Adherence-Enhancing Interventions for HIV Patients on ART
Adherence-Enhancing Interventions for HIV Patients on ART
The systematic literature search was performed in the following databases: EMBASE (via EMBASE, including MEDLINE records), CENTRAL (via the Cochrane Library) and PsycInfo (via EBSCO). A basic search strategy was developed and adapted for each database provider. The search strategy combined various synonyms, antonyms, acronyms and medical subject headings related to adherence, HIV and HAART. Furthermore, a modified version of the Cochrane search filter to identify RCTs was included (the full search strategies are available in Appendix 1). The search was limited to a publication date after January 2001 (for an explanation of search period limitation, see inclusion criteria) and was conducted on 25 May 2012.
The inclusion criteria for the review were as follows.
Different dosages and application types were excluded because they have different pharmacodynamics and pharmacokinetics, which could be associated with adverse events that might have an impact on adherence. The patient recruitment period (criterion 7) was restricted because the first protease inhibitor (lopinavir/Kaletra®, AbbVie Inc., North Chicago, Illinois, USA) was approved by the U.S. Food and Drug Administration in September 2000 and the European Medical Association in April 2001. This was the beginning of a new era for HAART regimes, and it involved a change in clinical outcomes as well as intake regimes, side effects and, consequently, adherence. Adherence is difficult to measure, and several definitions of adherence were used, making it difficult to compare different interventions only on the basis of adherence rates. Furthermore, adherence has no direct patient benefit. Therefore, it is necessary to focus on clinical outcomes when comparing interventions (criterion 4). Clinical endpoints were chosen because it was not expected that patient-relevant outcomes (e.g. AIDS, death and quality of life) would be analysed in the trials and, moreover, viral load and CD4 cell count are validated surrogates. As adherence interventions are specific in their settings and patient profiles, a comparison between developed and less/least developed countries did not seem reasonable. Thus, RCTs conducted exclusively in regions of WHO mortality stratum A were considered.
Titles and abstracts were screened by two reviewers independently according to a priori defined inclusion criteria. The full texts of potentially eligible articles were then obtained. Two reviewers assessed the eligibility of the full texts according to the review inclusion criteria. Differences between reviewers were discussed until a consensus was reached. The references of the included publications were checked for further potentially relevant publications. If the fulfilment of the inclusion criteria could not be assessed because of a lack of information in the publication, the corresponding authors were contacted. If the authors did not reply within 4 weeks, the respective inclusion criterion was considered as not fulfilled, and the trial was excluded.
The data were extracted in standardized tables. Information on the region and setting of the trial, special inclusion criteria regarding gender and mental disorders, patient characteristics (see Appendix 3), intervention(s) and control, the duration of intervention and follow-up, the definition and measurement of adherence and the results were summarized in these tables. Gender and mental disorders were extracted because both were expected to have a strong influence on adherence. If outcomes were measured at multiple time-points, only the last assessment of the intervention and follow-up period was extracted. For different measures of the same clinical outcome (e.g. undetectable viral load and mean viral load), the measure assessed at baseline and follow-up was presented. The results were considered statistically significant if the P-value was < 0.05 or the authors declared the results in their publication to be statistically significant without stating a level of significance. In the latter case, a note was made. All data were extracted by one reviewer and checked by a second for quality assurance.
The Cochrane risk of bias tool was used for methodological quality assessment of the included trials.
Because of the obvious nature of adherence-enhancing interventions, the blinding of patients and personnel was not applicable. The respective quality criteria were therefore unnecessary and not assessed. Therefore, the following six evaluation criteria were used to assess the risk of bias.
The criteria were rated as 'fulfilled', 'not fulfilled' or 'not applicable'. The original Cochrane risk of bias tool also allows the category of 'unclear'. In the assessment presented here, the category 'unclear' was judged as 'not fulfilled'. The quality assessment was performed by two reviewers independently, and discrepancies were resolved in a discussion or by involving an unbiased third person.
High heterogeneity was expected as a consequence of the diversity of existing adherence-enhancing interventions and different target populations. Therefore, a quantitative data synthesis using a meta-analysis was not conducted.
There was no study protocol for this review.
Methods
The systematic literature search was performed in the following databases: EMBASE (via EMBASE, including MEDLINE records), CENTRAL (via the Cochrane Library) and PsycInfo (via EBSCO). A basic search strategy was developed and adapted for each database provider. The search strategy combined various synonyms, antonyms, acronyms and medical subject headings related to adherence, HIV and HAART. Furthermore, a modified version of the Cochrane search filter to identify RCTs was included (the full search strategies are available in Appendix 1). The search was limited to a publication date after January 2001 (for an explanation of search period limitation, see inclusion criteria) and was conducted on 25 May 2012.
