NNRTI vs PI Regimens for HIV Infected Women After They Have Taken Nevirapine to Prevent Mother-To-Child HIV Transmission (OCTANE)

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00089505
First received: August 5, 2004
Last updated: May 10, 2011
Last verified: May 2011
Results First Received: August 30, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: Emtricitabine
Drug: Emtricitabine/Tenofovir disoproxil fumarate
Drug: Lopinavir/Ritonavir
Drug: Nevirapine
Drug: Tenofovir disoproxil fumarate

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Study participants were recruited at 10 sites from 7 African countries: 3 from South Africa, 2 from Kenya, and 1 each in Botswana, Malawi, Uganda, Zambia and Zimbabwe, between November 2006 to July 2008. The Botswana site enrolled participants from two locations.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
HIV-infected, treatment-naive women, at least 13 years of age with CD4+ count<200 cells/mm^3. Four participants were randomized but did not start treatment.

Reporting Groups
  Description
NVP/NVP For participants had single dose Nevirapine (SD NVP) exposure prior to study entry, Emtricitabine capsules(FTC) 200mg (1 capsule orally), Tenofovir disproxil fumerate (TDF) 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily in the morning for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive Lopinovir/Ritonovir (LPV/RTV)400/100mg (3 capsules orally) twice daily plus two more Nucleoside reverse transcriptase inhibitors (NRTIs). Following the review on 6 October 2008, the Data Safety Monitoring Board(DSMB) recommended release of the results from this arm.
NVP/LPV_r For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP 200mg (1 tablet orally) daily for 14 days before taking it twice daily. plus 2 more NRTIs. Following the review on 6 October 2008, the DSMB recommended release of the results from this arm.
NoNVP/NVP For participants had NO SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally), TDF 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive LPV/RTV 400/100mg (3 capsules orally) twice daily plus two more NRTIs.
NoNVP/LPV_r For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) once daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP daily 200mg (1 tablet orally) for 14 days before taking it twice daily plus 2 more NRTIs.

Participant Flow:   Overall Study
    NVP/NVP     NVP/LPV_r     NoNVP/NVP     NoNVP/LPV_r  
STARTED     121 [1]   120     249 [1]   251  
COMPLETED     112 [2]   118 [3]   228     230  
NOT COMPLETED     9     2     21     21  
Death                 4                 1                 5                 8  
Withdrawal by Subject                 3                 0                 6                 6  
Lost to Follow-up                 1                 1                 9                 7  
Physician Decision                 1                 0                 0                 0  
Protocol Violation                 0                 0                 1                 0  
[1] 2 women never started treatment and per protocol, were not followed and not included in analysis.
[2] The results for NVP/NVP were through database cutoff for DSMB review (by 6 October 2008).
[3] The results for NVP/LPV_r were through database cutoff for DSMB review (by 6 October 2008).



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
NVP/NVP For participants had single dose Nevirapine (SD NVP) exposure prior to study entry, Emtricitabine capsules(FTC) 200mg (1 capsule orally), Tenofovir disproxil fumerate (TDF) 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily in the morning for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive Lopinovir/Ritonovir (LPV/RTV)400/100mg (3 capsules orally) twice daily plus two more Nucleoside reverse transcriptase inhibitors (NRTIs). Following the review on 6 October 2008, the Data Safety Monitoring Board(DSMB) recommended release of the results from this arm.
NVP/LPV_r For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP 200mg (1 tablet orally) daily for 14 days before taking it twice daily. plus 2 more NRTIs. Following the review on 6 October 2008, the DSMB recommended release of the results from this arm.
NoNVP/NVP For participants had NO SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally), TDF 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive LPV/RTV 400/100mg (3 capsules orally) twice daily plus two more NRTIs.
NoNVP/LPV_r For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) once daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP daily 200mg (1 tablet orally) for 14 days before taking it twice daily plus 2 more NRTIs.
Total Total of all reporting groups

