Range Achievement Test (WRAT) 4 - Reading Subtest), Learning (HVLT-R, Hopkins Verbal Learning Test - Revised), Memory (HVLT-R), Speed of Processing (Trailmaking A (Army Individual Test Battery, 1944), 1974, Stroop color, Attention (WAIS-III Symbol Search; Stroop word, Fine motor, Executive (Trailmaking B, Stroop interference, Letter, Category Fluency. An overall summary score of neurocognitive functioning was created by averaging all tests. Participants also completed the self-reported functional status Patient's Assessment of Own Functioning Inventory (PAOFI) and the Activities of Daily Living Scale (ADLS). Best available demographically corrected normative data were utilized to create z scores. A negative z score denotes below-average performance relative to a US normative comparison population. A higher z score is a better outcome. |
| Change in Overall Neurocognitive Impairment From Baseline to Week 24 or 48 | Baseline to Week 24 or 48 | Change in overall z score from baseline to week 24 or 48. A negative z score denotes below-average performance relative to a US normative comparison population. A higher z score is a better outcome. |
| Correlation of HIV RNA Levels in CSF and Drug Levels With Neurocognitive Functioning | From enrollment through Week 48 | — |
| Correlation of Time to HIV RNA Levels <200 Copies/mL With Improvement in Neurocognitive Functioning From Baseline to Week 24 and 48 | Baseline to Week 24 and 48 | — |
| HIV RNA Detection in Ileal Biopsy Specimens | Weeks 4 and 48 | Average HIV RNA detected in the ileal biopsy specimens per participant over weeks 4 and 48. |
| Number of Participants With Virologic Response | 48 weeks from enrollment | Virologic response to study treatment defined as plasma HIV RNA measurement \<50 copies/mL at week 48 |
| Median Change in CD4 Cell Count From Week 0 to Week 24. | week 0, week 24 | — |
| Median Change in CD4 Cell Count From Week 0 to Week 48. | 48 weeks from enrollment | — |
| HIV RNA Levels Immediately Prior to Initiating Study Treatment. | HIV RNA level at enrollment | — |
| Median Time to HIV RNA Suppression to <200 Copies/mL | From enrollment to the date of HIV RNA suppression, assessed up to Week 48 | — |
| HIV RNA Detection in Semen | From enrollment through 48 weeks | Total cumulative levels of HIV RNA detected in the semen of participants from enrollment through week 48. |
| Number of Participants Who Stopped Study Treatment Due to Adverse Event or Intolerance | Enrollment to Week 48 | — |
| Adverse Events Possibly or Definitely Related to Study Treatment Through Week 48 | Enrollment to week 48 | Total number of adverse events observed that were possibly or definitely related to study treatment through week 48 |
| Maximum Etravirine Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture | Week 4 and week 48 | — |
| Minimum Etravirine Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture | Week 4 and week 48 | — |
| Maximum Darunavir Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture | Week 4 and week 48 | — |
| Minimum Darunavir Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture | Week 4 and week 48 | — |
| Maximum Ritonavir Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture | Week 4 and Week 48 | — |
| Minimum Ritonavir Exposure Range in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture | Week 4 and week 48 | — |
| Maximum Etravirine Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen | Weeks 0-4 and weeks 12, 48 | — |
| Minimum Etravirine Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen | Weeks 0-4 and weeks 12, 48 | — |
| Maximum Darunavir Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen | Weeks 0-4 and weeks 12, 48 | — |
| Minimum Darunavir Exposure Range in Semen Among Participants Who Consented to an Optional Collection of Semen | Weeks 0-4 and weeks 12, 48 | — |
| Maximum Ritonavir Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen | Weeks 0-4 and Weeks 12, 48 | — |
| Minimum Ritonavir Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen | Weeks 0-4 and Weeks 12, 48 | — |
| Maximum Etravirine Exposure in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure | between Week 4-12 and between Weeks 36-48 | — |
| Minimum Etravirine Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure | between Week 4-12 and between Weeks 36-48 | — |
Countries
United States
Participant flow
Recruitment details
Individuals diagnosed with acute HIV in clinical sites within 30 days of enrollment and at least 18 years of age were enrolled. Acute HIV defined as: i) negative EIA and positive NAT; ii) positive EIA and positive NAT with negative/indeterminate western blot (WB); or iii) positive EIA, positive WB and EIA negative documentation in prior 30 days.
