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Evaluation of Two Anti-HIV Treatment Strategies in Resource-Limited South African Communities

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ClinicalTrials.gov Identifier: NCT00255840
Recruitment Status : Completed
First Posted : November 21, 2005
Results First Posted : June 16, 2011
Last Update Posted : June 21, 2011
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:
CIPRA SA

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV Infections
Interventions Behavioral: Monitoring by an HIV-trained medical doctor
Behavioral: Monitoring by an HIV-trained primary care nurse
Drug: Efavirenz
Drug: Lamivudine
Drug: Lopinavir/Ritonavir
Drug: Nevirapine
Drug: Stavudine
Enrollment 812
Recruitment Details HIV-positive adult participants were recruited from February 2005 to December 2007 from two primary health care clinics, one in Masiphumelele, Cape Town and the other in Soweto, Johannesburg.
Pre-assignment Details  
Arm/Group Title Antiretroviral Therapy Monitored by Medical Officer Antiretroviral Therapy Managed by Primary Health Care Nurse
Hide Arm/Group Description

First line antiretroviral regimen monitored by a HIV-trained medical doctor:

  1. Stavudine (>60 kg: 40 mg twice daily and <60 kg: 30 mg twice daily)
  2. Lamivudine (150mg twice daily) and
  3. Efavirenz (600mg daily). For women of child bearing potential with a CD4+ count <250 cells/mm3, Nevirapine (200 mg daily x 14 days, then 200 mg twice daily) and for women with a CD4+ count > 250 cells/mm3, Lopinavir/ritonavir (400/100mg twice daily).

First line antiretroviral regimen monitored by HIV-trained primary health care nurse:

  1. Stavudine (>60 kg: 40 mg twice daily and <60 kg: 30 mg twice daily)
  2. Lamivudine (150mg twice daily) and
  3. Efavirenz (600mg daily). For women of child bearing potential with a CD4+ count <250 cells/mm3, Nevirapine (200 mg daily x 14 days, then 200 mg twice daily) and for women with a CD4+ count > 250 cells/mm3, Lopinavir/ritonavir (400/100mg twice daily).
Period Title: Overall Study
Started 408 404
Completed 345 334
Not Completed 63 70
Reason Not Completed
Lost to Follow-up             10             14
Discontinued intervention             53             56
Arm/Group Title Antiretroviral Therapy Monitored by Medical Officer Antiretroviral Therapy Managed by Primary Health Care Nurse Total
Hide Arm/Group Description

First line antiretroviral regimen monitored by a HIV-trained medical doctor:

  1. Stavudine (>60 kg: 40 mg twice daily and <60 kg: 30 mg twice daily)
  2. Lamivudine (150mg twice daily) and
  3. Efavirenz (600mg daily). For women of child bearing potential with a CD4+ count <250 cells/mm3, Nevirapine (200 mg daily x 14 days, then 200 mg twice daily) and for women with a CD4+ count > 250 cells/mm3, Lopinavir/ritonavir (400/100mg twice daily).

First line antiretroviral regimen monitored by HIV-trained primary health care nurse:

  1. Stavudine (>60 kg: 40 mg twice daily and <60 kg: 30 mg twice daily)
  2. Lamivudine (150mg twice daily) and
  3. Efavirenz (600mg daily). For women of child bearing potential with a CD4+ count <250 cells/mm3, Nevirapine (200 mg daily x 14 days, then 200 mg twice daily) and for women with a CD4+ count > 250 cells/mm3, Lopinavir/ritonavir (400/100mg twice daily).
Total of all reporting groups
Overall Number of Baseline Participants 408 404 812
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 408 participants 404 participants 812 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
408
 100.0%
404
 100.0%
812
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 408 participants 404 participants 812 participants
33.2612388  (7.1934154) 32.9739630  (7.3921786) 33.12  (7.29)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 408 participants 404 participants 812 participants
Female
276
  67.6%
297
  73.5%
573
  70.6%
Male
132
  32.4%
107
  26.5%
239
  29.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
South Africa Number Analyzed 408 participants 404 participants 812 participants
408 404 812
1.Primary Outcome
Title Cumulative Treatment Failure Rate of Participants on First Line Antiretroviral Therapy Monitored by Primary Health Care Nurses (Investigative Arm)is Not Inferior to the Cumulative Treatment Failure Rate of Participants Monitored by Doctors (Control Arm).
Hide Description Cumulative treatment failure is a composite endpoint made up of death, virological failure, toxicity failure and protocol-defined loss to follow-up failure.
Time Frame 96 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The primary analysis was an intention-to-treat analysis of any treatment failure with use of Cox proportional hazards regression.
Arm/Group Title Antiretroviral Therapy Monitored by Medical Officer Antiretroviral Therapy Managed by Primary Health Care Nurse
Hide Arm/Group Description:

