Impact of Symptomatic HIV- Related Neurocognitive Disorders in Survival of HIV- Infected Individuals: A Systematic Review and Meta-Analyses
Background: HIV- related symptomatic neurocognitive disorders (SNCD) negatively influence the survival of affected patients. We conducted this meta-analysis to provide pooled estimates of mortality risk attributable to SNCD. Methods: MEDLINE, Google scholar, Cochrane library PsycINFO and EMBASE were the data bases thoroughly searched up to April 2014. Two parallel meta-analyses were performed to derive hazard ratio (HR) and relative risk (RR) of mortality from 7 and 6 studies respectively. The level statistical heterogeneity in the included studies was assessed using I-squared (I2) statistic while metaregression and subgroup analyses mainly explored clinical and methodological heterogeneity. Other assessments were analyses for publication bias, small study effect, single study effect and study quality. Results: Thirteen studies with satisfactory quality met the inclusion criteria. A total of 84 421 HIV+ individuals across 21 countries from Europe and America were involved. Subjects with SNCD have more than twice risk of death compared to subjects without SNCD: HR=2.1, 95% confidence interval (CI)=1.52-2.58; RR=2.46, 95% CI=1.63-3.69. The estimated HR translates in to 72% probability of subjects with SNCD dying earlier than subjects without SNCD. Risk of mortality is associated with declining CD4 cell count (p=0.038) and neurocognitive impairment in psychomotor and memory domains. In subgroup analyses, there was no significant difference in mortality risk with respect to HAART utilization, type of SNCD and availability of demographically adjusted normative scores. Despite limiting generalizability of findings to sub-Saharan Africa, inclusion of studies conducted in developed countries reduces confounding and increases the accuracy of defining pooled estimates. Conclusion: HIV- related SNCD negatively influence survival in affected patients. Routine care of these patients should include neurocognitive screening preferably with a battery assessing domains that are predictive of mortality such as psychomotor and memory domains.