Participants by arm
| Arm | Count |
|---|---|
| Acute HIV Infection Treatment Group All participants were administered darunavir 800mg, ritonavir 100mg once daily plus etravirine as 400mg once daily or 200mg twice daily started within 30 days of acute HIV diagnosis and continued for 48 weeks. Participants were evaluated on study at weeks 2, 4, 8, 12, 16, 24 and 48. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Acute HIV Infection Treatment Group |
|---|---|
| Age, Continuous Age | 23 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 4 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Number of Participants With Virologic Response
Virologic response defined as plasma HIV RNA measurement \<200 copies/mL at week 24
Time frame: 24 weeks
Population: All participants enrolled were included in analysis of virologic response
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acute HIV Infection Treatment Group | Number of Participants With Virologic Response | 13 Participants |
Secondary
Adverse Events Possibly or Definitely Related to Study Treatment Through Week 48
Total number of adverse events observed that were possibly or definitely related to study treatment through week 48
Time frame: Enrollment to week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Adverse Events Possibly or Definitely Related to Study Treatment Through Week 48 | 13 adverse events |
Secondary
Change in Overall Neurocognitive Impairment From Baseline to Week 24 or 48
Change in overall z score from baseline to week 24 or 48. A negative z score denotes below-average performance relative to a US normative comparison population. A higher z score is a better outcome.
Time frame: Baseline to Week 24 or 48
Population: Participants who underwent neurocognitive assessment at baseline and Week 24 and/or 48.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acute HIV Infection Treatment Group | Change in Overall Neurocognitive Impairment From Baseline to Week 24 or 48 | 4.23 z score | Standard Deviation 0.15 |
Comparison: An overall summary score of neurocognitive functioning was created by averaging all tests. Best available demographically corrected normative data were utilized to create z scores and then deficit scores for impairment ratings.Change in neurocognitive functioning was analyzed using a one sided repeated measures ANOVA with neurocognitive performance as the dependent variable (total z score) and time (visit) as the independent variable. Degrees of freedom were 2,17.p-value: 0.03ANOVA
Secondary
Correlation of HIV RNA Levels in CSF and Drug Levels With Neurocognitive Functioning
Time frame: From enrollment through Week 48
Population: Participants who consented to neurocognitive assessments at baseline and week 24 or 48. Sponsor stopped study prior to target enrollment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Correlation of HIV RNA Levels in CSF and Drug Levels With Neurocognitive Functioning | NA r value |
Secondary
Correlation of Time to HIV RNA Levels <200 Copies/mL With Improvement in Neurocognitive Functioning From Baseline to Week 24 and 48
Time frame: Baseline to Week 24 and 48
Population: Participants who consented to optional neurocognitive assessments at baseline and week 24 or 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Correlation of Time to HIV RNA Levels <200 Copies/mL With Improvement in Neurocognitive Functioning From Baseline to Week 24 and 48 | -.82 r value |
Comparison: Correlation between time (days) to HIV RNA suppression \<200 copies/mL and total z score (mean) was assessed by Spearman correlationp-value: <0.005Spearman correlation
Secondary
HIV RNA Detection in Ileal Biopsy Specimens
Average HIV RNA detected in the ileal biopsy specimens per participant over weeks 4 and 48.