First line antiretroviral regimen monitored by a HIV-trained medical doctor:

  1. Stavudine (>60 kg: 40 mg twice daily and <60 kg: 30 mg twice daily)
  2. Lamivudine (150mg twice daily) and
  3. Efavirenz (600mg daily). For women of child bearing potential with a CD4+ count <250 cells/mm3, Nevirapine (200 mg daily x 14 days, then 200 mg twice daily) and for women with a CD4+ count > 250 cells/mm3, Lopinavir/ritonavir (400/100mg twice daily).

First line antiretroviral regimen monitored by HIV-trained primary health care nurse:

  1. Stavudine (>60 kg: 40 mg twice daily and <60 kg: 30 mg twice daily)
  2. Lamivudine (150mg twice daily) and
  3. Efavirenz (600mg daily). For women of child bearing potential with a CD4+ count <250 cells/mm3, Nevirapine (200 mg daily x 14 days, then 200 mg twice daily) and for women with a CD4+ count > 250 cells/mm3, Lopinavir/ritonavir (400/100mg twice daily).
Overall Number of Participants Analyzed 408 404
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
44
(39 to 49)
48
(43 to 52)
2.Secondary Outcome
Title To Compare Subject Adherence to First Line Antiretroviral Treatment as Measured by Pill Count, Between the Two Primary Health Care Monitoring Models.
Hide Description [Not Specified]
Time Frame Throughout study
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Drug Resistance HIV Mutations, Defined by Demonstration of Virologic Failure
Hide Description [Not Specified]
Time Frame Throughout the study
Outcome Measure Data Not Reported
4.Secondary Outcome
Title To Compare the Overall Clinical Safety of Antiretroviral Therapy, as Measured by the Occurrence of Clinical and Laboratory Grade 3 and 4 Adverse Events, Between Primary Health Care Monitoring Arms.
Hide Description [Not Specified]
Time Frame Throughout study
Outcome Measure Data Not Reported
5.Secondary Outcome
Title To Estimate the Total and Incremental Costs, From the Provider and Societal Perspectives, of the Two Approaches (the Primary Health Care Sister and Doctor) to the Provision of Antiretrovirals in Primary Health Care Services in Each Study Site.
Hide Description [Not Specified]
Time Frame Throughout study
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Antiretroviral Therapy Monitored by Medical Officer Antiretroviral Therapy Managed by Primary Health Care Nurse
Hide Arm/Group Description

First line antiretroviral regimen monitored by a HIV-trained medical doctor:

  1. Stavudine (>60 kg: 40 mg twice daily and <60 kg: 30 mg twice daily)
  2. Lamivudine (150mg twice daily) and
  3. Efavirenz (600mg daily). For women of child bearing potential with a CD4+ count <250 cells/mm3, Nevirapine (200 mg daily x 14 days, then 200 mg twice daily) and for women with a CD4+ count > 250 cells/mm3, Lopinavir/ritonavir (400/100mg twice daily).

First line antiretroviral regimen monitored by HIV-trained primary health care nurse:

