HIV Infections
Conditions
Keywords
Treatment Naive
Brief summary
HIV infected pregnant women may take single-dose nevirapine (SD NVP) prior to giving birth to prevent mother-to-child transmission (MTCT) of HIV. However, SD NVP may cause NVP resistance in the mother, potentially ruling out some treatment options in the future. The purpose of this study is to determine which of three anti-HIV drug regimens most effectively reduces the development of maternal NVP resistance in HIV infected pregnant women. The effectiveness of short-term (7 day therapy) versus long-term (21-day therapy) regimens will also be compared. The study hypotheses are: 1) intrapartum SD NVP with a 21-day course of antiretroviral therapy (ART) results in less frequent selection of NVP-resistant HIV-1 variants than intrapartum SD NVP with a 7-day course of ART, and 2) a 7- or 21-day course of lamivudine/zidovudine (3TC/ZDV), emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), or lopinavir/ritonavir (LPV/r) following SD NVP will not select nucleoside reverse transcriptase inhibitor (NRTI)- or protease inhibitor (PI)- resistant HIV-1 variants.
Detailed description
A major disadvantage of giving SD NVP is the potential for maternal development of NVP resistance and additional resistance to other nonnucleoside reverse transcriptase inhibitors (NNRTI) in the mother; as a result, future treatment options may be limited for these HIV infected women. The purpose of the study is to determine which of three ART regimens most effectively deters the development of maternal NVP resistance in HIV infected pregnant women postpartum. This study also compared the effectiveness of short-term versus long-term ART in discouraging the development of maternal NVP resistance. Some mothers in this study received ZDV monotherapy prior to SD NVP administration; initiation of ZDV monotherapy was at the discretion of the site investigator and was be provided by this study. Randomization was stratified by receipt of ZDV monotherapy during the pregnancy. Prior to labor, mothers were randomly assigned to receive SD NVP at the onset of labor and one of three postpartum ART regimens: 3TC/ZDV, FTC/TDF, and LPV/r. In addition, participants were randomly assigned to receive 7 or 21 days of their assigned postpartum treatment. Mothers were followed for 96 weeks following delivery; there were 11 study visits for mothers during the study. At the onset of labor, medical and medication history, a targeted physical exam, and an obstetrical exam occurred. Additional physical exams occurred on Day 1 and Weeks 1 and 3. Blood collection occurred at 8 study visits between Weeks 3 and 96. Infants were followed for up to 96 weeks after birth; there were 8 study visits for infants during the study. Infants who had ever been breastfed had study visits at Weeks 16, 24, 48, and 96, and at about 1 and 2 years of age. A physical exam, medication history, and blood collection occurred at each infant visit. Mothers and infants could be prescribed continuing ART, but such ART was be provided by this study.
Interventions
DRUGEmtricitabine/Tenofovir Disoproxil Fumarate
200mg/300mg as one tablet taken orally once daily
DRUGLamivudine/Zidovudine
150mg/300mg as one tablet taken orally twice daily
DRUGLopinavir/Ritonavir
133.3mg/33.3mg as three capsules taken orally twice daily
DRUGsingle dose Nevirapine
one 200 mg tablet taken orally
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for Mothers: * HIV-1 infected * CD4 count 250 cells/mm3 or greater within 30 days of study entry * The following laboratory values obtained within 30 days prior to study entry: absolute neutropil count \>= 750/mm3; hemoglobin \>= 8.0 g/dL; platelet count \>= 50,000/mm3; calculated creatinine clearance (Cockcroft-Gault formula) \> 60 mL/min; AST(SGOT) and ALT(SGPT) \< 5 x ULN; total bilirubin \< 1.5 X ULN. * Pregnant with a viable fetus at 28 to 38 weeks gestation at study entry. * Willing to give birth to baby in a hospital or clinic * Written informed consent from parent or guardian, if applicable
Exclusion criteria
for Mothers: * Any ART, including single-dose NVP, prior to study entry. Mothers who receive ZDV monotherapy prior to labor under the supervision of the site investigator are not excluded. * Known allergy or sensitivity to study drugs or their formulations * Current drug or alcohol abuse that may interfere with the study * Serious illness requiring systemic treatment or hospitalization. Participants who complete therapy or are clinically stable on therapy for at least 14 days prior to study entry are not excluded. * Hepatitis B surface antigen positive within 180 days prior to study entry * Active tuberculosis infection requiring treatment * Prior enrollment in this study * Expect to use ART, except ZDV monotherapy, prior to onset of labor * Expect to use ART other than study medications from delivery to 9 weeks postpartum
