Background
Methods
Eligibility criteria
Search methods for identification of studies
Database | Terms |
---|---|
PubMed/Medline | 1. Randomized controlled trial.pt. |
2. Controlled clinical trial.pt. | |
3. Randomized.ab. | |
4. Placebo.ab. | |
5. Drugtherapy.fs. | |
6. Randomly.ab. | |
7. Trial.ab. | |
8. Groups.ab. | |
9. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 | |
10. Exp animals/not humans.sh. | |
11. 9 not 10 | |
12. (cluster$ adj6 randomi$).mp. | |
13. ((communit$ adj6 intervention$) or (communit$ adj6 randomi$)).mp. | |
14. group$ randomi$.mp. | |
15. cluster-randomi$.mp. | |
16. 12 or 13 or 14 or 15 | |
17. 11 or 16 | |
18. ((direct$ adj6 observ$) or (treat$ adj6 partner$) or (treat$ adj6 support$) or (patient$ adj6 support$) or (patient$ adj6 select$) or (peer adj6 health$) or (peer$ adj6 deliver$)).mp. | |
19. (Home based care or (facilit$ adj6 base$)).mp. | |
20. 18 or 19 | |
21. Exp antiretroviral therapy, highly active/ | |
22. Hiv treatment.mp. | |
23. Hiv care.mp. | |
24. 21 or 22 or 23 | |
25. ((viral load) or (HIV viral load) or (virologic$ adj6 fail$) or (virologic$ adj6 outcome$) or (treat$ adj6 fail$) or (treat$ adj6 success$)).mp. | |
26. 24 or 25 | |
27. 20 and 26 | |
28. 17 and 27 | |
29. Exp africa/ | |
30. 28 and 29 | |
EMBASE | 1. Double-blind:.mp. or placebo.tw. or blind:.tw. |
2. (Cluster: adj6 randomi:).mp. | |
3. ((communit: adj6 intervention:) or (communit: adj6 randomi:)).mp. | |
4. Group: randomi:.mp. | |
5. Cluster-randomi:.mp. | |
6. 2 or 3 or 4 or 5 | |
7. 1 or 6 | |
8. ((direct: adj6 observ:) or (treat: adj6 partner:) or (treat: adj6 support:) or (patient: adj6 support:) or (patient: adj6 select:) or (peer adj6 health:) or (peer: adj6 deliver:)).mp. | |
9. (Home based care or (facility: adj6 base:)).mp. | |
10. 8 or 9 | |
11. Exp antiretroviral therapy, highly active/ | |
12. Hiv treatment.mp. | |
13. Hiv care.mp. | |
14. 11 or 12 or 13 | |
15. ((viral load) or (HIV viral load) or (virologic: adj6 fail:) or (virologic: adj6 outcome:) or (treat: adj6 fail:) or (treat: adj6 success:)).mp. | |
16. 14 or 15 | |
17. 10 and 16 | |
18. 7 and 17 | |
19. exp africa/ | |
20. 18 and 19 |
Data collection and analysis
Selection of studies
Data extraction and management
Assessment of risk of bias in included studies
Measures of treatment effect and unit of analysis
Assessment of heterogeneity
Assessment of reporting biases
Data synthesis
Sensitivity analyses
Results
Description of studies
Characteristics of included studies
Study | Design | Study duration | Setting | Inclusion and exclusion criteria | Age | Gender | Sample size analysed | Intervention | Interval to viral load measure | HIV viral load outcomes |
---|---|---|---|---|---|---|---|---|---|---|
Jaffar et al. [37] | Cluster randomised trial: Equivalence trial
| 36 months | Home and Outpatient clinics in Jinja district, Uganda |
Included: 1. Patients >18 years old; 2. Starting ART for the first time. Excluded: Patients living 100 km away from the ART clinic, where the provision of the home-based intervention was not possible. | Mean age in intervention arm 37 years (range 32–44); Mean age in control arm 38 years (range 33–44) | 73% Female (625/859) in intervention arm; 68% Female (406/594) in control arm |
n = 1212: 729 (22 clusters) in intervention arm; 483 (22 clusters) in control arm |
Intervention arm: monthly visits to a patient’s home by field staff to deliver ARVs and monitor signs and symptoms of drug toxicity or disease progression, and provide adherence support. Control arm: Standard care provided at the clinic. | Viral load measured at 6, 12, 18, 24,30 and 36 months |
Time to RNA viral load >500 copies/ml. “Home-based HIV care was as effective as was facility-based care.”% of persons with undetectable viral load at 12 months in intervention arm = (729–117)/729 = 84.0%;% of persons with undetectable viral load at 12 months in control arm: (483–80)/483 = 83.4%. Rate ratio 1 · 04 (95% CI: 0 · 78 – 1 · 40; equivalence shown). Odds Ratio = 1.04 (95% CI: 0.78 – 1.40)
§
|
Nachega et al. [35] | Randomised controlled trial: Superiority trial
| 24 months | Home and Public clinic in Cape Town, South Africa |
