While approximately half of participants from both study samples reported experiencing recent violence, violence did not predict unsuppressed VL in either study. In combination, results may suggest differential effects of violence on women’s HIV outcomes in low-income populations where competing factors like homelessness and incarceration outweigh or otherwise obscure violence effects. Prior evaluations by the WHO of HIV clinical effectiveness in resource-limited regions led to the realization that HIV clinical guidelines developed in resource-rich areas were neither feasible nor realistic for resource-limited areas. Consequently, large-scale efforts were launched to develop public-health approaches specific to providing ART in resource-limited areas, taking into account the realities of lower-capacity health systems. Findings presented here suggest that translating clinical findings from resource-rich regions back to the same geographic area may not be feasible or realistic for populations experiencing severe disparity relative to the general population of PLWH. Analogous to taking the realities of lower capacity health systems into account, our results suggest that program development in high income areas must take the realities of disparity into account with interventions that not only consider housing and living conditions of extremely low-income individuals, but also prioritize them. Promising examples of such programs include several developed by the San Francisco Department of Public Health. For example, the “Linkage, Integration, Navigation, Comprehensive Services” program provides field-based navigators who offer short-term “intensive case management” to link homeless PLWH to HIV primary care. In addition,seedling grow rack the “HIV Homeless-Health Outreach Mobile Engagement” program provides stabilization and out of clinic health care to PLWH who have complex needs and are not engaged in care.
Examples also include community-based programs that address the overall well-being of people living on the street such as “Lava Mae,” a program that uses an approach known as “radical hospitality” to provide services, including mobile showers, toilets, clothing, food and employment assistance. Results presented here suggest that additional novel programs for WLWH following incarceration may further address unsuppressed VL in this population. There are several limitations regarding this study. First, VL data were obtained from public and UCSF-affiliated clinics, which may have left out individuals receiving care from private physicians outside of UCSF. However, only 8% of persons receiving HIV care were excluded based on the absence of VL data, likely making potential effects small. Second, participants for whom VL data within three months of a study visit did not exist and were therefore excluded were less likely to have an HIV case manager than participants who were included. Therefore, participants with case management and/or frequent clinic visits may have inflated results. While these individuals had more opportunity for their information to be inside the three-month window of time to assess VL following a study visit, we minimized potential bias from multiple measures by the use of robust standard errors, which down-weighted data for participants with relatively frequent results. We tested this assumption and confirmed that the number of observations was indeed not significantly associated with unsuppressed VL . In addition, while only two participants were newly diagnosed, time in care may be an unmeasured confounder in this study. Finally, study data came from one geographic location and focused on a high-risk population, which may limit generalizability. Future studies in different geographic areas that include more participants and multiple types of housing instability may contribute to a better understanding of variations in viral suppression.
Study strengths include a community-based probability sample of women with a history of housing instability; assessment of recent substance use and victimization at multiple time points; inclusion of multiple living conditions and a focus on the specific needs of extremely low-income women. Finally, study assessments were made in a resource-rich city where universal ART and integrated services were standard and viral suppression rates were high [58], which reduced unmeasured confounding due to service limitations.Cocaine use is common among individuals infected with human immunodeficiency virus . The high comorbidity between HIV and cocaine use highlights the importance of ascertaining the potential compounding effect of HIV infection and cocaine use on neuropsychological functioning . Neuroimaging studies have found significant overlap with respect to changes resulting from HIV infection and cocaine use. Both conditions are associated with grey and white matter pathology in frontal, temporal, and cerebellar regions . Despite widespread use of highly active anti-retroviral therapies and subsequent reduced incidence of HIV-related dementia and cognitive dysfunction , a subset of those with HIV still demonstrate neuropsychological deficits . HIV-associated cognitive impairments include deficits in attention , processing speed and psychomotor abilities , working memory , and executive functioning . Among the neuropsychological domains impacted by HIV, verbal memory deficits have received considerable attention. Verbal memory impairment in HIV is associated with functional declines, such as decreased employability, poor medical adherence, and other functional impairments . Some studies suggest that verbal memory impairment in HIV is due to a retrieval deficit, evidenced by impairments in recall in contrast to intact recognition or cued recall . Indeed, other work suggests that encoding deficits may also play a significant role in HIV-related verbal memory impairment. Specifically, studies have demonstrated HIV-related increased recency effects , decreased primacy effects , decreased semantic clustering , and deficient patterns of item recall during list learning . Moreover, other studies suggest that encoding deficits may be the primary contributing factor to HIV-associated memory impairment .