The inclusion criteria for the review were as follows.
Patients: adult (at least 80% of trial population at least 18 years of age) patients with an HIV infection currently treated with HAART.
Intervention/comparison: interventions including any type of adherence-enhancing component (no different dosages or different types of application of the same substance; intake without the presence of a health care professional).
Primary outcome: adherence.
Secondary outcomes: clinical parameters (CD4 cell count or viral load as an outcome).
Study type: RCT or cluster RCT.
Language: article in English or German.
Patient enrolment: after 2001.
Region: trial conducted in WHO mortality stratum A.
Different dosages and application types were excluded because they have different pharmacodynamics and pharmacokinetics, which could be associated with adverse events that might have an impact on adherence. The patient recruitment period (criterion 7) was restricted because the first protease inhibitor (lopinavir/Kaletra®, AbbVie Inc., North Chicago, Illinois, USA) was approved by the U.S. Food and Drug Administration in September 2000 and the European Medical Association in April 2001. This was the beginning of a new era for HAART regimes, and it involved a change in clinical outcomes as well as intake regimes, side effects and, consequently, adherence. Adherence is difficult to measure, and several definitions of adherence were used, making it difficult to compare different interventions only on the basis of adherence rates. Furthermore, adherence has no direct patient benefit. Therefore, it is necessary to focus on clinical outcomes when comparing interventions (criterion 4). Clinical endpoints were chosen because it was not expected that patient-relevant outcomes (e.g. AIDS, death and quality of life) would be analysed in the trials and, moreover, viral load and CD4 cell count are validated surrogates. As adherence interventions are specific in their settings and patient profiles, a comparison between developed and less/least developed countries did not seem reasonable. Thus, RCTs conducted exclusively in regions of WHO mortality stratum A were considered.
Titles and abstracts were screened by two reviewers independently according to a priori defined inclusion criteria. The full texts of potentially eligible articles were then obtained. Two reviewers assessed the eligibility of the full texts according to the review inclusion criteria. Differences between reviewers were discussed until a consensus was reached. The references of the included publications were checked for further potentially relevant publications. If the fulfilment of the inclusion criteria could not be assessed because of a lack of information in the publication, the corresponding authors were contacted. If the authors did not reply within 4 weeks, the respective inclusion criterion was considered as not fulfilled, and the trial was excluded.
The data were extracted in standardized tables. Information on the region and setting of the trial, special inclusion criteria regarding gender and mental disorders, patient characteristics (see Appendix 3), intervention(s) and control, the duration of intervention and follow-up, the definition and measurement of adherence and the results were summarized in these tables. Gender and mental disorders were extracted because both were expected to have a strong influence on adherence. If outcomes were measured at multiple time-points, only the last assessment of the intervention and follow-up period was extracted. For different measures of the same clinical outcome (e.g. undetectable viral load and mean viral load), the measure assessed at baseline and follow-up was presented. The results were considered statistically significant if the P-value was < 0.05 or the authors declared the results in their publication to be statistically significant without stating a level of significance. In the latter case, a note was made. All data were extracted by one reviewer and checked by a second for quality assurance.
The Cochrane risk of bias tool was used for methodological quality assessment of the included trials.
Because of the obvious nature of adherence-enhancing interventions, the blinding of patients and personnel was not applicable. The respective quality criteria were therefore unnecessary and not assessed. Therefore, the following six evaluation criteria were used to assess the risk of bias.
Was the random sequence generated adequately?
Was the allocation concealment adequate?
Was the outcome assessment/analysis blinded?
Was the analysis performed according to intention-to-treat?
Were the results not reported selectively?
Were there no other sources of bias?
The criteria were rated as 'fulfilled', 'not fulfilled' or 'not applicable'. The original Cochrane risk of bias tool also allows the category of 'unclear'. In the assessment presented here, the category 'unclear' was judged as 'not fulfilled'. The quality assessment was performed by two reviewers independently, and discrepancies were resolved in a discussion or by involving an unbiased third person.
High heterogeneity was expected as a consequence of the diversity of existing adherence-enhancing interventions and different target populations. Therefore, a quantitative data synthesis using a meta-analysis was not conducted.
There was no study protocol for this review.
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