Included: 1. Male or non-pregnant female ≥18 years old; 2. HIV infection documented by two serologic tests; 3. Eligible to start ART (CD4 ≤ 200 cells/μL or WHO Clinical Stage IV disease); 4. Living in the study site catchment area at a stable address; 5. Willing to disclose HIV status to a treatment supporter; 6. Signed informed consent. Excluded: 1. Patients with prior ART use; 2. Life expectancy <6 months; 3. Karnofsky Performance Score <60; 4. Serious liver disease; or 5. History of single dose nevirapine for prevention of mother to child transmission of HIV infection. | Mean age in intervention arm 35.7 years (SD 9.7); Mean age in control arm 36.7 years (SD 9.2) | 57.7% female in intervention arm; 57.7% female in control arm |
n = 272: 136 in intervention arm; 136 in control arm |
Intervention arm: In addition to standard care at the clinic, trained treatment supporters provided ART adherence support, observed at least one medication dose daily and documented it on a study adherence chart. Control arm: Standard care provided at the clinic. | Viral load measured at 12 and 24 months |
RNA viral load <400 copies/ml. “DOT-ART showed no effect on virologic outcomes”.% of persons with undetectable viral load at 12 months in intervention arm = 99/(99 + 37) = 72.8%;% of persons with undetectable viral load at 12 months in control arm = 93/(93 + 43) = 68.4%. Odds Ratio of HIV suppression at 12 months = (99/37)/ (93/43) = 1.24 (95% CI: 0.73 – 2.09)
|
Chang et al. [38] | Cluster randomised trial: Superiority trial
| 48 months | Home and Public clinics in rural Rakai District, South West Uganda |
Included: All adult patients who were either already on ART at the start of the trial or were started on ART at any time during the trial. | Mean age in intervention arm 35.5 years (range 15–76); Mean age in control arm 34.0 years (range 17–70) | 65.8% female in intervention arm; 67.5% female in control arm |
n = 620: 456 (10 clusters) in intervention arm; 164 (5 clusters) in control arm |
Intervention arm: Standard care of ARV delivery at the clinic plus biweekly home-based review by a peer health worker who checked for symptoms of treatment failure; patient self-report of adherence; pill count and provision of counselling and education in ART adherence and general HIV/AIDS-related issues. Control arm: Standard ART care provided at the clinic. | Viral load measured at 6, 12, 18, 24,30, 36, 42, 48 months |
RNA viral load >400 copies/ml. At 12 months (48 weeks), no significant differences were found between the intervention and control arm.% of persons with undetectable viral load at 12 months in intervention arm = (456–42)/456 = 90.8%;% of persons with undetectable viral load at 12 months in control arm = (164–18)/164 = 89.0%. Risk Ratio 0.83 (95% CI: 0.47 – 1.48). Odds Ratio of HIV suppression at 12 months = 1/0.83 = 1.20 (95% CI: 0.68 – 2.13)
|
Taiwo et al. [36] | Randomised controlled trial: Superiority trial
| 12 months | Home and Tertiary Hospital HIV clinic in Jos, Nigeria |
Included: 1. HIV-1-infected; 2. Treatment-naïve; 3. Age >15 years; 4. Eligible for ART (clinical diagnosis of AIDS, CD4 count <350 cells/μL with HIV-related symptoms or CD4 count <200 cells/μL regardless of symptoms); 5.Willingness and ability to select a treatment partner. Excluded: Patients with severe illness. | Mean age 34.2 years (SD 8.9) | 66.1% female in intervention arm; 63.3% in control arm |
n = 499: 248 in the intervention arm; 251 in the control arm |
Intervention arm: In addition to standard care at the clinic, a treatment partner residing in same house or close proximity observed the ingestion of ARVs at least once daily. The treatment partner reported adverse effects and reminded participants of drug pick-up at the hospital. Control arm: Standard care provided at the Hospital HIV clinic. | Viral load measured at 6 and 12 months |
RNA viral load <400 copies/ml. At 12 months (48 weeks), no significant differences were found in HIV suppression between the intervention and control arm. % of persons with undetectable viral load at 12 months in intervention arm = 162/248 = 65.3%;% of persons with undetectable viral load at 12 months in control arm = 149/251 = 59.4%. Odds Ratio = 1.28 (95% CI: 0.89 – 1.84)
|
Matovu et al. [17] | Randomised controlled trial: Non-inferiority trial
| 12 months | Home and PMTCT follow-up clinic, Mulago National Referral Hospital in Kampala, Uganda |
Included: 1. Female; 2. Age ≥18 years; 3. Provision of written informed consent; 4. ≥36 weeks of gestation; 5. Eligible for ART (WHO Clinical Stage II/IV or CD4 counts <200 cells/μL); 6. Demonstrated compliance with ART screening visits; 7. Residence in a stable home within 15 km of Mulago Hospital; 8. Willing and able to come to the clinic regularly without transport reimbursement; 9. Willing to be home visited. | Mean age in intervention arm 27.8 years (SD 4.9); Mean age in control arm 27.0 years (SD 5.4) | All Females |