  1. Stavudine (>60 kg: 40 mg twice daily and <60 kg: 30 mg twice daily)
  2. Lamivudine (150mg twice daily) and
  3. Efavirenz (600mg daily). For women of child bearing potential with a CD4+ count <250 cells/mm3, Nevirapine (200 mg daily x 14 days, then 200 mg twice daily) and for women with a CD4+ count > 250 cells/mm3, Lopinavir/ritonavir (400/100mg twice daily).
All-Cause Mortality
Antiretroviral Therapy Monitored by Medical Officer Antiretroviral Therapy Managed by Primary Health Care Nurse
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Antiretroviral Therapy Monitored by Medical Officer Antiretroviral Therapy Managed by Primary Health Care Nurse
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   126/408 (30.88%)      153/404 (37.87%)    
Blood and lymphatic system disorders     
Anemia   2/408 (0.49%)  2 2/404 (0.50%)  4
Leucopenia   0/408 (0.00%)  0 1/404 (0.25%)  1
Neutropenia   2/408 (0.49%)  2 7/404 (1.73%)  7
Pancytopenia   0/408 (0.00%)  0 1/404 (0.25%)  1
Cardiac disorders     
Congestive Heart Failure   1/408 (0.25%)  1 0/404 (0.00%)  0
Eye disorders     
Hyphema   1/408 (0.25%)  1 0/404 (0.00%)  0
Gastrointestinal disorders     
Abdominal Pain   1/408 (0.25%)  1 2/404 (0.50%)  2
Gastritis   1/408 (0.25%)  1 1/404 (0.25%)  1
Gastrointestinal symptoms NOS *  0/408 (0.00%)  0 1/404 (0.25%)  1
Nausea *  0/408 (0.00%)  0 1/404 (0.25%)  1
Pancreatitis   3/408 (0.74%)  3 1/404 (0.25%)  1
Right Upper Quadrant Pain *  1/408 (0.25%)  1 2/404 (0.50%)  2
Umbilical Hernia   0/408 (0.00%)  0 1/404 (0.25%)  1
Vomiting   1/408 (0.25%)  1 1/404 (0.25%)  1
Diarrhea   2/408 (0.49%)  2 0/404 (0.00%)  0
Rectal Bleeding   1/408 (0.25%)  1 0/404 (0.00%)  0
Ruptured Appendix   1/408 (0.25%)  1 0/404 (0.00%)  0
General disorders     
Death *  3/408 (0.74%)  3 1/404 (0.25%)  1
Swelling of Legs   1/408 (0.25%)  1 0/404 (0.00%)  0
Weakness *  1/408 (0.25%)  1 1/404 (0.25%)  1
Adverse Drug Reaction   0/408 (0.00%)  0 1/404 (0.25%)  1
Chest Pain   0/408 (0.00%)  0 1/404 (0.25%)  1
Hepatobiliary disorders     
Cholecystitis   1/408 (0.25%)  1 1/404 (0.25%)  2
Hepatitis   1/408 (0.25%)  1 2/404 (0.50%)  2
Hepatotoxicity   2/408 (0.49%)  2 0/404 (0.00%)  0
Immune system disorders     
Immune Reconstitution Syndrome   1/408 (0.25%)  1 0/404 (0.00%)  0
Infections and infestations     
Abcess   0/408 (0.00%)  0 3/404 (0.74%)  4
Bronchopneumonia   1/408 (0.25%)  1 0/404 (0.00%)  0
Buboes   1/408 (0.25%)  1 0/404 (0.00%)  0
Cerebral Toxoplasmosis   1/408 (0.25%)  1 0/404 (0.00%)  0
Chest Infection   0/408 (0.00%)  0 4/404 (0.99%)  4
Cryptococcal Meningitis   1/408 (0.25%)  1 1/404 (0.25%)  1
Diarrhoea Cryptosporidial   1/408 (0.25%)  1 0/404 (0.00%)  0
Disseminated Tuberculosis   1/408 (0.25%)  1 0/404 (0.00%)  0
Gastroenteritis   3/408 (0.74%)  3 0/404 (0.00%)  0
Hidradenitis Suppurativa   1/408 (0.25%)  1 0/404 (0.00%)  0
Joint Infection   1/408 (0.25%)  1 0/404 (0.00%)  0
Lobar Pneumonia   1/408 (0.25%)  1 0/404 (0.00%)  0
Lower Respiratory Tract Infection   4/408 (0.98%)  4 1/404 (0.25%)  1
Meningitis   1/408 (0.25%)  1 0/404 (0.00%)  0
