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BackgroundAdherence to antiretroviral (ARV) therapy is critical for achieving HIV RNA suppression in people living with HIV and for preventing HIV infection in uninfected individuals using preexposure prophylaxis. However, a high level of adherence can be challenging to achieve for people living with HIV on lifelong ARVs and for HIV-negative individuals using daily preexposure prophylaxis who are not at daily risk for HIV infection. Current biological measures of adherence are invasive and use bioanalytical methods that do not allow for real-time feedback during a clinic visit. This study was designed to test the feasibility and acceptability of using MedViewer, a novel, minimally invasive, hair-based assay that measures longitudinal ARV drug adherence in real time and provides an output for provider-patient discussion. ObjectiveThe primary objectives were to investigate the feasibility of delivering the MedViewer results as planned, the acceptability of participation in a discussion of the MedViewer results, and the appropriateness of using MedViewer for adherence counseling. The secondary objectives were to investigate additional dimensions of feasibility, acceptability, and appropriateness of using the MedViewer test during a routine clinic visit for people with HIV. MethodsThe proposed study was a single-arm cross-sectional study among patients receiving HIV care and providers of HIV care in a southeastern infectious disease clinic. The study originally planned to implement the MedViewer test with 50 eligible patients who were living with HIV across 2 viral load strata (undetectable or detectable plasma HIV RNA over the previous 2 years), administer brief visit-specific questionnaires to all patient and provider participants, and conduct qualitative in-depth interviews and quantitative end-line questionnaires with a subsample of patient participants (n=30) and all provider participants. ResultsThe Establishing Novel Antiretroviral Imaging for Hair to Elucidate Nonadherence study was funded by the National Institute of Allergy and Infectious Diseases and approved by the local institutional review board on November 4, 2019. Provider participant enrollment began on January 17, 2020, and patient participant enrollment began on January 22, 2020. Participant enrollment was halted on March 16, 2020, because of the COVID-19 pandemic (16 providers and 10 patients on study). Study activities resumed on February 2, 2021, with COVID-19 modifications approved by the local institutional review board. Participant enrollment closed on October 8, 2021, and data collection closed on November 15, 2021. In total, 36 unique patient participants, representing 37 samples, and 20 provider participants were enrolled. Data analysis and manuscript writing will take place throughout 2023. ConclusionsWe anticipate that the data collected through this study will provide important insights regarding the feasibility, acceptability, and appropriateness of incorporating new real-time longitudinal, minimally invasive adherence tests into routine clinical care and identify potential barriers to medication adherence among patients. Trial RegistrationClinicalTrials.gov NCT04232540; https://clinicaltrials.gov/ct2/show/NCT04232540 International Registered Report Identifier (IRRID)RR1-10.2196/41188

The HIV-1 viral inhibition assay (VIA) measures CD8 T cell-mediated inhibition of HIV replication in CD4 T cells and is increasingly used for clinical testing of HIV vaccines and immunotherapies. The VIA has multiple sources of variability arising from in vitro HIV infection and co-culture of two T cell populations. Here, we describe multiple modifications to a 7-day VIA protocol, the most impactful being the introduction of independent replicate cultures for both HIV infected-CD4 (HIV-CD4) and HIV-CD4:CD8 T cell cultures. Virus inhibition was quantified using a ratio of weighted averages of p24+ cells in replicate cultures and the corresponding 95% confidence interval. An Excel template is provided to facilitate calculations. Virus inhibition was higher in people living with HIV suppressed on antiretroviral therapy (n=14, mean: 40.0%, median: 43.8%, range: 8.2 to 73.3%; p < 0.0001, two-tailed, exact Mann-Whitney test) compared to HIV-seronegative donors (n = 21, mean: -13.7%, median: -14.4%, range: -49.9 to 20.9%) and was stable over time (n = 6, mean %COV 9.4%, range 0.9 to 17.3%). Cross-sectional data were used to define 8% inhibition as the threshold to confidently detect specific CD8 T cell activity and determine the minimum number of culture replicates and p24+ cells needed to have 90% statistical power to detect this threshold. Last, we note that, in HIV seronegative donors, the addition of CD8 T cells to HIV infected CD4 T cells consistently increased HIV replication, though the level of increase varied markedly between donors. This co-culture effect may contribute to the weak correlations observed between CD8 T cell VIA and other measures of HIV-specific CD8 T cell function.

