We also predicted that recent cocaine use would amplify the effects of historical use in HIV as assessed by traditional and ISDA memory metrics. Relative to other memory metrics, we posited that encoding would adversely be impacted given that both cocaine and HIV have been documented to impact frontostriatal networks . Data from 113 community-dwelling HIV infected participants were used for the current analysis. This sample was extracted from a prior study , which was funded by the National Institute on Drug Abuse . The initial study was adequately powered to detect the effects of . No control group was available in the sample . Participants were recruited from community health agencies in the Los Angeles area through fliers posted in infectious disease clinics at two University-affiliated medical centers. Exclusion criteria included meeting diagnostic criteria for lifetime or current history of psychotic spectrum or manic disorders and any neurological disorder other than HIV-infection . For our analyses, the participants were stratified by 1) recent cocaine use and 2) if participants ever met diagnostic criteria for cocaine dependence or abuse in their lifetime. The stratification for the recent cocaine abuse, participants 1) reported using cocaine within 4 weeks of testing and/or had positive urinalysis results for cocaine use on the day of testing or 2) denied cocaine use 4 weeks prior to testing and had negative cocaine urinalysis results . A period of four weeks was selected for self-report to ensure that there was sufficient time for such substances to adequately clear their system. Urine toxicology conducted on the day of testing, which screened for cocaine, amphetamine, cannabis,indoor growing racks and opiate metabolites. The stratification for presence or absence of lifetime cocaine dependence or abuse was determined by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorder 4th Edition, Clinical Version . HIV status was confirmed with ELISA and Western blot. Seventy percent of the HIV/ Coc+ , 63 percent of the HIV/Coc− , 65 percent of HIV/CocDx+ , and 72 percent of HIV/CocDx− participants met the Centers for Disease Control and Prevention diagnostic criteria for Acquired Immunodeficiency Syndrome .

There were no group differences in the proportion of participants meeting criteria for AIDS . All of the participants were on self-administered HAART at the time of testing. The CVLT-II is a verbal list-learning test comprised of 16 items that can be grouped into four semantic categories. The list is presented orally to participants over five learning trials, followed by a short-delay free and cued recall, long-delay free and cued recall, and recognition trials. The CVLT-II yields numerous indices. For the current study, we were interested primarily in the sum of items recalled across all five learning trials , short-delay free recall, and long-delay free recall. Item level data from the CVLT-II were evaluated via the Item Specific Deficit Approach , a quantitative process method for deriving indices of encoding, consolidation, and retrieval deficits. These indices have demonstrated increased sensitivity to cognitive impairment compared to traditional indices calculated from list-learning data . Furthermore, these indices seem to be less contaminated by other cognitive factors . The ISDA encoding deficit index is derived by summing the items that were not recalled at least three times during the five initial CVLT-II learning trials . The consolidation deficit index is calculated by summing the items that were recalled at least once during the list learning, but not recalled during either the short or long delay free or cued recall trials. The retrieval index is calculated via the sum of items that were recalled during list learning but recalled inconsistently across the short and long-delay free and cued recall trials . The consolidation index and retrieval index totals are divided by the number of items recalled at least once during the list learning trials to control for learning differences between groups.While the HIV/Coc+ and HIV/Coc− groups were well matched in terms of premorbid intelligence, age, education, sex, and history of depression , the HIV/Coc− group was comprised of a larger proportion of Caucasian participants than the HIV/Coc+ group. That said, ethnic/racial membership was not significantly associated with any of the dependent variables in the current study . Additionally, the HIV/Coc− had greater duration of lifetime cocaine and stimulant use, than the HIV/Coc+ group, while the HIV/Coc+ had a greater number of participants with positive cannabis toxicology. Total duration of cocaine and stimulant use was not associated with any of the dependent variables in the study . Similarly, positive cannabis toxicology was exclusive to HIV/Coc+ in our sample and was not associated with any of the dependent variables in the study .

While HIV/CocDx+ and HIV/CocDx− were well matched in terms of premorbid intelligence, age, education, sex, ethnicity, and history of depression , the HIV/CocDx− group had greater incidence of lifetime alcohol abuse and/or dependence and cannabis abuse and/or dependence than the HIV/CocDx+ group. That said, lifetime alcohol abuse and/or dependence and cannabis abuse and/or dependence were not significantly associated with any of the dependent variables in the current study . In order to determine the impact of cocaine use on CVLT-II performances, we performed 2 group X 2 cocaine use history ANOVAs for the CVLT-II total learning sum, CVLT-II short-delay free recall, CVLT-II long-delay free recall, and ISDA indices . A significance level of α <0.05 was used as the threshold for significance. To correct for family-wise error, we calculated q-values with a predetermined false discovery rate cut-off of .05 for each p value across all memory metrics .We hypothesized that 1) recent cocaine use will exacerbate encoding deficits and verbal memory difficulties in HIV infected individuals and 2) meeting lifetime diagnostic criteria for cocaine dependence and/or abuse would adversely impact memory performances, 3) recent cocaine use would amplify the effects of historical use in HIV, and 4) encoding would be adversely impacted over consolidation and retrieval. Our data partially supported these hypotheses. Specifically, using traditional verbal memory metrics that do not control for , recent cocaine use impacted total learning, short and long delay, and recognition discriminability, and interactive effects between recent use and historical use emerged only for the recognition discriminability metric. Specifically, the interactive effects revealed recognition discriminability performance differences in recent cocaine users with and without a lifetime history of cocaine abuse or dependence; the interaction further suggested that with abstinence, recognition discriminability performances of those with and without cocaine abuse and dependence are similar. Overall, the traditional memory metrics revealed general and non-specific findings that recent cocaine abuse and not historical use impacts all memory domains. However, given that traditional metrics do not account for inattention and dysexecutive symptoms , an alternative approach was employed as both cocaine and HIV influence frontostriatal networks subservient to these functions . Indeed, using the ISDA, our findings revealed that only encoding was compromised in the HIV/Coc+ group when compared to the HIV/Coc− group.