Time frame: Weeks 4 and 48
Population: Study stopped prior to target enrollment by sponsor. Given insufficient ileal biopsy samples, correlation of HIV viremia in ileal biopsies with time to suppression was not performed due to inadequate power to analyze the outcome.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Acute HIV Infection Treatment Group | HIV RNA Detection in Ileal Biopsy Specimens | 40 copies/mL |
Secondary
HIV RNA Detection in Semen
Total cumulative levels of HIV RNA detected in the semen of participants from enrollment through week 48.
Time frame: From enrollment through 48 weeks
Population: Study stopped prior to target enrollment by sponsor. Given insufficient semen samples, correlation of HIV viremia in semen with time to suppression was not performed due to inadequate power to analyze the outcome.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Acute HIV Infection Treatment Group | HIV RNA Detection in Semen | 2541 copies/mL |
Secondary
HIV RNA Levels Immediately Prior to Initiating Study Treatment.
Time frame: HIV RNA level at enrollment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acute HIV Infection Treatment Group | HIV RNA Levels Immediately Prior to Initiating Study Treatment. | 1,000,000 copies/mL |
Secondary
Maximum Darunavir Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture
Time frame: Week 4 and week 48
Population: Four participants consented to 7 optional lumbar puncture to provide CSF sample for measurement of drug levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Maximum Darunavir Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture | 240 ng/mL |
Secondary
Maximum Darunavir Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen
Time frame: Weeks 0-4 and weeks 12, 48
Population: Four participants consented to provide a semen sample for measurement of drug levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Maximum Darunavir Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen | 1296 ng/mL |
Secondary
Maximum Darunavir Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure
Time frame: between Week 4-12 and between Weeks 36-48
Population: Six participants consented to ileal biopsy for measurement of drug levels
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Maximum Darunavir Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure | 83,749 ng/g |
Secondary
Maximum Etravirine Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture
Time frame: Week 4 and week 48
Population: 4 participants consented to 7 optional lumbar punctures to provide CSF samples for measurement of drug levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Maximum Etravirine Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture | 25 ng/mL |
Secondary
Maximum Etravirine Exposure in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure
Time frame: between Week 4-12 and between Weeks 36-48
Population: Six participants consented to ileal biopsy for measurement of drug levels
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Maximum Etravirine Exposure in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure | 83,749 ng/g |
Secondary
Maximum Etravirine Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen
Time frame: Weeks 0-4 and weeks 12, 48
Population: Four participants consented to provide a semen sample for measurement of drug levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Maximum Etravirine Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen | 185 ng/mL |
Secondary
Maximum Ritonavir Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture
Time frame: Week 4 and Week 48
Population: Four participants consented to 7 optional lumbar puncture to provide CSF sample for measurement of drug levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Maximum Ritonavir Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture | 22 ng/mL |
Secondary
Maximum Ritonavir Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen
Time frame: Weeks 0-4 and Weeks 12, 48
Population: Four participants consented to provide a semen sample for measurement of drug levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Maximum Ritonavir Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen | 22 ng/mL |
Secondary
Maximum Ritonavir Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure
Time frame: between week 4-12 and between Weeks 36-48
Population: Six participants consented to ileal biopsy for measurement of drug levels
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Maximum Ritonavir Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure | 14,698 ng/g |
Secondary
Median Change in CD4 Cell Count From Week 0 to Week 24.
Time frame: week 0, week 24
Population: All participants enrolled were included in this analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acute HIV Infection Treatment Group | Median Change in CD4 Cell Count From Week 0 to Week 24. | 158 cells/mm^3 |
Secondary
Median Change in CD4 Cell Count From Week 0 to Week 48.