Baseline Measures
    NVP/NVP     NVP/LPV_r     NoNVP/NVP     NoNVP/LPV_r     Total  
Number of Participants  
[units: participants]
  121     120     249     251     741  
Age  
[units: years]
Mean ± Standard Deviation
  30  ± 5     31  ± 5     35  ± 7     35  ± 8     33  ± 7  
Age, Customized  
[units: participants]
         
Between 13 and 19 years     0     0     0     2     2  
Between 20 and 29 years     56     49     63     64     232  
Between 30 and 39 years     59     62     125     124     370  
Between 40 and 49 years     5     9     54     49     117  
>=50 years     1     0     7     12     20  
Gender  
[units: participants]
         
Female     121     120     249     251     741  
Male     0     0     0     0     0  
Region of Enrollment  
[units: participants]
         
Kenya     21     23     45     48     137  
Zambia     12     12     19     21     64  
Botswana     13     12     33     30     88  
Uganda     8     9     22     21     60  
Malawi     14     10     22     22     68  
South Africa     35     36     69     67     207  
Zimbabwe     18     18     39     42     117  
CD4 count Categorical  
[units: participants]
         
<50 cells/mm^3     14     11     32     36     93  
Between 50 to 99 cells/mm^3     18     23     63     53     157  
Between 100 to 149 cells/mm^3     35     38     65     78     216  
Between 150 to 199 cells/mm^3     37     32     58     57     184  
Between 200 to 249 cells/mm^3     15     12     18     19     64  
Between 250 to 299 cells/mm^3     1     4     9     4     18  
Between 300 to 349 cells/mm^3     1     0     2     2     5  
>=350 cells/mm^3     0     0     2     2     4  
CD4 count Continuous  
[units: cell/mm^3]
Mean ± Standard Deviation
  136  ± 60     135  ± 61     126  ± 68     125  ± 71     129  ± 67  
Baseline HIV-1 RNA Categorial  
[units: participants]
         
Between 400 and 999 copies/mL     0     1     1     2     4  
Between 1000 and 9,999 copies/mL     5     8     18     11     42  
Between 10,000 and 99,999 copies/mL     44     33     81     88     246  
Between 100,000 and 749,999 copies/mL     61     63     123     128     375  
>=750,000 copies/mL     11     15     26     22     74  
HIV-1 RNA Continuous  
[units: log¬†10¬†copies/mL]
Median ( Inter-Quartile Range )
  5.2  
  ( 4.3 to 5.8 )  
  5.1  
  ( 4.2 to 5.9 )  
  5.2  
  ( 4.2 to 5.9 )  
  5.2  
  ( 4.3 to 5.8 )  
  5.2  
  ( 4.7 to 5.5 )  
WHO stage [1]
[units: participants]
         
Clinical stage I     44     56     97     93     290  
Clinical stage II     42     38     72     67     219  
Clinical stage III     30     25     73     80     208  
Clinical stage IV     5     1     7     11     24  
[1] World Health Organization (WHO) produced WHO Disease Staging System for HIV Infection and Disease in Adults and Adolescents. It is an approach for use in resource limited settings in studies of progression to symptomatic HIV disease. There are 4 stages of disease staging, 1 being the least severe and 4 being the most severe disease stage based on the HIV related symptoms and diagnoses. Please refer to the following web page for detailed staging criteria: http://www.who.int/docstore/hiv/scaling/anex1.html



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time From Randomization to Virologic Failure or Death for Participants Who Had SD NVP Exposure Prior to Study Entry   [ Time Frame: Through database cutoff for DSMB review (by October 6, 2008) with median follow-up 72 weeks and range from 0 to 144 weeks. ]

2.  Primary:   Time From Randomization to Virologic Failure or Death for Participants Without SD NVP Exposure Prior to Study Entry   [ Time Frame: Throughout study with median follow-up 72 weeks and range from 0 to 180 weeks. ]

3.  Secondary:   Number of Participants Who Experienced Virologic Failure or Died.   [ Time Frame: Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP and NVP/LPV_r. Throughout study for NoNVP/NVP and NoNVP/LPV_r. ]

4.  Secondary:   Percent of Participants Who Experienced Virologic Failure or Died   [ Time Frame: Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP and NVP/LPV_r arms. Throughout study for NoNVP/NVP and NoNVP/LPV_r arms. ]