n = 85: 45 in the intervention arm; 40 in the control arm |
Intervention arm: Involved peer counsellors and home visiting, combined with nurses providing care at routine visits, and longer intervals between scheduled visits. Control arm: Standard care provided at the Hospital promoted adherence through routine counselling at each scheduled visit, care provided by a medical officer at each visit, and shorter intervals between visits. | Viral load measured at 6 and 12 months |
RNA viral load <400 copies/ml.% of persons with undetectable viral load at 12 months was similar in the intervention (= 88%) and control (= 91%) arm. Odds Ratio of HIV suppression at 12 months = (0.88/ (1–0.88)) / (0.91/ (1–0.91)) = 0.73 (95% CI: 0.18 – 2.96)
|
Risk of bias in included studies
Study | Adequate sequence generated? | Allocation concealment? | Blinding of participants and personnel? | Blinding of viral load assessment? | Incomplete outcome data addressed? (Missing at follow up = treatment failure) | Free of other bias? |
---|---|---|---|---|---|---|
Jaffar et al. [37] | Yes. | Yes. | No. | Yes. | No. | Yes. |
Cards were sealed in advance and labelled with stratum numbers and placed into a box | Sealed cards were drawn from a concealed box. | The study was cluster randomized trial; researchers and participants knew which clusters were receiving the interventions. | Probably done, because Blood taken for viral load testing was for research purposes; the testing was done in batches rather than in real-time. | “Those who withdrew or were lost to follow-up before 12 months were excluded from the primary endpoint analysis…” | The two groups were well balanced according to baseline characteristics apart from CD4-cell count, which was lower in the home-based than in the facility-based group [39]. There were no losses of clusters. The analysis adjusted for the effect clustering | |
Nachega et al. [35] | Yes. | Yes. | No. | Unclear. | Yes. | No. |
Probably done, because there was sequential allocation concealment | “[T]reatment assignments were placed in opaque envelopes, which were sequentially opened by the study coordinator at enrolment.” | The study was an open-label, randomized controlled trial; both the researchers and the participants knew which intervention was being administered. | Measurement of viral loads performed was every 6 months as part of routine monitoring | Missing viral load values were considered detectable. | Trial terminated early for futility by an independent Data and Safety Monitoring Board | |
Chang et al. [38] | Yes. | Yes. | No. | Unclear. | No. | No. |
An allocation sequence was generated | Random allocation was by drawing of lots. | The study was cluster randomized trial; researchers and participants knew which clusters were receiving the interventions. | "Viral loads … were performed every 24 weeks on all patients as part of routine patient monitoring procedures." | Those who died or were lost to follow-up were excluded from the analysis of shorter-term virologic outcomes | Contamination in the control arm was reported in subsequent evaluation study [40]. | |
Taiwo et al. [36] | Yes. | Yes. | Yes. | No. | Yes. | Yes. |
“Using a computer-generated allocation sequence, randomization was performed …” | Probably done, because there was computer-generated allocation sequence. | “The study pharmacist, who was blinded to treatment arm, provided one-on-one reinforcement of the education provided by the adherence counsellor plus information specific to each participant’s regimen.” | Probably not done because patients who had detectable viral loads at week 24 underwent intensive adherence retraining with the adherence counsellor. | “[P]articipants who were missing virologic indicators and were reported to have died were counted as failures.” | There were no significant differences between treatment groups at baseline. | |
Matovu et al. [17] | Yes. | Unclear. | No. | Unclear. | No. | No. |
Probably done, because patients were randomly allocated. | Insufficient information to permit judgement of “Yes” or “No”. | The study was an open randomized non-inferiority intervention trial. | Insufficient information to permit judgement of “Yes” or “No”. | Patients lost to follow-up were excluded from the analysis. | Baseline viral load was adjusted for. This means there were significant differences in viral loads between intervention groups at baseline. |