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With New Circulating Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)-Resistant Variants as Detected by Standard Composite (Bulk) Genotyping | 2 and 6 weeks after completion of treatment | For the 7-day treatment duration group, only the genotype results from weeks 3 and 7 contributed to the primary endpoint; For the 21-day treatment duration groups, only the genotype results from weeks 5 and 9 contributed to primary endpoint. 10 participants who did not have resistance samples available were excluded from the primary endpoint analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With New PI-resistant Variants as Detected by Standard Composite (Bulk) Genotyping. | 2 and 6 weeks after completion of treatment | For the 7-day treatment duration group, only the genotype results from weeks 3 and 7 contributed; For the 21-day treatment duration groups, only the genotype results from weeks 5 and 9 contributed. |
| Number of Participants With New Circulating NRTI-resistant Variants Detected by Standard Composite (Bulk) Genotyping. | 2 and 6 weeks after completion of treatment | For the 7-day treatment duration group, only the genotype results from weeks 3 and 7 contributed; For the 21-day treatment duration groups, only the genotype results from weeks 5 and 9 contributed. |
| Severe (Grade 3) and Higher Adverse Events and Any Grade Adverse Event That Leads to a Treatment Change From First Day of Study Treatment to Week 12 | From first day of study treatment to week 12 | Grade 3 or higher signs and symptoms, laboratory abnormalities, events that are reported through the EAE system, and any grade event that leads to a treatment change from first day of study treatment to week 12. Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death |
| Number of Participants Who Discontinued Study Treatment Prematurely | From first day of study treatment to last day of study treatment (up to 21 days) | participants assigned to 7-day treatment arm and 21-day treatment arm were supposed to stay in study treatment for 7 days and 21 days respectively. |
Countries
Haiti, India, Malawi, South Africa, Tanzania, Uganda
Participant flow
Recruitment details
Study participants were recruited at 8 sites: 2 from South Africa, 2 from India, and 1 each from Haiti, Uganda, Tanzania, and Malawi, between January 2007 to October 2009.
Pre-assignment details
62 participants who randomized but did not start study treatment were excluded from the analysis. These 62 participants were either off study prior to delivery or delivered on study but did not take any dose of study treatment. All the analyses were restricted to the 422 women who received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| 7-day Lamivudine/Zidovudine (3TC/ZDV) SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV. | 73 |
| 21-day Lamivudine/Zidovudine (3TC/ZDV) SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV. | 68 |
| 7-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF. | 75 |
| 21-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF. | 67 |
| 7-day Lopinavir/Ritonavir (LPV/r) SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r. | 71 |
| 21-day Lopinavir/Ritonavir (LPV/r) SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r | 68 |
| Total | 422 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 3 | 1 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | 7-day Lamivudine/Zidovudine (3TC/ZDV) | 21-day Lamivudine/Zidovudine (3TC/ZDV) | 7-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) | 21-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) | 7-day Lopinavir/Ritonavir (LPV/r) | 21-day Lopinavir/Ritonavir (LPV/r) |
|---|---|---|---|---|---|---|---|
| Actual ZDV exposure during pregnancy no | 155 participants | 27 participants | 21 participants | 28 participants | 25 participants | 28 participants | 26 participants |
| Actual ZDV exposure during pregnancy yes | 267 participants | 46 participants | 47 participants | 47 participants | 42 participants | 43 participants | 42 participants |
| Age, Continuous | 27 years STANDARD_DEVIATION 5 | 27 years STANDARD_DEVIATION 6 | 27 years STANDARD_DEVIATION 5 | 26 years STANDARD_DEVIATION 5 | 26 years STANDARD_DEVIATION 5 | 27 years STANDARD_DEVIATION 6 | 26 years STANDARD_DEVIATION 5 |
| Age, Customized >= 40 years | 7 participants | 2 participants | 1 participants | 1 participants | 0 participants | 2 participants | 1 participants |
| Age, Customized Between 13 and 19 years | 17 participants | 2 participants | 1 participants | 5 participants | 3 participants | 3 participants | 3 participants |