Abstract Background The sexual and reproductive health (SRH) status of female sex workers is influenced by a wide range of demographic, behavioural and structural factors. These factors vary considerably across and even within settings. Adopting an overly standardised approach to sex worker programmes may compromise its impact on some sub-groups in local areas. Methods Records of female sex workers attending clinic-, community-, or hotel-based health services in Johannesburg (n = 1422 women) and Pretoria (n = 408 women), South Africa were analysed. We describe the population’s characteristics and identified factors associated with sexual and reproductive health outcomes, namely HIV status; previous symptomatic sexually transmitted infection (STI); modern contraceptive use and number of child dependents. Results The women in Johannesburg were less likely than those in Pretoria to have HIV (42.2% vs 52.9%), or previous symptomatic STIs (44.3% vs. 8.3%), and were 1.4 fold less likely to have child dependents (20.1% vs. 15.3%). About 43% of women in Johannesburg were Zimbabwean and 40% in Pretoria. Of concern, only about 15% of women in both sites were using modern contraceptives. Johannesburg women were also more likely to access health services at a hotel (85.0% vs. 80.6%) or clinic (5.7% vs. 0.5%), to have completed secondary education (57.1% vs. 36.0%), and moved house more than twice during the past year (19.6 vs. 2.0%). In both cities, risk of HIV rose rapidly with age (23.8%–58.2% vs. 22.0%–64.8%). Of interest, HIV prevalence was considerably higher in those with consistent condom use with one’s main partner than inconsistent users. Conclusions Sex worker populations are heterogeneous. Local health programmes must prioritise services that reflect the variety and complexity of sex worker needs and behaviours, and should be designed in consultation with sex workers. Segmenting sex worker populations according to age, country of origin and place of service delivery, and training healthcare providers accordingly, could help prevent new HIV infections, improve adherence to antiretroviral treatment and increase uptake of SRH services.

Acute HIV infection (AHI) is a critical phase of infection when irreparable damage to the immune system occurs and subjects are very infectious. We studied subjects with AHI prospectively to develop better treatment and public health interventions.Cross-sectional screening was employed to detect HIV RNA positive, antibody negative subjects. Date of HIV acquisition was estimated from clinical history and correlated with sequence diversity assessed by single genome amplification (SGA). Twenty-two cytokines/chemokines were measured from enrollment through week 24.Thirty-seven AHI subjects were studied. In 7 participants with limited exposure windows, the median exposure to HIV occurred 14 days before symptom onset. Lack of viral sequence diversification confirmed the short duration of infection. Transmission dates estimated by SGA/sequencing using molecular clock models correlated with transmission dates estimated by symptom onset in individuals infected with single HIV variants (mean of 28 versus 33 days). Only 10 of 22 cytokines/chemokines were significantly elevated among AHI participants at enrollment compared to uninfected controls, and only 4 participants remained seronegative at enrollment.The results emphasize the difficulty in recruiting subjects early in AHI. Viral sequence diversity proved accurate in estimating time of infection. Regardless of aggressive screening, peak viremia and inflammation occurred before enrollment and potential intervention. Given the personal and public health importance, improved AHI detection is urgently needed.

In the present study, we analyzed the functional profile of CD8+ T-cell responses directed against autologous transmitted/founder HIV-1 isolates during acute and early infection, and examined whether multifunctionality is required for selection of virus escape mutations. Seven anti-retroviral therapy-naïve subjects were studied in detail between 1 and 87 weeks following onset of symptoms of acute HIV-1 infection. Synthetic peptides representing the autologous transmitted/founder HIV-1 sequences were used in multiparameter flow cytometry assays to determine the functionality of HIV-1-specific CD8+ T memory cells. In all seven patients, the earliest T cell responses were predominantly oligofunctional, although the relative contribution of multifunctional cell responses increased significantly with time from infection. Interestingly, only the magnitude of the total and not of the poly-functional T-cell responses was significantly associated with the selection of escape mutants. However, the high contribution of MIP-1β-producing CD8+ T-cells to the total response suggests that mechanisms not limited to cytotoxicity could be exerting immune pressure during acute infection. Lastly, we show that epitope entropy, reflecting the capacity of the epitope to tolerate mutational change and defined as the diversity of epitope sequences at the population level, was also correlated with rate of emergence of escape mutants.

