We compared demographic and behavioral characteristics between HIV-infected and HIV uninfected recruited partners by using two-tailed t tests and two-tailed x2 analyses. Because both index and recruited partners were occasionally represented in multiple different partnerships, mixed-effects logistic modeling was performed for genetic linkage and new HIV diagnoses. The UCSD Human Research Protections Program approved the study protocol, consent and all study related procedures. All study participants provided voluntary, written informed consent before any study procedures were undertaken.A total of 574 ART-naive individuals were newly diagnosed with AEH and offered partner services between 1996 and 2014. Among those index clients, 107 provided contact information sufficient to successfully identify and test partner [6/87 index clients diagnosed with AEH between 1996 and 2000, 33/ 128 between 2001 and 2004, 41/192 between 2005 and 2009 and 27/167 between 2010 and 2014]. These 107 index cases identified 119 recruited partners and 128 distinct partnerships . Only for two recruited partners, needle sharing was identified as the most likely mode of HIV transmission . There were nine individuals who served as both index case and recruited partner in distinct partnerships .The majority of both, index cases and recruited partners were non-Hispanic white men , MSM . The median age of index cases and recruited partners was not significantly different . Behavioral risks were also not significantly different between AEH index cases and recruited partners . In addition, there were no significant demographic or behavioral risk differences between HIV infected and HIV-uninfected recruited partners except for age . Of the 128 distinct partnerships identified, 52 were HIV serodiscordant,sliding growing tables and the remaining 76 were HIV seroconcordant. Paired HIV resistance test sequences were available in 62 of 76 seroconcordant partnerships and demonstrated genetic linkage in 38 of these partnerships.
Genetic linkage between the index case and recruited partner was used to identify putative transmission pairs and was observed in 50% of recruited partners with AEH and 50% of recruited partners with chronic HIV infection. Behavioral risks were not significantly different between index cases who were part of a genetic cluster and those who were not . Evaluation of the time between identification of the index case and recruited partners showed that those recruited partners enrolled within 30 days of their index were significantly more likely to be newly diagnosed with HIV and genetically linked to their index than partners identified later. The results were robust to whether partnerships were treated as independent or were corrected for belonging to multiple partnerships in the mixed-effects framework.We found that partner services for persons with AEH represents an effective tool to find HIV-unaware persons, particularly when partner services is performed within 30 days of diagnosis. Importantly, more than a third of the newly HIV-diagnosed recruited partners were still in the acute and early phases of HIV infection, that is the phase with the greatest risk of HIV transmission. Partner services also identified putative transmission partners, with genetically linked partners representing 61% of the seroconcordant partnerships. Finally, partner services identified a high-risk HIV-uninfected cohort, whose risk behaviors did not differ from those newly diagnosed with HIV infection. The HIV epidemic is propagated by HIV unawares, particularly during the phase of AEH. We demonstrated that HIV screening within the sexual contact network of persons diagnosed with AEH is an effective strategy to identify HIV unawares in early stages of HIV infection. In this study, one out of three recruited partners was newly diagnosed with HIV infection and one out of seven with AEH. This was 12 times higher than the overall yield of voluntary community-based HIV screening of MSM with the SD PIRC , the HIV-screening program used to identify the index participants in this study. Also, the recruited partners identified in this study represented a more high-yield cohort than previously documented. In two prior studies of partner services in AHI, 7–10% of all recruited partners identified were newly diagnosed with HIV, as compared with 33% in this study. Partner services might contribute to broader public health goals to end the epidemic. Although we found a decrease over time in the number of recruited partners , which may be explained in part by the success of anonymous, internet-based sexual networks, partner services continued to be high yield in terms of identifying HIV-positive individuals .
Another key finding was that the immediacy of partner services was essential. Partners identified in the first 30 days of a new AEH diagnosis were more likely to yield a new HIV diagnosis and a putative transmission link to the index case . In addition, 29% of genetic linkages occurred in partnerships in which the recruited partner also had AEH, showing that partner services coupled with phylogenetic analysis could potentially be an effective tool in identifying and targeting real-time transmission outbreaks among AEH persons. The HIV-uninfected recruited partners in this study reported behavioral risks that were comparable with AEH-infected index cases. Because they belonged to the sexual network of an individual with high infectivity, and because their risk behaviors did not differ from HIV-infected recruited partners, this group may represent ideal candidates for focused HIV-prevention services, including preexposure prophylaxis . Limitations of this study included the observational study design and the convenience sampling used to identify the study cohort. Further, this study was performed among MSM and in San Diego, among whom the HIVepidemic may differ from other areas of the world. Despite the fact that new HIV diagnoses within this studies were based on laboratory findings, self-report , and also checked against local HIV clinical and research databases, we can’t rule out that a proportion of recruited partners classified as newly diagnosed may, in fact, have been diagnosed with HIV before. Also, our study participants identified fewer recruited partners when compared with two prior studies of partner services . This is most likely because field-services were not provided in this study, as compared with the two prior studies in which partner services was performed by the local public health departments. In conclusion, our study indicates that provision of partner services to persons with AEH within the first 30 days of diagnosis represents an effective tool for finding HIV-unaware persons, including those with AEH who are at greatest risk of HIV transmission. In addition, partner services in this setting identifies HIV-uninfected partners who may greatly benefit from targeted prevention services, such as PrEP. These findings may suggest that in settings in which time and funding are too limited to perform partner services in all new HIV diagnoses, partner services should be focused on individuals diagnosed with AEH and performed within 30 days of diagnosis. Increased focus of partner services on individuals with AEH in these settings may potentially improve partner services delivery by clinicians and public health departments,curing weed identification of HIV-unawares and persons during AEH and identification of a high-risk HIV-uninfected cohort appropriate for prioritized prevention services and PrEP.