| Age, Customized Between 20 and 29 years | 289 participants | 49 participants | 46 participants | 53 participants | 46 participants | 47 participants | 48 participants |
| Age, Customized Between 30 and 39 years | 109 participants | 20 participants | 20 participants | 16 participants | 18 participants | 19 participants | 16 participants |
| Gestational age at NVP dosing, Continuous | 38 weeks STANDARD_DEVIATION 2 | 38 weeks STANDARD_DEVIATION 2 | 39 weeks STANDARD_DEVIATION 2 | 38 weeks STANDARD_DEVIATION 2 | 38 weeks STANDARD_DEVIATION 3 | 38 weeks STANDARD_DEVIATION 2 | 38 weeks STANDARD_DEVIATION 2 |
| Region of Enrollment Haiti | 58 participants | 12 participants | 11 participants | 10 participants | 7 participants | 9 participants | 9 participants |
| Region of Enrollment India | 104 participants | 15 participants | 18 participants | 20 participants | 19 participants | 16 participants | 16 participants |
| Region of Enrollment Malawi | 85 participants | 13 participants | 14 participants | 14 participants | 12 participants | 17 participants | 15 participants |
| Region of Enrollment South Africa | 60 participants | 13 participants | 8 participants | 10 participants | 9 participants | 10 participants | 10 participants |
| Region of Enrollment Tanzania | 14 participants | 3 participants | 1 participants | 3 participants | 3 participants | 2 participants | 2 participants |
| Region of Enrollment Uganda | 101 participants | 17 participants | 16 participants | 18 participants | 17 participants | 17 participants | 16 participants |
| Screening CD4 count Categorical 250-349 cells/mm^3 | 69 participants | 15 participants | 7 participants | 8 participants | 6 participants | 20 participants | 13 participants |
| Screening CD4 count Categorical 350-499 cells/mm^3 | 150 participants | 24 participants | 21 participants | 29 participants | 29 participants | 25 participants | 22 participants |
| Screening CD4 count Categorical >=500 cells/mm^3 | 203 participants | 34 participants | 40 participants | 38 participants | 32 participants | 26 participants | 33 participants |
| Screening CD4 count Continuous | 545 cells/mm^3 STANDARD_DEVIATION 216 | 538 cells/mm^3 STANDARD_DEVIATION 244 | 585 cells/mm^3 STANDARD_DEVIATION 215 | 537 cells/mm^3 STANDARD_DEVIATION 186 | 545 cells/mm^3 STANDARD_DEVIATION 191 | 505 cells/mm^3 STANDARD_DEVIATION 205 | 566 cells/mm^3 STANDARD_DEVIATION 249 |
| Screening HIV-1 RNA Categorical 100000-749999 copies/mL | 28 participants | 8 participants | 3 participants | 4 participants | 5 participants | 4 participants | 4 participants |
| Screening HIV-1 RNA Categorical 10000-99999 copies/mL | 112 participants | 17 participants | 17 participants | 18 participants | 14 participants | 20 participants | 26 participants |
| Screening HIV-1 RNA Categorical 1000-9999 copies/mL | 148 participants | 17 participants | 26 participants | 33 participants | 25 participants | 29 participants | 18 participants |
| Screening HIV-1 RNA Categorical <=400 copies/mL | 83 participants | 17 participants | 13 participants | 13 participants | 12 participants | 12 participants | 16 participants |
| Screening HIV-1 RNA Categorical 401-999 copies/mL | 48 participants | 12 participants | 8 participants | 7 participants | 11 participants | 6 participants | 4 participants |
| Screening HIV-1 RNA Categorical >=750000 copies/mL | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Screening HIV-1 RNA Categorical Missing/Unknown | 2 participants | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Screening HIV-1 RNA Continuous | 3.56 log10 copies/mL STANDARD_DEVIATION 0.9 | 3.50 log10 copies/mL STANDARD_DEVIATION 1.01 | 3.55 log10 copies/mL STANDARD_DEVIATION 0.9 | 3.54 log10 copies/mL STANDARD_DEVIATION 0.82 | 3.50 log10 copies/mL STANDARD_DEVIATION 0.88 | 3.63 log10 copies/mL STANDARD_DEVIATION 0.9 | 3.66 log10 copies/mL STANDARD_DEVIATION 0.92 |
| Sex: Female, Male Female | 422 Participants | 73 Participants | 68 Participants | 75 Participants | 67 Participants | 71 Participants | 68 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 73 | 0 / 68 | 0 / 75 | 0 / 67 | 0 / 71 | 0 / 68 |
| serious Total, serious adverse events | 2 / 73 | 0 / 68 | 1 / 75 | 0 / 67 | 1 / 71 | 0 / 68 |
Outcome results
Primary
Number of Participants With New Circulating Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)-Resistant Variants as Detected by Standard Composite (Bulk) Genotyping
For the 7-day treatment duration group, only the genotype results from weeks 3 and 7 contributed to the primary endpoint; For the 21-day treatment duration groups, only the genotype results from weeks 5 and 9 contributed to primary endpoint. 10 participants who did not have resistance samples available were excluded from the primary endpoint analysis.