Time frame: 48 weeks from enrollment
Population: 12 participants with a week 48 study visit were included in analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acute HIV Infection Treatment Group | Median Change in CD4 Cell Count From Week 0 to Week 48. | 349 cells/mm^3 |
Secondary
Median Time to HIV RNA Suppression to <200 Copies/mL
Time frame: From enrollment to the date of HIV RNA suppression, assessed up to Week 48
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acute HIV Infection Treatment Group | Median Time to HIV RNA Suppression to <200 Copies/mL | 59 days |
Secondary
Minimum Darunavir Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture
Time frame: Week 4 and week 48
Population: Four participants consented to 7 optional lumbar puncture to provide CSF sample for measurement of drug levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Minimum Darunavir Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture | 10 ng/mL |
Secondary
Minimum Darunavir Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure
Time frame: between week 4-12 and between weeks 36-48
Population: Six participants consented to ileal biopsy for measurement of drug levels
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Minimum Darunavir Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure | 987 ng/g |
Secondary
Minimum Darunavir Exposure Range in Semen Among Participants Who Consented to an Optional Collection of Semen
Time frame: Weeks 0-4 and weeks 12, 48
Population: Four participants consented to provide a semen sample for measurement of drug levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Minimum Darunavir Exposure Range in Semen Among Participants Who Consented to an Optional Collection of Semen | 9 ng/mL |
Secondary
Minimum Etravirine Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture
Time frame: Week 4 and week 48
Population: 4 participants consented to 7 optional lumbar puncture to provide CSF sample for measurement of drug levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Minimum Etravirine Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture | 4 ng/mL |
Secondary
Minimum Etravirine Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen
Time frame: Weeks 0-4 and weeks 12, 48
Population: Four participants consented to provide a semen sample for measurement of drug levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Minimum Etravirine Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen | 12 ng/mL |
Secondary
Minimum Etravirine Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure
Time frame: between Week 4-12 and between Weeks 36-48
Population: Six participants consented to ileal biopsy for measurement of drug levels
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Minimum Etravirine Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure | 34 ng/g |
Secondary
Minimum Ritonavir Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen
Time frame: Weeks 0-4 and Weeks 12, 48
Population: Four participants consented to provide a semen sample for measurement of drug levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Minimum Ritonavir Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen | 2 ng/mL |
Secondary
Minimum Ritonavir Exposure Range in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture
Time frame: Week 4 and week 48
Population: Four participants consented to 7 optional lumbar puncture to provide CSF sample for measurement of drug levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Minimum Ritonavir Exposure Range in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture | 2 ng/mL |
Secondary
Minimum Ritonavir Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure
Time frame: between week 4-12 and between weeks 36-48
Population: Six participants consented to ileal biopsy for measurement of drug levels
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Minimum Ritonavir Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure | 96 ng/g |
Secondary
Number of Participants Who Stopped Study Treatment Due to Adverse Event or Intolerance
Time frame: Enrollment to Week 48
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acute HIV Infection Treatment Group | Number of Participants Who Stopped Study Treatment Due to Adverse Event or Intolerance | 1 Participants |
Secondary
Number of Participants With HIV RNA Measurement Above the Limits of Detection in Cerebrospinal Fluid
Time frame: Week 4 and Week 48
Population: Four participants provided 7 CSF samples for measurement of HIV RNA level
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute HIV Infection Treatment Group | Number of Participants With HIV RNA Measurement Above the Limits of Detection in Cerebrospinal Fluid | 0 participants |
Secondary
Number of Participants With Neurocognitive Impairment at Baseline
Time frame: Week 2 or 4
Population: Participants who consented to optional procedure of neurocognitive assessment at baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acute HIV Infection Treatment Group | Number of Participants With Neurocognitive Impairment at Baseline | 8 Participants |