Taken together, these could translate into a larger impact on HIVepidemic control than partner services has had to date. Modeling studies evaluating the downstream effects of targeted partner services, that is the effects of combined identification and treatment of high-transmission risk persons, PrEP in those found to be HIV-uninfected and also real-time identification of AEH outbreaks are needed. These studies would further elucidate the impact of partner services in persons with AEH on epidemic control.The symposium addressed the intricate relationship between epilepsy and other medical conditions. Dr Scott Mintzer kicked off the symposium with his talk “Epilepsy & Heart Disease: Tips for the Consultant.” He identified the impacts of anticonvulsants on the cardiovascular system and the interactions between antiepileptic drugs and cardiac medications. Hepatic enzyme inducing anticonvulsants are associated with worse lipid profiles and vascular risk markers and reduce the efficacy of some cardiovascular medications, such as statins.1 Older anticonvulsants, such as carbamazepine, may even be associated with increased risk of myocardial ischemia. Dr Steven Pacia presented “Syncope and Other Seizure Mimics,” where he reviewed key clinical features that distinguish seizures from syncope and other seizure mimics such as migraine, transient ischemic attacks, metabolic disorders, non-epileptic psychogenic seizures, transient global amnesia, and sleep disorders. There is a broad differential diagnosis for episodic loss of awareness. Some, such as prolonged QT syndrome, should not be missed.2 Dr. Andres Kanner led the discussion on “Do Psychotropic and Antibiotic Drugs Cause Seizures? A Review of the Evidence.” He reviewed selection of antibiotics and psychiatric medications that would minimize seizure risk. Therapeutic doses of serotonin and norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, and tricyclic antidepressants appear to be associated with reduced seizure incidence, though overdoses of these classes of medications can be associated with increased risk of seizures.Bupropion and clomipramine were the exceptions to the rule, and seizure risk was increased with these medications compared to placebo. Antibiotics may increase the risk of seizures. The mechanism by which antibiotic lower seizure threshold may be decreased GABAergic activity. Dr Page Pennell discussed the management of AEDs during pregnancy to optimize seizure control and pregnancy outcomes in her talk “Seizure Management during Pregnancy.” Her presentation reviewed the teratogenic risk of AEDs and other pregnancy outcomes including “small for gestational age” .Valproate was also associated with lower IQ in childhood and increased risk of autism. On the other hand, folate prescribed before pregnancy or at start of pregnancy was associated with higher IQ and lower risks of autism. There are changes in pharmacokinetics of AEDs during pregnancy and dose adjustments are needed to maintain seizure control. Dr Jeanne Young discussed “Anticonvulsants and the Skin Hypersensitivity”. Dr Young emphasized the diversity in hypersensitivity associated with AEDs, distinguishing drug rash based on pathophysiology and clinical characteristics, and recognizing clinical features that could alert us to severe cutaneous adverse reactions.
The most common type of reaction is a morbilliform rash with erythematous papules or plaques due to immune complex deposition and cell-mediated immunity. These rashes characteristically begin 7 to 10 days after starting medication and typically resolve in 2 to 3 weeks. Patients usually feel well, though they may complain of pruritis. Interestingly, in some cases it is possible to “treat through” the rash, or re-challenge later with the same medication, with the patient under close observation by dermatology. Signs characteristic of more severe drug reactions are swelling of the face, presence of pustules, bullae, or vesicles, dusky or painful lesions, mucous membrane involvement, or signs of systemic involvement. Morbilliform skin eruptions beginning later than expected along with systemic symptoms and patient feeling ill are more concerning for progressing to Drug Rash with Eosinophilia and Systemic Symptoms syndrome.The neurobiology of memory has long been a central issue in epilepsy, particularly for syndromes involving mesial temporal lobe structures. While Ramon y Cajal first detailed the neuroanatomical structure of the hippocampus more than 100 years ago,it was the well-known case of “H.M.” that revealed the prominent role of the hippocampal formation and related structures in declarative memory.Patients undergoing temporal lobe resection for control of pharmacoresistant seizures may experience postoperative memory decline. Preoperative reorganization of the posterior hippocampus with transfer of function to contralateral and extratemporal structures including anterior cingulum and insula may be a key factor in preservation of memory function,and there may be a role for memory functional magnetic resonance imaging studies in individualized outcome prediction.There is also evidence that the choice of surgical approach has important implications for postoperative memory outcomes.Even apart from surgical intervention, memory deficits are a common comorbidity in epilepsy. At the cellular level, seizure induced epigenetic dysregulation likely plays an important— but little understood role. Abnormally regulated BDNF DNA methylation was explored in a rodent temporal lobe epilepsy model, and was shown to have a dual role in modulating both epileptiform abnormalities and memory impairments.Memory consolidation is an important mechanism supporting long-term memory that may also be disrupted by epileptiform activity. Studies of human multi-scale and animal recordings demonstrated locally recorded cortical replay of waking patterns during subsequent sleep periods.This process involves an intricate coordination of cortical up and down states, hippocampal sharp-wave ripples and thalamocortical spindle activity, with distinct roles played by the anterior and posterior hippocampus. Finally, building on the previous year’s symposium, early results from a recent high-profile study of the use of cortical electrical stimulation to improve memory function were presented.