A framework is described for understanding the schizophrenic syndrome at the brain systems level. It is hypothesized that over-activation of dynamic gesture and social perceptual processes in the temporal-parietal occipital junction (TPJ), posterior superior temporal sulcus (PSTS) and surrounding regions produce the syndrome (including positive and negative symptoms, their prevalence, prodromal signs and cognitive deficits). Hippocampal system hyper-activity and atrophy have been consistently found in schizophrenia. Hippocampal activity is highly related to activity in the TPJ and may be a source of over-excitation of the TPJ and surrounding regions. Strong evidence for this comes from in-vivo recordings in humans during psychotic episodes. The TPJ and PSTS play a key role in the perception (and production) of dynamic social, emotional and attentional gestures for the self and others (e.g., body/face/eye gestures, audiovisual speech, prosody). The single cell representation of dynamic gestures is multimodal (auditory, visual, tactile), matching the predominant hallucinatory categories in schizophrenia. Inherent in the single cell perceptual signal of dynamic gesture representations is a computation of intention, agency, and anticipation or expectancy (for the self and others). The neurons are also tuned or biased to detect threat related emotions. Abnormal over-activation in this system could produce the conscious hallucination of a voice (audiovisual speech), person or a touch. Over-activation could interfere with attentional/emotional gesture perception and production (negative symptoms). It could produce the unconscious feeling of being watched, followed or of a social situation unfolding along with accompanying perception of intent and agency inherent in those representations (delusions). Cognitive disturbances in attention, predictive social processing, agency, working memory, and a bias toward the perception of threat would also be predicted.

Evidence is reviewed for the existence of a core system for moment-to-moment social communication that is based on the perception of dynamic gestures and other social perceptual processes in the temporal-parietal occipital junction (TPJ), including the posterior superior temporal sulcus (PSTS) and surrounding regions. Overactivation of these regions may produce the schizophrenic syndrome. The TPJ plays a key role in the perception and production of dynamic social, emotional, and attentional gestures for the self and others. These include dynamic gestures of the body, face, and eyes as well as audiovisual speech and prosody. Many negative symptoms are characterized by deficits in responding within these domains. Several properties of this system have been discovered through single neuron recording, brain stimulation, neuroimaging, and the study of neurological impairment. These properties map onto the schizophrenic syndrome. The representation of dynamic gestures is multimodal (auditory, visual, and tactile), matching the predominant hallucinatory categories in schizophrenia. Inherent in the perceptual signal of gesture representation is a computation of intention, agency, and anticipation or expectancy (for the self and others). The neurons are also tuned or biased to rapidly detect threat-related emotions. I review preliminary evidence that overactivation of this system can result in schizophrenia.

While the varied theoretical frameworks of second wave feminism made possible critical interrogation of societal patterns of domination and oppression in view of the transformative goal of liberation, Michel Foucault’s conceptualization of power shifts contemporary feminist thought away from this binary field of relations towards more fundamental questions about gender constitution. Indeed, from the perspective of popular culture it would seem that challenges to rigid gender roles were a thing of the past, to which freedom and certain kinds of gender malleability were intrinsically tied. In fact gender roles continue to be defined in strict opposition to each other and sexist attitudes and practices continue, although increasingly disguised and unacknowledged. If liberation from the strictures of patriarchy is nothing but a lost illusion from the second wave, is there nonetheless a need for a resurgent feminist consciousness today? In this paper, I argue that this is the case, and attempt to show that “the work of the intellect” described by Foucault, must first be catalyzed by an experiential disruption, leading to recognition of what pragmatist philosopher John Dewey described as the “problematic situation.” While both Foucault and Dewey emphasize the necessity of problematization, Dewey’s methodology includes focus on envisioning desired outcomes. Here, my aim is not to resurrect an old idea of unconditioned liberation, but merely to reconsider whether and how experiential disruption and subsequent consideration of the problem might lead to a shift in social and self-consciousness, and create the possibility for change.