Pelvic Inflammatory Disease   1/408 (0.25%)  1 0/404 (0.00%)  0
Perineal Abscess   0/408 (0.00%)  0 1/404 (0.25%)  1
Pneumocystis Carnii Pneumonia   1/408 (0.25%)  1 1/404 (0.25%)  1
Pneumonia   6/408 (1.47%)  6 4/404 (0.99%)  4
Pulmonary Tuberculosis   3/408 (0.74%)  3 2/404 (0.50%)  2
Respiratory Tract Infection   4/408 (0.98%)  4 0/404 (0.00%)  0
Tuberculosis Pleurisy   1/408 (0.25%)  1 0/404 (0.00%)  0
Tuberculosis Meningitis   0/408 (0.00%)  0 3/404 (0.74%)  3
Urinary Tract Infection   2/408 (0.49%)  2 0/404 (0.00%)  0
Wound Sepsis   1/408 (0.25%)  1 0/404 (0.00%)  0
Injury, poisoning and procedural complications     
Chemical Poisoning   0/408 (0.00%)  0 1/404 (0.25%)  1
Motor Vehicle Accident   1/408 (0.25%)  1 1/404 (0.25%)  1
Skull Fracture   0/408 (0.00%)  0 1/404 (0.25%)  1
Smoke Inhalation   1/408 (0.25%)  1 0/404 (0.00%)  0
Soft Tissue Injury   2/408 (0.49%)  2 0/404 (0.00%)  0
Stab Wound   1/408 (0.25%)  1 0/404 (0.00%)  0
ALT Increased   7/408 (1.72%)  9 11/404 (2.72%)  12
AST Increased   5/408 (1.23%)  5 10/404 (2.48%)  11
Investigations     
Alkaline Phosphatase Increased   1/408 (0.25%)  1 2/404 (0.50%)  2
GGT Increased   7/408 (1.72%)  8 6/404 (1.49%)  6
Lipase Increased   1/408 (0.25%)  1 2/404 (0.50%)  3
Loss of Weight   1/408 (0.25%)  1 1/404 (0.25%)  1
Lactate Increased   0/408 (0.00%)  0 2/404 (0.50%)  2
Creatinine Increased   0/408 (0.00%)  0 1/404 (0.25%)  1
Metabolism and nutrition disorders     
Dehydration   1/408 (0.25%)  1 1/404 (0.25%)  1
Hyperlactataemia   3/408 (0.74%)  3 17/404 (4.21%)  17
Insulin Dependent Diabetic   0/408 (0.00%)  0 1/404 (0.25%)  1
Lactic acidosis   5/408 (1.23%)  5 9/404 (2.23%)  9
Lipodystrophy   0/408 (0.00%)  0 7/404 (1.73%)  7
Musculoskeletal and connective tissue disorders     
Arthralgia   0/408 (0.00%)  0 1/404 (0.25%)  1
Polyarthritis   1/408 (0.25%)  1 0/404 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lymphoma   1/408 (0.25%)  1 0/404 (0.00%)  0
Karposi's Sarcoma   0/408 (0.00%)  0 1/404 (0.25%)  1
Nervous system disorders     
Cerebrovascular Accident   1/408 (0.25%)  1 2/404 (0.50%)  2
Headache   1/408 (0.25%)  1 1/404 (0.25%)  1
Hemiparesis   0/408 (0.00%)  0 1/404 (0.25%)  1
Left Side Paralysis   0/408 (0.00%)  0 1/404 (0.25%)  1
Mental Retardation   0/408 (0.00%)  0 1/404 (0.25%)  1
Loss of Consciousness   1/408 (0.25%)  1 0/404 (0.00%)  0
Peripheral Neuropathy NOS   0/408 (0.00%)  0 1/404 (0.25%)  1
Pregnancy, puerperium and perinatal conditions     
Antepartum Haemorrhage   1/408 (0.25%)  1 1/404 (0.25%)  1
Abortion Spontaneous   1/408 (0.25%)  1 0/404 (0.00%)  0
Abruptio Plancentae   1/408 (0.25%)  1 0/404 (0.00%)  0
Eclampsia   0/408 (0.00%)  0 1/404 (0.25%)  1
Fetal Death   0/408 (0.00%)  0 1/404 (0.25%)  1
Hellp Syndrome   0/408 (0.00%)  0 1/404 (0.25%)  1
Incomplete Abortion   0/408 (0.00%)  0 1/404 (0.25%)  1
Normal Delivery   0/408 (0.00%)  0 1/404 (0.25%)  1
Stillbirth   0/408 (0.00%)  0 2/404 (0.50%)  2
Psychiatric disorders     
Delirium   1/408 (0.25%)  1 0/404 (0.00%)  0
Parasuicide   1/408 (0.25%)  1 0/404 (0.00%)  0
