Early HIV viral suppression associated with subsequent 12-month treatment success among people living with HIV in South Africa.

BACKGROUND: We analyzed the STREAM (Simplifying HIV TREAtment and Monitoring) study to determine risk factors associated with HIV viraemia and poor retention 18 months after initiation of antiretroviral therapy (ART). METHODS: The STREAM study was an open-label randomized controlled trial in Durban, South Africa, that enrolled 390 people living with HIV presenting for their first HIV viral load measurement ~6 months after ART initiation. We used modified Poisson regression with robust standard errors to describe associations between baseline characteristics and three HIV outcomes 18 months after ART initiation: HIV viraemia (>50 copies/mL), poor retention in HIV care, and a composite outcome of poor retention in care and/or HIV viraemia. RESULTS: Approximately 18 months after ART initiation, 45 (11.5%) participants were no longer retained in care and 43 (11.8%) had viraemia. People with CD4 counts <200 and those with viraemia 6 months after ART initiation were significantly more likely to have viraemia 18 months after ART initiation (adjusted relative risk [aRR] 4.0; 95% confidence interval [CI] 2.1-7.5 and aRR 5.5; 95% CI 3.3-9.0, respectively). People who did not disclose their HIV status and had viraemia after ART initiation were more likely to not be retained in care 12 months later (aRR 2.6; 95% CI 1.1-6.1 and aRR 2.2; 95% CI 1.0-4.8). People with a CD4 count <200 and those with viraemia were more likely to not achieve the composite outcome 18 months after ART initiation. CONCLUSIONS: Viraemia after ART initiation was the strongest predictor of subsequent viraemia and poor care retention. Understanding early indicators can help target our interventions to better engage people who may be more likely to experience persistent viraemia or disengage from HIV care.

Behavioral Modeling and its Association with PrEP and ART Use in Ugandan HIV-Serodifferent Couples.

Integrating Pre-Exposure Prophylaxis (PrEP) delivery into Antiretroviral Therapy (ART) programs bridges the Human Immunodeficiency Virus (HIV) prevention gap for HIV-serodifferent couples prior to the partner living with HIV achieving viral suppression. Behavioral modeling is one mechanism that could explain health-related behavior among couples, including those using antiretroviral medications, but few tools exist to measure the extent to which behavior is modeled. Using a longitudinal observational design nested within a cluster randomized trial, this study examined the factor structure and assessed the internal consistency of a novel 24-item, four-point Likert-type scale to measure behavioral modeling and the association of behavioral modeling with medication-taking behaviors among heterosexual, cis-gender HIV-serodifferent couples. In 149 couples enrolled for research, a five-factor model provided the best statistical and conceptual fit, including attention to partner behavior, collective action, role modeling, motivation, and relationship quality. Behavioral modeling was associated with medication-taking behaviors among members of serodifferent couples. Partner modeling of ART/PrEP taking could be an important target for assessment and intervention in HIV prevention programs for HIV serodifferent couples.

Temporal dynamics of emotional processing: Parsing trial-wise variance of the late positive potential using Generalizability Theory.

The reliability of individual trial event-related potential (ERP) components extracted from electroencephalogram has been consistently questioned since ERP research began. This ambivalence is based on misunderstood assumptions stemming from Cronbach and Classical Test Theory. Contemporary methods allow for the reliability of individual ERP trials to be estimated and for analyses of these trial-level ERP components to be meaningfully parsed. We illustrate the use of Generalizability Theory procedures in estimating the reliability of trial-level ERPs using the late positive potential (LPP), a neural measure of motivated attention toward emotionally evocative stimuli. Individuals (N = 88) completed a passive viewing task while continuous EEG was recorded. Variability in trial-level LPP responses was decomposed into facets corresponding to individual differences, chronological trial within block, stimulus type, their two-way interactions, and specific stimuli. We estimated various reliability coefficients and found that both overall and category-specific person-level LPP estimates have good-to-excellent reliability, while the reliability of within-person differences (i.e., change) between arousal categories was fair for the early LPP. These results were generally consistent across time windows, but were highest early in the LPP time course. We argue that investigating reliability using trial-level data allows researchers to pursue hypotheses focused on neurophysiological dynamics that unfold over the course of an experiment and not risk false inferences (i.e., ecological fallacy) when using person-level aggregates to deduce such processes. Moreover, such analyses provide information that allows researchers to optimize their protocols by potentially reducing the number of individual trials, burden on participants, and cost, while retaining sufficient reliability.