Time frame: 2 and 6 weeks after completion of treatment
Population: 412 women with primary endpoint results available
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 7-day Lamivudine/Zidovudine (3TC/ZDV) | Number of Participants With New Circulating Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)-Resistant Variants as Detected by Standard Composite (Bulk) Genotyping | 1 participants |
| 21-day Lamivudine/Zidovudine (3TC/ZDV) | Number of Participants With New Circulating Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)-Resistant Variants as Detected by Standard Composite (Bulk) Genotyping | 0 participants |
| 7-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) | Number of Participants With New Circulating Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)-Resistant Variants as Detected by Standard Composite (Bulk) Genotyping | 0 participants |
| 21-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) | Number of Participants With New Circulating Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)-Resistant Variants as Detected by Standard Composite (Bulk) Genotyping | 0 participants |
| 7-day Lopinavir/Ritonavir (LPV/r) | Number of Participants With New Circulating Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)-Resistant Variants as Detected by Standard Composite (Bulk) Genotyping | 3 participants |
| 21-day Lopinavir/Ritonavir (LPV/r) | Number of Participants With New Circulating Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)-Resistant Variants as Detected by Standard Composite (Bulk) Genotyping | 1 participants |
Comparison: Compare proportion of women with new NNRTI-resistant variants between treatment durations (7-day vs. 21 day), pooled over ARV regimens (3TC/ZDV, FTC/TDF, and LPV/r), stratified by ARV regimen and the actual receipt of antenatal ZDVp-value: 0.37Cochran-Mantel-Haenszel
Comparison: Compare proportion of women with new NNRTI-resistant variants among ARV regimens (3TC/ZDV vs. FTC/TDF vs. LPV/r), pooled over treatment durations 7-day and 21-day, stratified by treatment duration and the actual receipt of antenatal ZDVp-value: 0.091Cochran-Mantel-Haenszel
Secondary
Number of Participants Who Discontinued Study Treatment Prematurely
participants assigned to 7-day treatment arm and 21-day treatment arm were supposed to stay in study treatment for 7 days and 21 days respectively.
Time frame: From first day of study treatment to last day of study treatment (up to 21 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 7-day Lamivudine/Zidovudine (3TC/ZDV) | Number of Participants Who Discontinued Study Treatment Prematurely | 0 participants |
| 21-day Lamivudine/Zidovudine (3TC/ZDV) | Number of Participants Who Discontinued Study Treatment Prematurely | 2 participants |
| 7-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) | Number of Participants Who Discontinued Study Treatment Prematurely | 0 participants |
| 21-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) | Number of Participants Who Discontinued Study Treatment Prematurely | 0 participants |
| 7-day Lopinavir/Ritonavir (LPV/r) | Number of Participants Who Discontinued Study Treatment Prematurely | 0 participants |
| 21-day Lopinavir/Ritonavir (LPV/r) | Number of Participants Who Discontinued Study Treatment Prematurely | 5 participants |
Secondary
Number of Participants With New Circulating NRTI-resistant Variants Detected by Standard Composite (Bulk) Genotyping.
For the 7-day treatment duration group, only the genotype results from weeks 3 and 7 contributed; For the 21-day treatment duration groups, only the genotype results from weeks 5 and 9 contributed.