There are two likely explanations for these discrepant findings. First, differences in the HIV-associated memory deficit profile between studies may be related to variable use of HAART. Many of the studies that found both encoding and retrieval deficits were either conducted in the pre-HAART era or included participants that had low HAART adherence , whereas studies that found encoding deficits included participants on HAART —although there are exceptions . Second, researchers who argue that HIV is generally associated with encoding and not retrieval deficits point out that recall and recognition likely reflect discrepant processes. Specifically, recall appears to be the product of recollection while recognition seems to be comprised of both recollection and familiarity and it may be misleading to infer a retrieval deficit from recognition-recall discrepancies when recognition performances are greater than recall performances. That is, the recognition-recall discrepancies may be due to poor initial encoding rather and a true retrieval deficit. Cocaine is a potent stimulant that elevates synaptic levels of dopamine , norepinephrine , and serotonin , binds to DA, NE, and 5-HT transporters, and blocks neurotransmitter reuptake, although most of the literature has examined the effect of cocaine on the mesocorticolimbic DA pathway, since it has been posited to play an important role in addiction . Elevated DA levels lead to increased D1 and D2 receptor signaling and subsequent intracellular signaling pathways associated with G proteins . G proteins impact cyclic AMP-dependent protein kinase, which influences ion channels, vesicles, receptor expression, and glutamine neurotransmitters . These changes lead to increased excitability of the prefrontal cortex and are thought to account for the effects of cocaine . Neuroimaging studies have implicated structural, metabolic and white matter changes related to long-term use of cocaine , although recent critical review has questioned the methodology of these studies . Regarding the neuropsychological profile of cocaine use, acute effects of cocaine include enhanced response inhibition and psychomotor speed while chronic use is associated with deficits in processing speed , attention and working memory ,indoor grow racks executive functioning , and verbal memory . Studies examining abstinence from cocaine suggest at least partial reversal of cognitive deficits with 1 year of abstinence with residual deficits in reversal learning and emotional processing ; however, a recent systematic critical review by Frazer, Richards, and Keith warns against over interpreting group differences between cocaine users and non-users on cognitive measures and neuroimaging, as they may not indicate clinically significant discrepancies despite being statistically significant. Cocaine use in HIV has a synergistic impact on neuroimmune functioning, particularly the dopaminergic neurotransmission. While cocaine blocks DA transporters and acts as a reuptake inhibitor, the Tat protein of HIV functions as an allosteric modulator of DA transporter .
Consequently, in both cocaine use and HIV, elevated synaptic DA increases macrophages lead to neuroinflammation and accelerates the production of platelet monocyte complexes, which is related to HIV-associated neurocognitive disorder . Moreover, both cocaine use and HIV, directly and indirectly, impact the N-methyl-D-aspartate receptor , which represents a significant aspect of reward circuitry in the brain and it has been posited that changes NMDAR secondary to HIV infection may reinforce psycho stimulant abuse and addiction . In fact, HIV infected individuals have a stronger preference for the immediate effects of stimulant drugs over alcohol and nicotine . A recent neuroimaging study by Meade et al. of active cocaine use in HIV during intertemporal decision-making task revealed that cocaine use moderated the effects of HIV with clustered activations in the bilateral prefrontal cortices and cerebellum. Independently, cocaine use was associated with lower activation in bilateral frontal gyri and right insular and posterior parietal cortices while HIV was associated with higher activation in the visual cortex and reduced activation in bilateral prefrontal cortices and cerebellum and left posterior parietal cortex . From a neurocognitive perspective, as mentioned previously, chronic use of cocaine has a striking resemblance to the cognitive dysfunction associated with HIV, with overlap in impairments in attention, processing speed, verbal memory, and executive functioning. Of the aforementioned domains, verbal memory is a complex cognitive process that requires multiple abilities working in tandem and warrants further inspection—namely, dissecting what aspects of verbal memory is impacted . While some studies have found an impact on verbal memory , these finding may be impacted by reduced executive functioning and processing speed related to the synergistic impact of both cocaine and HIV. Specifically, Meade, Towe, Skalski, and Robertson found main effects for processing speed and executive functioning in HIV cocaine users with no significant effects for learning or memory. Traditional metrics of verbal memory of maybe confounded by attention and executive ability , which are domains that are dependent on the integrity of frontostriatal networks impacted by both HIV and cocaine use . Encoding metrics on verbal memory list tasks include learning slope, total correct on Trial 1, and other contrasts ; unfortunately, attentional difficulties are inherent in many neurological and psychiatric conditions can impact these scores . Similarly, consolidation metrics for verbal memory list tasks contrast total items recalled against recall following a delay with a decline signifying a loss of information or forgetting over time and another metric relies on proactive interference ; however, these metrics either provide non-specific findings of memory storage or do not account for initial learning . Retrieval metrics on verbal memory list tasks involve contrasting recall performances against recognition performances, although as mentioned previously, it may be misleading to infer a retrieval deficit from recognition recall discrepancies when recognition performances are greater than recall performances since these discrepancies may be due to poor initial encoding rather and a true retrieval deficit. The Item-Specific Deficit Approach is a psychometrically valid method that aims to mitigate the impact of inattention on encoding, consolidation, and retrieval on list-learning tasks . The ISDA was initially validated in a healthy comparisons sample, seropositive HIV, and traumatic brain injury , replicated in these populations , and has since been applied in other settings including amyotrophic lateral sclerosis , amnestic mild cognitive impairment , and Alzheimer disease . Most recently, Lueke and Lueke used the ISDA to evaluate the impact of mindfulness on encoding, consolidation, and retrieval. Generally, the ISDA has demonstrated superiority over traditional metrics, with one exception—Cattie et al. raised concerns about the incremental value of the ISDA and noted that the ISDA encoding index was collinear with other memory tests . In the current study, we attempted to ascertain the additive impact of recent and past cocaine use on the different aspects of verbal memory in a seropositive HIV sample using both traditional memory metrics and ISDA memory indices. Specifically, we examined if recent cocaine use impacted memory performances and also if a lifetime diagnosis of cocaine dependence or abuse impacted memory performances. We hypothesized that recent cocaine and not past use will adversely impact verbal memory given cocaine’s state-like effect on cognitive functioning . Additionally, a lifetime diagnosis of cocaine dependence or abuse and not subclinical use of cocaine the was hypothesized to adversely impact verbal memory given that some reach has posited at least some residual impact on brain structure .