Do community measures impact the effectiveness of a community led HIV testing intervention. Secondary analysis of an HIV self-testing intervention in rural communities in Zimbabwe.

BACKGROUND: There is a growing body of evidence for the role that communities can have in producing beneficial health outcomes. There is also an increasing recognition of the effectiveness and success of community-led interventions to promote public health efforts. This study investigated whether and how community-level measures facilitate a community-led intervention to achieve improved HIV outcomes. METHODS: This is a secondary analysis of survey data from a cluster randomised trial in 40 rural communities in Zimbabwe. The survey was conducted four months after the intervention was initiated. Communities were randomised 1:1 to either paid distribution arm, where HIV self-test (HIVST) kits were distributed by a paid distributor, or community-led whereby members of the community were responsible for organising and conducting the distribution of HIVST kits. We used mixed effects logistic regression to assess the effect of social cohesion, problem solving, and HIV awareness on HIV testing and prevention. RESULTS: We found no association between community measures and the three HIV outcomes (self-testing, new HIV diagnosis and linkage to VMMC or confirmatory testing). However, the interaction analyses highlighted that in high social cohesion communities, the odds of new HIV diagnosis was greater in the community-led arm than paid distribution arm (OR 2.06 95% CI 1.03-4.19). CONCLUSION: We found some evidence that community-led interventions reached more undiagnosed people living with HIV in places with high social cohesion. Additional research should seek to understand whether the effect of social cohesion is persistent across other community interventions and outcomes. TRIAL REGISTRATION: PACTR201607001701788.

Teleneurocritical Care for Patients with Large Vessel Occlusive Ischemic Stroke Treated by Thrombectomy.

BACKGROUND: Teleneurocritical care (TNCC) provides 24/7 virtual treatment of patients with neurological disease in the emergency department or intensive care unit. However, it is not known if TNCC is safe, effective, or associated with similar outcomes compared with in-person neurocritical care. We aim to determine the effect of daily inpatient consults from TNCC on the outcomes of patients with large vessel occlusive acute ischemic stroke treated by thrombectomy. METHODS: A multicenter, retrospective cohort of consecutive patients ≥ 18 years old with acute ischemic stroke from a large vessel occlusion treated by thrombectomy were identified from 2018 to 2021 within a telehealth network of an integrated not-for-profit health care system in the United States. The primary end point was good functional outcome, i.e., modified Rankin Scale 0-3, at the time of hospital discharge in patients receiving in-person neurocritical care versus TNCC. RESULTS: A total of 437 patients met inclusion criteria, 226 at the in-person hospital (median age 67, 53% women) and 211 at the two TNCC hospitals (median age 74, 49% women). The rate of successful endovascular therapy (modified Thrombolysis in Cerebral Infarction score 2b-3) was not different among hospitals. Good functional outcome at discharge was similar between in-person neurocritical care and TNCC (in-person 31.4% vs. TNCC 33.5%, odds ratio 0.88, 95% confidence interval 0.6-1.3; p = 0.64). Only National Institutes of Health stroke scale and age were multivariable predictors of outcome. There were no differences in mortality (9.3% vs. 13.2%, p = 0.19), intensive care unit length of stay (2.1 vs. 1.9 days, p = 0.39), or rate of symptomatic intracerebral hemorrhage (6.8% vs. 6.6%, p = 0.47) between in-person neurocritical care and TNCC. CONCLUSIONS: Teleneurocritical care allows for equivalent favorable functional outcomes compared with in-person neurocritical care for patients with acute large vessel ischemic stroke receiving thrombectomy. The standardized protocols used by TNCC in this study, specifically the comprehensive 24/7 treatment of patients in the intensive care unit for the length of their stay, may be relevant for other health systems with limited in-person resources; however, additional study is required.

ART initiation among women newly diagnosed with HIV in a contraceptive trial in sub-Saharan Africa.

