The finding: The aim of this systematic review and meta-analysis was to assess the impact of HIV on neurocognitive performance in perinatally HIV-infected children and adolescents compared to HIV exposed but uninfected and HIV-uninfected controls. Findings from the meta-analysis showed a statistically significant effect in between-group comparisons for 2 out of the 10 neurocognitive domains tested; executive function and processing speed were significantly more impaired. Effect size estimates were also calculated for between-group comparisons for each cognitive domain. Executive functioning and processing speed showed significant differences between groups. Additionally, when ranked according to effect size, working memory, processing speed, and executive functioning showed the largest between-group differences. Of the 22 studies that met inclusion criteria in the study, 6 were eligible for the meta-analysis. The remaining 16 studies were looked at qualitatively. Among these studies group differences were found for executive functioning, processing speed, working memory, and visual memory.

Strength and weaknesses: Strong evidence exists supporting the negative effect of HIV on global cognitive functioning in perinatally HIV-infected children and adolescents. This study fills an important gap in knowledge about the extent of cognitive impairment and which specific domains are most likely to be affected. Data sources included five electronic bibliographic databases. This study also used mean-effect size estimates to calculate the strength of the association between domain-specific impairment and HIV, enabling ranking of the domains in order of degree of impairment. The burden of perinatal HIV is greatest in sub-Saharan Africa, yet the majority of studies included occurred in developed countries. This disparity limits the generalizability of findings to resource challenged areas.

Relevance: Despite the overwhelming success of prevention of mother-to-child HIV transmission in developed countries, vertical transmission in resource-challenged areas remains problematic. Furthermore the relative paucity of knowledge about the degree of domain-specific cognitive impairment has been a barrier to the development of effective therapies. Individuals with perinatally acquired HIV are unique in that degeneration is occurring during rapid brain growth and development. Therefore, the characterization of impairments may lead to better prevention and treatment approaches tailored to the needs of this vulnerable group.

The finding: This study used a three-arm design to randomly assign HIV-positive adults with depression to receive 1) CBT for depression combined with a cognitive behavioral approach to enhance antiretroviral medication adherence (Life-Steps), CBT-AD; or 2) integrated supportive psychotherapy with Life-Steps adherence counseling, ISP-AD; or 3) a control group intervention comprising enhanced treatment as usual and Life-Steps, ETAU. The primary outcome was antiretroviral medication adherence at 4 months follow-up assessed via electronic pill bottle cap, Medication Event Monitoring System (MEMS). Secondary outcomes were depression severity as assessed with CESD, MADRS, and CGI scales, HIV RNA and CD4 cell count, at 4, 8, and 12 months follow-up visits. The results showed that CBT-AD outperformed ETAU on both depression and adherence measures at the end of the 4-month treatment period and subsequent 8-month follow-up. There was no significant difference in primary or secondary outcomes between the CBT-AD and ISP-AD arms. The authors conclude that integrating adherence counseling and evidence-based depression treatment offers advantages in HIV-positive individuals suffering from depression.

Strength and weaknesses: This full-scale efficacy trial extends positive findings from previous smaller trials and uses two active intervention arms as well as a less intensive comparison group. Findings can be used to inform cost-effective design of integrated HIV behavioral health care programs. The study included individuals who were virologically suppressed at baseline, thus limiting detection of an intervention effect with respect to secondary biological outcome measures. In addition, the use of a MEMS cap to assess adherence may result in either underestimation or overestimation of adherence. The use of three study sites expanded the potential available participants. However, location of sites in medical centers in the northeast in the USA limit generalizability of findings to less resource-rich areas. Similarly, the high level of training of staff supervising the treating clinicians limits the exportability of treatment.

Relevance: Effective HIV prevention depends on expanded HIV testing, engagement, and retention in care and adherence to antiretroviral medication which is essential for virologic suppression. Depression is highly prevalent in HIV-infected individuals and can disrupt success at any point along the continuum of care. In addition, treatment of depression alone will not insure adequate adherence to HIV medication regimens. This study adds to our current understanding of evidence-based interventions that target both depression and adherence and that can be adapted to a variety of settings. The study also offers insight into the specific kinds of interventions that may be required.