Time frame: 2 and 6 weeks after completion of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 7-day Lamivudine/Zidovudine (3TC/ZDV) | Number of Participants With New Circulating NRTI-resistant Variants Detected by Standard Composite (Bulk) Genotyping. | 0 participants |
| 21-day Lamivudine/Zidovudine (3TC/ZDV) | Number of Participants With New Circulating NRTI-resistant Variants Detected by Standard Composite (Bulk) Genotyping. | 1 participants |
| 7-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) | Number of Participants With New Circulating NRTI-resistant Variants Detected by Standard Composite (Bulk) Genotyping. | 1 participants |
| 21-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) | Number of Participants With New Circulating NRTI-resistant Variants Detected by Standard Composite (Bulk) Genotyping. | 1 participants |
| 7-day Lopinavir/Ritonavir (LPV/r) | Number of Participants With New Circulating NRTI-resistant Variants Detected by Standard Composite (Bulk) Genotyping. | 1 participants |
| 21-day Lopinavir/Ritonavir (LPV/r) | Number of Participants With New Circulating NRTI-resistant Variants Detected by Standard Composite (Bulk) Genotyping. | 0 participants |
Secondary
Number of Participants With New PI-resistant Variants as Detected by Standard Composite (Bulk) Genotyping.
For the 7-day treatment duration group, only the genotype results from weeks 3 and 7 contributed; For the 21-day treatment duration groups, only the genotype results from weeks 5 and 9 contributed.
Time frame: 2 and 6 weeks after completion of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 7-day Lamivudine/Zidovudine (3TC/ZDV) | Number of Participants With New PI-resistant Variants as Detected by Standard Composite (Bulk) Genotyping. | 0 participants |
| 21-day Lamivudine/Zidovudine (3TC/ZDV) | Number of Participants With New PI-resistant Variants as Detected by Standard Composite (Bulk) Genotyping. | 0 participants |
| 7-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) | Number of Participants With New PI-resistant Variants as Detected by Standard Composite (Bulk) Genotyping. | 0 participants |
| 21-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) | Number of Participants With New PI-resistant Variants as Detected by Standard Composite (Bulk) Genotyping. | 0 participants |
| 7-day Lopinavir/Ritonavir (LPV/r) | Number of Participants With New PI-resistant Variants as Detected by Standard Composite (Bulk) Genotyping. | 0 participants |
| 21-day Lopinavir/Ritonavir (LPV/r) | Number of Participants With New PI-resistant Variants as Detected by Standard Composite (Bulk) Genotyping. | 0 participants |
Secondary
Severe (Grade 3) and Higher Adverse Events and Any Grade Adverse Event That Leads to a Treatment Change From First Day of Study Treatment to Week 12
Grade 3 or higher signs and symptoms, laboratory abnormalities, events that are reported through the EAE system, and any grade event that leads to a treatment change from first day of study treatment to week 12. Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death
Time frame: From first day of study treatment to week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 7-day Lamivudine/Zidovudine (3TC/ZDV) | Severe (Grade 3) and Higher Adverse Events and Any Grade Adverse Event That Leads to a Treatment Change From First Day of Study Treatment to Week 12 | 5 participants |
| 21-day Lamivudine/Zidovudine (3TC/ZDV) | Severe (Grade 3) and Higher Adverse Events and Any Grade Adverse Event That Leads to a Treatment Change From First Day of Study Treatment to Week 12 | 1 participants |
| 7-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) | Severe (Grade 3) and Higher Adverse Events and Any Grade Adverse Event That Leads to a Treatment Change From First Day of Study Treatment to Week 12 | 1 participants |
| 21-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) | Severe (Grade 3) and Higher Adverse Events and Any Grade Adverse Event That Leads to a Treatment Change From First Day of Study Treatment to Week 12 | 0 participants |
| 7-day Lopinavir/Ritonavir (LPV/r) | Severe (Grade 3) and Higher Adverse Events and Any Grade Adverse Event That Leads to a Treatment Change From First Day of Study Treatment to Week 12 | 2 participants |
| 21-day Lopinavir/Ritonavir (LPV/r) | Severe (Grade 3) and Higher Adverse Events and Any Grade Adverse Event That Leads to a Treatment Change From First Day of Study Treatment to Week 12 | 2 participants |