Current guidelines recommend starting antiretroviral therapy (ART) as soon as possible after HIV diagnosis to reduce morbidity, mortality and onward HIV transmission. We examined factors influencing ART initiation by women who seroconverted during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. ECHO, conducted between 2015 and 2018, enrolled HIV-negative, sexually active women, aged 16-35 years, from four African countries. Follow-up was 12-18 months, with quarterly HIV testing. Women with incident HIV infection received extensive counselling by trial staff and referral to local facilities for HIV care. Of 304 women with ≥90 days follow-up time since HIV diagnosis, 186(61.2%) initiated ART within 90 days, 69(22.7%) initiated after 90 days, and 49(16.1%) had not initiated by the end of the study. There were no statistically significant differences in characteristics among women who initiated ART ≤90 days versus those who did not. Frequent reasons for delayed or non-initiation of ART included not feeling ready to start ART and being newly diagnosed. In a large clinical trial, ART initiation was modest within 90 days of HIV diagnosis and grew to 84% with longer observation. Despite extensive counselling on the importance of early ART initiation, personal barriers delayed some women from starting ART.

The distinction between symptoms and traits in the Hierarchical Taxonomy of Psychopathology (HiTOP).

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirically and quantitatively derived dimensional classification system designed to describe the features of psychopathology and, ultimately, to replace categorical nosologies. Among the constructs that HiTOP organizes are "symptom components" and "maladaptive traits," but past HiTOP publications have not fully explicated the distinction between symptoms and traits. We propose working definitions of symptoms and traits and explore challenges, exceptions, and remaining questions. Specifically, we propose that the only systematic difference between symptoms and traits in HiTOP is one of time frame. Maladaptive traits are dispositional constructs that describe persistent tendencies to manifest features of psychopathology, whereas symptoms are features of psychopathology as they are manifest during any specific time period (from moments to days to months). This has the consequence that almost every HiTOP dimension, at any level of the hierarchy, can be assessed as either a trait or a symptom dimension, by adjusting the framing of the assessment. We discuss the implications of these definitions for causal models of the relations between symptoms and traits and for distinctions between psychopathology, normal personality variation, and dysfunction.

Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A Randomized Trial.

BACKGROUND: Effective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use for prevention. OBJECTIVE: To test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection. DESIGN: Household-randomized, double-blind, controlled trial of hydroxychloroquine postexposure prophylaxis. (ClinicalTrials.gov: NCT04328961). SETTING: National U.S. multicenter study. PARTICIPANTS: Close contacts recently exposed (<96 hours) to persons with diagnosed SARS-CoV-2 infection. INTERVENTION: Hydroxychloroquine (400 mg/d for 3 days followed by 200 mg/d for 11 days) or ascorbic acid (500 mg/d followed by 250 mg/d) as a placebo-equivalent control. MEASUREMENTS: Participants self-collected mid-turbinate swabs daily (days 1 to 14) for SARS-CoV-2 polymerase chain reaction (PCR) testing. The primary outcome was PCR-confirmed incident SARS-CoV-2 infection among persons who were SARS-CoV-2 negative at enrollment. RESULTS: Between March and August 2020, 671 households were randomly assigned: 337 (407 participants) to the hydroxychloroquine group and 334 (422 participants) to the control group. Retention at day 14 was 91%, and 10 724 of 11 606 (92%) expected swabs were tested. Among the 689 (89%) participants who were SARS-CoV-2 negative at baseline, there was no difference between the hydroxychloroquine and control groups in SARS-CoV-2 acquisition by day 14 (53 versus 45 events; adjusted hazard ratio, 1.10 [95% CI, 0.73 to 1.66]; P > 0.20). The frequency of participants experiencing adverse events was higher in the hydroxychloroquine group than the control group (66 [16.2%] versus 46 [10.9%], respectively; P = 0.026). LIMITATION: The delay between exposure, and then baseline testing and the first dose of hydroxychloroquine or ascorbic acid, was a median of 2 days. CONCLUSION: This rigorous randomized controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection. PRIMARY FUNDING SOURCE: Bill & Melinda Gates Foundation.

Realizing the Value of Nursing Through Innovative Regulation.