Secondary
Number of Participants With Neurocognitive Impairment at Week 24
Time frame: Week 24
Population: Participants who consented to optional procedure of neurocognitive assessment at week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acute HIV Infection Treatment Group | Number of Participants With Neurocognitive Impairment at Week 24 | 3 Participants |
Secondary
Number of Participants With Neurocognitive Impairment at Week 48
Time frame: Week 48
Population: Participants who consented to optional procedure of neurocognitive assessment at week 48
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acute HIV Infection Treatment Group | Number of Participants With Neurocognitive Impairment at Week 48 | 3 Participants |
Secondary
Number of Participants With Virologic Response
Virologic response to study treatment defined as plasma HIV RNA measurement \<50 copies/mL at week 48
Time frame: 48 weeks from enrollment
Population: All participants retained on study through week 48 were included in the analysis of virologic efficacy at week 48
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acute HIV Infection Treatment Group | Number of Participants With Virologic Response | 9 Participants |
Secondary
Overall Neurocognitive Impairment at Week 24
Neuropsychological performance was assessed at week 2 or 4, week 24 and week 48 in the following measures: Premorbid/language (Wide Range Achievement Test 4 -Reading Subtest), Learning (Hopkins Verbal Learning Test - Revised), Memory (HVLT-R), Speed of Processing (Trailmaking A (Army Individual Test Battery, 1944), 1974, Stroop color, Attention (WAIS-III Symbol Search; Stroop word, Fine motor, Executive (Trailmaking B, Stroop interference, Letter, Category Fluency. An overall summary score of neurocognitive functioning was created by averaging all tests. Participants also completed Patient's Assessment of Own Functioning Inventory (PAOFI) and the Activities of Daily Living Scale (ADLS). Best available demographically corrected normative data were utilized to create z scores. A negative z score denotes below-average performance relative to a US normative comparison population. A higher z score is a better outcome.
Time frame: Week 24
Population: participants who underwent neurocognitive assessment at baseline and week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acute HIV Infection Treatment Group | Overall Neurocognitive Impairment at Week 24 | -0.40 z score | Standard Deviation 0.15 |
Secondary
Overall Neurocognitive Impairment at Week 48
Neuropsychological performance was assessed at baseline (week 2 or 4), week 24 and week 48 in the following domain (measures): Premorbid/language (Wide Range Achievement Test (WRAT) 4 - Reading Subtest), Learning (HVLT-R, Hopkins Verbal Learning Test - Revised), Memory (HVLT-R), Speed of Processing (Trailmaking A (Army Individual Test Battery, 1944), 1974, Stroop color, Attention (WAIS-III Symbol Search; Stroop word, Fine motor, Executive (Trailmaking B, Stroop interference, Letter, Category Fluency. An overall summary score of neurocognitive functioning was created by averaging all tests. Participants also completed the self-reported functional status Patient's Assessment of Own Functioning Inventory (PAOFI) and the Activities of Daily Living Scale (ADLS). Best available demographically corrected normative data were utilized to create z scores. A negative z score denotes below-average performance relative to a US normative comparison population. A higher z score is a better outcome.
Time frame: Week 48
Population: participants who underwent neurocognitive assessment at baseline and week 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acute HIV Infection Treatment Group | Overall Neurocognitive Impairment at Week 48 | -.45 z score | Standard Deviation 0.15 |
Secondary
Overall Neurocognitive Impairment Score at Week 2 or 4
Neuropsychological performance was assessed at Week 2 or 4, Week 24 and Week 48 in the following measures: Premorbid/language (Wide Range Achievement Test 4 -Reading Subtest), Learning (HVLT-R, Hopkins Verbal Learning Test-Revised), Memory (HVLT-R), Speed of Processing (Trailmaking A (Army Individual Test Battery, 1944), 1974, Stroop color, Attention (WAIS-III Symbol Search; Stroop word, Fine motor, Executive (Trailmaking B, Stroop interference, Letter, Category Fluency. An overall summary score was created by averaging all tests. Participants also completed the self-reported functional status Patient's Assessment of Own Functioning Inventory (PAOFI) and the Activities of Daily Living Scale (ADLS). Best available demographically corrected normative data were utilized to create z scores. A negative z score denotes below-average performance relative to a US normative comparison population. A higher z score is a better outcome.
Time frame: Week 2 or 4
Population: participants who underwent neurocognitive assessment at week 2 or 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acute HIV Infection Treatment Group | Overall Neurocognitive Impairment Score at Week 2 or 4 | -0.69 z score | Standard Deviation 0.14 |