Additionally, using the ISDA, we found that historical cocaine use and/or dependence did not have an impact on encoding, consolidation, or retrieval. In contrasting traditional memory metrics and the ISDA, the ISDA memory metrics isolated statistically inferior performances to encoding, while the traditional metrics provided non-specific findings,micro green growing racks despite being statistically collinear to traditional memory metrics . Similar collinearity among memory metrics has been reported by other researchers . These findings speak to the incremental utility of the ISDA in an HIV setting and suggests that reduced memory performances in the context of HIV and cocaine use are likely secondary to disrupted learning, which is concordant with prior research suggesting frontostriatal involvement and reduced executive ability that likely impacts strategic encoding strategies . Of note, our findings are also in line with prior research supporting the notion that the deleterious effects of cocaine use on cognition in HIV are, at least to some extent, state-like in nature and transitory . Moreover, a recent longitudinal study found that in some cases, 1-year abstinence led to cognitive performances similar to that of healthy control participants . Our findings further add to the literature against the lasting impact of cocaine use ; however, given the cross-sectional nature of the study and a lack of healthy comparison subjects, we cannot affirm that reduced encoding will be fully ameliorated, although this study converges with other research that suggests performance comparable to HIV/Coc− groups. At first blush, our findings appear to differ from another study reporting no differences in verbal memory between HIV participants with and without cocaine use . However, in the Durvasula et al. study, HIV/Coc+ participants were younger and there is evidence to suggest that older individuals with HIV, even a remote history of stimulant use seems to have an effect as persons age . Additionally, the authors note that their findings may have been confounded by alcohol use and largely recreational drug users . The results of the current study underscore the importance of interventions that aid in the cessation of cocaine use among individuals with HIV. The immediate concern is that cocaine use could lead to worse cognitive status that could reduce HAART adherence. Indeed, declines in cognitive functioning , including memory , are associated with decreased medical compliance; this phenomenon also appears to be the case for cocaine use . This is a particularly vexing problem since cocaine-related verbal memory deficits may not only lead to worse functional outcomes, but active cocaine use may accelerate HIV replication , further highlighting the importance of targeted substance use/abuse interventions for persons with HIV. Our results have implications for clinical practice. Of notable importance, is the HIV/Coc+ memory profile of acquisition adjusted versus non-adjusted measurement of memory. Our findings highlight the importance of clinically correcting for inattention and a decline in executive ability , especially in the context of HIV and cocaine given the neurocircuitry involved . Relying solely on traditional metrics can be misleading, as seen in this study. Specifically, memory performances should adjust for acquisition, if memory is being evaluated . Additionally, HIV-related memory deficits are associated with decreases in medical compliance and daily functioning , so additional memory deficits caused by cocaine use could potentially exacerbate functional impairment in areas such as medication management, driving, employment, money management, cooking, and shopping . Additionally, our data suggest recommendations that specifically target the HIV-associated memory deficits, such as methods that improve the acquisition of new information rather than retrieval practice . Finally, our findings also offer hope and incentive to patients, suggesting that abstinence from cocaine may confer cognitive benefit. While our study suggests that recent, not past, cocaine use exacerbates verbal memory difficulties in HIV/AIDS via greater encoding deficits, our study also suffered from some limitations. The study did not include a healthy control group or a HIV-negative group with a history of cocaine use. Such comparisons would have allowed for a more detailed analysis and stronger conclusions about the independent, additive, and interactive effects of HIV serostatus and cocaine use. As such, this study can only speak to the effects of recent COC use in the setting of HIV and without a normative sample, differences observed between groups may not represent clinically relevant discrepancies . Nevertheless, discrepancies between healthy comparisons and participants with HIV are well documented . Our study evaluated the impact of cocaine use in HIV only on verbal memory and is a notable limitation, as other research has demonstrated discrepancies in attention, working memory, psychomotor speed, and executive functions . The present study utilized a cross-sectional design. A longitudinal and within-subjects design, in which participants’ performances are assessed while accounting for natural variation in the level of cocaine use over time, would have allowed us to better ascertain the impact of cocaine use on verbal memory in persons with HIV. Additionally, Finally, our methodology for determining history of cocaine use entailed self-report and urinalysis screen; while urinalysis is very accurate in this regard, it is only effective for a limited temporal window and, thus, we had to rely on self-reports regarding cocaine use that occurred several weeks prior to urine collection. That said, future research should also consider whether there are thresholds in terms of duration and severity of cocaine use that are related to long term declines in verbal memory in individuals with HIV. The incidence of HIV infection remains high among minority men who have sex with men.