5.  Secondary:   CD4 Count Change From Randomization   [ Time Frame: Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP and NVP/LPV_r. Throughout study for NoNVP/NVP and NoNVP/LPV_r. Week 48 and 96. ]

6.  Secondary:   Number of Participants Who Experienced Treatment-related Toxicity That Led to Discontinuation of Randomized Regimen.   [ Time Frame: Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP and NVP/LPV_r. Throughout study for NoNVP/NVP and NoNVP/LPV_r. ]

7.  Secondary:   Number of Participants Who Experienced HIV-related Disease Progression or Death   [ Time Frame: Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP and NVP/LPV_r. Throughout study for NoNVP/NVP and NoNVP/LPV_r. ]

8.  Secondary:   Number of Participants Who Received NVP-containing Regimens at Randomization and Experienced NVP-associated Rash or Grade 2+ Liver Lab Abnormality   [ Time Frame: Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP arm. Throughout study for NoNVP/NVP arm. ]

9.  Secondary:   Percent of Participants Who Reported to Never Missed Any of the Study Drug Regimen in the Past Month   [ Time Frame: Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP and NVP/LPV_r arms. Throughout study for NoNVP/NVP and NoNVP/LPV_r arms. ]


  Serious Adverse Events


  Other Adverse Events
  Hide Other Adverse Events

Time Frame Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP and NVP/LPV_r arms (with median follow-up: 72 weeks; range 0 -144 weeks). Throughout study for NoNVP/NVP and NoNVP/LPV_r arms (median follow-up: 72 weeks; range 0-180 weeks).
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
NVP/NVP For participants had single dose Nevirapine (SD NVP) exposure prior to study entry, Emtricitabine capsules(FTC) 200mg (1 capsule orally), Tenofovir disproxil fumerate (TDF) 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily in the morning for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive Lopinovir/Ritonovir (LPV/RTV)400/100mg (3 capsules orally) twice daily plus two more Nucleoside reverse transcriptase inhibitors (NRTIs). Following the review on 6 October 2008, the Data Safety Monitoring Board(DSMB) recommended release of the results from this arm.
NVP/LPV_r For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP 200mg (1 tablet orally) daily for 14 days before taking it twice daily. plus 2 more NRTIs. Following the review on 6 October 2008, the DSMB recommended release of the results from this arm.
NoNVP/NVP For participants had NO SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally), TDF 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive LPV/RTV 400/100mg (3 capsules orally) twice daily plus two more NRTIs.
NoNVP/LPV_r For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) once daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP daily 200mg (1 tablet orally) for 14 days before taking it twice daily plus 2 more NRTIs.

