Rebecca Schaffer DDS
Bone Mineral Density (BMD) is stable in HIV+ cohorts established on highly active antiretroviral therapy (HAART). By contrast, cohorts initiating HAART show short-term accelerated BMD loss followed by BMD increase/stability as HAART takes effect.
Based on 37 observational studies, with just six including non-HIV-infected controls, HAART was found to be associated with stabilized BMD. In patients who were HAART-naïve (had never been on HAART) at baseline, there was accelerated loss of BMD which stabilized at one year after HAART initiation. HAART experience should be considered in health assessment and treatment planning.
In HIV+ individuals, is HAART associated with differences in bone mineral density (BMD) across time or when compared to uninfected individuals?
The authors conducted a comprehensive search of MEDLINE, EMBASE and the Web of Science. They also searched abstracts from relevant scientific meetings and hand searched references of obtained studies and published reviews. They included studies published in English that reported data only from adult participants, had an age/gender matched control group without HIV infection and reported BMD data at least 48 weeks apart. They excluded studies if BMD measurements were performed on different machines during the study. They performed a separate analysis of studies that otherwise met the inclusion criteria but did not have a non-HIV control group. The authors included randomized controlled trials conducted for other research purposes if they did not impact BMD. Two authors independently extracted data and resolved discrepancies by consensus. The review authors inspected funnel plots and used appropriate statistical methods to evaluate publication bias. When studies reported data on subgroups receiving differing HIV treatment regimens, the authors pooled the data for the various subgroups. The authors analyzed uncontrolled studies for percent change at 1, 2 and =2.5 years from baseline.
The search yielded six studies involving 779 HIV-infected participants with a comparable uninfected control group, and 31 studies involving 2026 HIV-infected participants without such a control group. The studies were all longitudinal. In the six primary studies, there was no significant difference between the percent change from baseline in either femoral neck or total hip BMD in HIV-infected cohorts compared with controls. There was a decrease of 0.6% in spine BMD; however, a small, undefined number of HIV+ participants in those six studies were not on HAART.
A meta-analysis of uncontrolled studies reporting changes in BMD from baseline yielded heterogeneous results. However, when HAART status at baseline was analyzed as a variable, those on HAART had stable or increasing BMD at one year. In contrast, participants who were HAART-naive at baseline had significant loss of BMD after HAART was initiated. The authors state that there was no evidence of publication bias.
The results indicate that, in HIV+ patients established on HAART, BMD is steady and comparable to that of non-HIV-infected individuals, matched for age and gender. Cohorts who are initiating HAART at baseline have short-term accelerated BMD loss followed by a longer period of BMD stability. Those HIV+ cohorts who were HAART-naive at study baseline continued to show losses in BMD. These losses decreased over time.
Source of Funding:
The Health Research Council of New Zealand provided funding for this systematic review.
Importance and Context:
Dental treatment plans need to consider a patient's medical status. Patients who are HIV+ and receiving HAART may have a more stable BMD than those who are HAART-naive. These data can be integrated into the treatment planning process, since a stable BMD is an indicator of the patient's overall health.
Strengths and Weaknesses of the Systematic Review:
The authors used accepted methods to identify studies included in the review and employed an independent review of the evidence. Only six cohort studies met the criteria for primary analysis, defined as the difference in the percent change in BMD from baseline in the HIV+ group, most of whom were receiving HAART, compared with the non-infected control group. In this first group of studies, the authors presented the data by measurement site. There was significant heterogeneity in results for total hip BMD. They also completed an analysis of publication bias. However, the authors did not show supporting data, and did not assess the quality of the included studies.
The authors performed secondary analysis on an additional 31 uncontrolled studies. They stratified the analysis according to HAART status at baseline, which reduced significant heterogeneity of the studies. Data reporting was complicated by the number of independent variables. The authors were careful to recognize the weakness of the evidence; however, for evidence arising from observational studies, a systematic review without meta-analysis may have been more appropriate.
Strengths and Weaknesses of the Evidence:
The strength of this review is compromised by the small number of controlled studies and the significant heterogeneity present in secondary analysis. The included studies were longitudinal in nature, but it is unclear if they were prospective, retrospective or both. In the group of six controlled studies, the exact number of HIV+ subjects on HAART was unknown. Thus, a pure "head-to-head" comparison of BMD changes in HIV+ individuals on HAART versus HIV+ individuals who were HAART naive is not possible. Additionally, one of the included studies had a 75 percent dropout rate at the two-year mark. Finally, A 0.6 percent difference with a tight confidence interval appears to be clinically insignificant.
Implications for Dental Practice:
Practitioners should obtain complete medical and social histories from patients prior to developing a comprehensive treatment plan. When developing treatment plans for patients who are HIV+, clinicians need to consider nutritional status, HAART status, and history of weight changes, all of which may be associated with changes in bone density, and in turn, overall health.