Renal and urinary disorders     
Acute Renal Failure   0/408 (0.00%)  0 1/404 (0.25%)  1
Reproductive system and breast disorders     
Bartholin's Cyst   0/408 (0.00%)  0 1/404 (0.25%)  1
Vaginal Bleeding   2/408 (0.49%)  2 1/404 (0.25%)  1
Respiratory, thoracic and mediastinal disorders     
Pleural Effusion   0/408 (0.00%)  0 2/404 (0.50%)  2
Pulmonary Oedema   0/408 (0.00%)  0 1/404 (0.25%)  1
Respiratory Distress   0/408 (0.00%)  0 2/404 (0.50%)  2
Asthma   1/408 (0.25%)  1 0/404 (0.00%)  0
Shortness of Breath   1/408 (0.25%)  1 0/404 (0.00%)  0
Skin and subcutaneous tissue disorders     
Bullous Rash   1/408 (0.25%)  1 0/404 (0.00%)  0
Drug Rash   0/408 (0.00%)  0 1/404 (0.25%)  1
Eczema Weeping   1/408 (0.25%)  1 0/404 (0.00%)  0
Seborrheic Dermatitis   1/408 (0.25%)  1 0/404 (0.00%)  0
Stevens Johnson Syndrome   2/408 (0.49%)  2 0/404 (0.00%)  0
Urticaria   0/408 (0.00%)  0 1/404 (0.25%)  1
Social circumstances     
Assault   2/408 (0.49%)  2 1/404 (0.25%)  1
Surgical and medical procedures     
Cholecystectomy   1/408 (0.25%)  1 0/404 (0.00%)  0
Hysterectomy   1/408 (0.25%)  1 0/404 (0.00%)  0
Vascular disorders     
Collapse Cardiovascular   1/408 (0.25%)  1 0/404 (0.00%)  0
Deep Vein Thrombosis   1/408 (0.25%)  1 2/404 (0.50%)  2
Gangrene   0/408 (0.00%)  0 1/404 (0.25%)  1
Hypertension   2/408 (0.49%)  4 1/404 (0.25%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Antiretroviral Therapy Monitored by Medical Officer Antiretroviral Therapy Managed by Primary Health Care Nurse
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   194/408 (47.55%)      119/404 (29.46%)    
Blood and lymphatic system disorders     
Neutropenia   27/408 (6.62%)  34 17/404 (4.21%)  22
Investigations     
GGT increased  [1]  29/408 (7.11%)  36 15/404 (3.71%)  20
Metabolism and nutrition disorders     
Hyperlactatemia   71/408 (17.40%)  79 43/404 (10.64%)  44
Nervous system disorders     
Peripheral Neuropathy   28/408 (6.86%)  29 10/404 (2.48%)  10
Skin and subcutaneous tissue disorders     
Lipodystrophy   39/408 (9.56%)  40 34/404 (8.42%)  35
Indicates events were collected by systematic assessment
[1]
Gamma Glutamyl Transferase
The study design did not address nurse-initiated ART because the prescription of ART in South Africa is restricted to doctors. We noted a high rate of loss to follow-up, but this rate was similar to other resource-constrained settings.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr Ian Sanne
Organization: CIPRA-SA
Phone: +27 11 276 8800
EMail: isanne@witshealth.co.za
Layout table for additonal information
Responsible Party: James McIntyre, CIPRA SA
ClinicalTrials.gov Identifier: NCT00255840     History of Changes
Other Study ID Numbers: CIPRA-SA Project 1
U19AI053217 ( U.S. NIH Grant/Contract )
3U19AI053217-03S1 ( U.S. NIH Grant/Contract )
3U19AI053217-04S1 ( U.S. NIH Grant/Contract )
3U19AI053217-04 ( U.S. NIH Grant/Contract )
First Submitted: November 16, 2005
First Posted: November 21, 2005
Results First Submitted: March 2, 2011
Results First Posted: June 16, 2011
Last Update Posted: June 21, 2011