Other Adverse Events
    NVP/NVP     NVP/LPV_r     NoNVP/NVP     NoNVP/LPV_r  
Total, other (not including serious) adverse events          
# participants affected / at risk     110/121     105/120     225/249     227/251  
Blood and lymphatic system disorders          
Lymphadenopathy † 1        
# participants affected / at risk     4/121 (3.31%)     9/120 (7.50%)     17/249 (6.83%)     12/251 (4.78%)  
Gastrointestinal disorders          
Abdominal pain † 1        
# participants affected / at risk     14/121 (11.57%)     12/120 (10.00%)     22/249 (8.84%)     26/251 (10.36%)  
Abdominal pain lower † 1        
# participants affected / at risk     3/121 (2.48%)     8/120 (6.67%)     14/249 (5.62%)     18/251 (7.17%)  
Diarrhoea † 1        
# participants affected / at risk     15/121 (12.40%)     17/120 (14.17%)     29/249 (11.65%)     38/251 (15.14%)  
Nausea † 1        
# participants affected / at risk     10/121 (8.26%)     3/120 (2.50%)     19/249 (7.63%)     23/251 (9.16%)  
Vomiting † 1        
# participants affected / at risk     17/121 (14.05%)     14/120 (11.67%)     33/249 (13.25%)     32/251 (12.75%)  
General disorders          
Asthenia † 1        
# participants affected / at risk     6/121 (4.96%)     2/120 (1.67%)     7/249 (2.81%)     14/251 (5.58%)  
Chest pain † 1        
# participants affected / at risk     9/121 (7.44%)     5/120 (4.17%)     30/249 (12.05%)     25/251 (9.96%)  
Chills † 1        
# participants affected / at risk     12/121 (9.92%)     12/120 (10.00%)     14/249 (5.62%)     20/251 (7.97%)  
Malaise † 1        
# participants affected / at risk     6/121 (4.96%)     6/120 (5.00%)     10/249 (4.02%)     9/251 (3.59%)  
Pain † 1        
# participants affected / at risk     7/121 (5.79%)     8/120 (6.67%)     14/249 (5.62%)     11/251 (4.38%)  
# events                 251  
Pyrexia † 1        
# participants affected / at risk     22/121 (18.18%)     17/120 (14.17%)     52/249 (20.88%)     46/251 (18.33%)  
Infections and infestations          
Body tinea † 1        
# participants affected / at risk     7/121 (5.79%)     3/120 (2.50%)     10/249 (4.02%)     9/251 (3.59%)  
Gastroenteritis † 1        
# participants affected / at risk     7/121 (5.79%)     4/120 (3.33%)     13/249 (5.22%)     15/251 (5.98%)  
Genital herpes † 1        
# participants affected / at risk     7/121 (5.79%)     5/120 (4.17%)     8/249 (3.21%)     6/251 (2.39%)  
Herpes zoster † 1        
# participants affected / at risk     3/121 (2.48%)     2/120 (1.67%)     13/249 (5.22%)     8/251 (3.19%)  
Malaria † 1        
# participants affected / at risk     21/121 (17.36%)     25/120 (20.83%)     43/249 (17.27%)     43/251 (17.13%)  
Oral candidiasis † 1        
# participants affected / at risk     6/121 (4.96%)     3/120 (2.50%)     13/249 (5.22%)     15/251 (5.98%)  
# events                 251  
Pelvic inflammatory disease † 1        
# participants affected / at risk     4/121 (3.31%)     6/120 (5.00%)     12/249 (4.82%)     15/251 (5.98%)  
Pneumonia bacterial † 1        
# participants affected / at risk     9/121 (7.44%)     4/120 (3.33%)     21/249 (8.43%)     22/251 (8.76%)  
Pulmonary tuberculosis † 1        
# participants affected / at risk     5/121 (4.13%)     5/120 (4.17%)     9/249 (3.61%)     15/251 (5.98%)  
Upper respiratory tract infection † 1        
# participants affected / at risk     18/121 (14.88%)     15/120 (12.50%)     33/249 (13.25%)     31/251 (12.35%)  
Urinary tract infection † 1        
# participants affected / at risk     5/121 (4.13%)     6/120 (5.00%)     13/249 (5.22%)     16/251 (6.37%)  
Vulvovaginal cadidiasis † 1        
# participants affected / at risk     13/121 (10.74%)     15/120 (12.50%)     26/249 (10.44%)     32/251 (12.75%)  
Investigations          
Alanine aminotransferase increased † 1        
# participants affected / at risk     23/121 (19.01%)     10/120 (8.33%)     40/249 (16.06%)     20/251 (7.97%)  
Aspartate aminotransferase increased † 1        
# participants affected / at risk     23/121 (19.01%)     12/120 (10.00%)     49/249 (19.68%)     31/251 (12.35%)  
Blookd albumin abnormal † 1        
# participants affected / at risk     17/121 (14.05%)     15/120 (12.50%)     38/249 (15.26%)     36/251 (14.34%)  
Blood alkaline phosphatase increased † 1        
# participants affected / at risk     8/121 (6.61%)     1/120 (0.83%)     20/249 (8.03%)     2/251 (0.80%)  
Blood bicarbonate abnormal † 1        
# participants affected / at risk     12/121 (9.92%)     8/120 (6.67%)     26/249 (10.44%)     25/251 (9.96%)  
Blood cholesterol abnormal † 1        
# participants affected / at risk     1/121 (0.83%)     3/120 (2.50%)     14/249 (5.62%)     14/251 (5.58%)  
Blood glucose decreased † 1        
# participants affected / at risk     7/121 (5.79%)     4/120 (3.33%)     10/249 (4.02%)     4/251 (1.59%)  
Blood potassium decreased † 1        
# participants affected / at risk     17/121 (14.05%)     8/120 (6.67%)     6/249 (2.41%)     21/251 (8.37%)  
Blood sodium decreased † 1        
# participants affected / at risk     21/121 (17.36%)     24/120 (20.00%)     49/249 (19.68%)     58/251 (23.11%)  
Haemoglobin decreased † 1        
# participants affected / at risk     14/121 (11.57%)     12/120 (10.00%)     38/249 (15.26%)     40/251 (15.94%)  
Low density lipoprotein † 1        
# participants affected / at risk     3/121 (2.48%)     5/120 (4.17%)     14/249 (5.62%)     9/251 (3.59%)  
Neutrophil count decreased † 1        
# participants affected / at risk     28/121 (23.14%)     35/120 (29.17%)     68/249 (27.31%)     64/251 (25.50%)  
Weight decreased † 1        
# participants affected / at risk     7/121 (5.79%)     10/120 (8.33%)     10/249 (4.02%)     25/251 (9.96%)  
White blood cell count decreased † 1        
# participants affected / at risk     11/121 (9.09%)     14/120 (11.67%)     21/249 (8.43%)     33/251 (13.15%)  
Metabolism and nutrition disorders          
Decreased appetite † 1        
# participants affected / at risk     4/121 (3.31%)     6/120 (5.00%)     13/249 (5.22%)     21/251 (8.37%)  
Musculoskeletal and connective tissue disorders          
Arthralgia † 1        
# participants affected / at risk     8/121 (6.61%)     10/120 (8.33%)     15/249 (6.02%)     21/251 (8.37%)  
Back pain † 1        
# participants affected / at risk     6/121 (4.96%)     5/120 (4.17%)     11/249 (4.42%)     14/251 (5.58%)  
# events             249      
Nervous system disorders          
Headache † 1        
# participants affected / at risk     25/121 (20.66%)     31/120 (25.83%)     53/249 (21.29%)     51/251 (20.32%)  
Pregnancy, puerperium and perinatal conditions          
Pregnancy † 1        
# participants affected / at risk     3/121 (2.48%)     6/120 (5.00%)     19/249 (7.63%)     24/251 (9.56%)  
Renal and urinary disorders          
Dysuria † 1        
# participants affected / at risk     6/121 (4.96%)     7/120 (5.83%)     12/249 (4.82%)     11/251 (4.38%)  
Reproductive system and breast disorders          
Vaginal discharge † 1        
# participants affected / at risk     17/121 (14.05%)     14/120 (11.67%)     45/249 (18.07%)     42/251 (16.73%)  
Vulvovaginal pruritus † 1        
# participants affected / at risk     10/121 (8.26%)     11/120 (9.17%)     19/249 (7.63%)     18/251 (7.17%)  
Respiratory, thoracic and mediastinal disorders          
Cough † 1        
# participants affected / at risk     28/121 (23.14%)     26/120 (21.67%)     60/249 (24.10%)     55/251 (21.91%)  
Dyspnoea † 1        
# participants affected / at risk     5/121 (4.13%)     5/120 (4.17%)     10/249 (4.02%)     15/251 (5.98%)  
Oropharyngeal pain † 1        
# participants affected / at risk     11/121 (9.09%)     3/120 (2.50%)     15/249 (6.02%)     13/251 (5.18%)  
Skin and subcutaneous tissue disorders          
Pruritus † 1        
# participants affected / at risk     16/121 (13.22%)     14/120 (11.67%)     31/249 (12.45%)     34/251 (13.55%)  
Rash † 1        
# participants affected / at risk     28/121 (23.14%)     27/120 (22.50%)     66/249 (26.51%)     67/251 (26.69%)  
Rash papular † 1        
# participants affected / at risk     7/121 (5.79%)     6/120 (5.00%)     20/249 (8.03%)     17/251 (6.77%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 10.0



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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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