Nursing regulation is a specialty area of nursing practice that some may perceive as only performing licensing and disciplinary functions. However, highly effective boards strive to meet their mission of public protection through continuous innovation. This article describes several innovative programs initiated by a board of nursing. Among the examples include regulatory waivers during the pandemic, collaborations with stakeholder organizations, a resource for nursing peer-review committees, and an alternative remediation option for practice breakdown. With strong leadership and committed teams, regulation can both protect the public and play a part in actualizing the value of nursing.

The Veggie Van: Customer characteristics, fruit and vegetable consumption, and barriers to healthy eating among shoppers at a mobile farmers market in the United States.

OBJECTIVE: Mobile farmers markets may improve local food environments by increasing access to healthy food, yet research is limited. The purpose of this study was to describe customer characteristics and barriers to healthy eating among customers at a mobile farmers market called the Veggie Van. DESIGN: In 2016, a customer intercept design was used to survey English-speaking Veggie Van customers (n = 192; 70.5% survey response rate) aged ≥18 years on sociodemographic and health characteristics, normal daily consumption of fruit and vegetables (F/V) using the Health Information National Trends Survey screener, food acquisition and purchasing habits, and potential barriers to healthy eating. We compared customers to service area neighborhood residents. Within customers, we compared first-time and repeat customers, and those with low and high F/V consumption. RESULTS: Veggie Van customers were more likely to identify as non-Hispanic white and have a bachelor's degree than neighborhood residents. Participants were mostly female (76.0%) and non-Hispanic white (53.7%). Approximately half (45.0%) were first-time customers and many (41.7%) did not meet F/V consumption recommendations. In the total sample, cost was the most frequently reported barrier to healthy eating. Among repeat customers, those with low F/V consumption were more likely to report cost as a barrier than those with high F/V consumption (p = 0.02). Only 8.9% reported no transportation to buy healthy food. CONCLUSIONS: Veggie Van customers may not represent neighborhood residents. Although few participants met F/V recommendations, most had transportation to buy healthy food. Mobile markets have lower overhead costs and greater flexibility than traditional stores and can address geo-spatial barriers to food access, but should ensure that they are serving target customers.

Criterion A of the AMPD in HiTOP.

The categorical model of personality disorder classification in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (5th ed. [DSM-5]; American Psychiatric Association, 2013 ) is highly and fundamentally problematic. Proposed for DSM-5 and provided within Section III (for Emerging Measures and Models) was the Alternative Model of Personality Disorder (AMPD) classification, consisting of Criterion A (self-interpersonal deficits) and Criterion B (maladaptive personality traits). A proposed alternative to the DSM-5 more generally is an empirically based dimensional organization of psychopathology identified as the Hierarchical Taxonomy of Psychopathology (HiTOP; Kotov et al., 2017 ). HiTOP currently includes, at the highest level, a general factor of psychopathology. Further down are the five domains of detachment, antagonistic externalizing, disinhibited externalizing, thought disorder, and internalizing (along with a provisional sixth somatoform dimension) that align with Criterion B. The purpose of this article is to discuss the potential inclusion and placement of the self-interpersonal deficits of the DSM-5 Section III Criterion A within HiTOP.

Behavioral health care in solid organ transplantation in a pediatric setting.

This study examined the demographic, medical, and psychiatric characteristics of transplant patients across organ groups seen by transplant psychology/psychiatry clinicians at a pediatric institution between 2008 and 2014. Chart reviews were conducted to better understand the behavioral health care provided to SOT patients and the role of transplant-dedicated psychology and psychiatry clinicians. Transplant psychology/psychiatry was consulted a total of 1060 times on 399 unique SOT patients over a 6-year period. There were no significant differences in the distribution of age, sex, or ethnicity across organ groups. Common reasons for a consultation included pretransplant evaluation, anxiety, depression, agitation, and general coping. Rates varied by organ groups. Twenty percent of consults also received a psychopharmacological evaluation, with differences in rates between organ groups. Roughly one-third of patients required high frequency of transplant psychology/psychiatry involvement. Lung and heart patients had the highest utilization. Psychiatric diagnosis rates were identified, with adjustment (41.0%) and anxiety disorders (30.1%) being the most common. Pediatric psychology and psychiatry clinicians offer developmentally informed biopsychosocial approaches to treatment for SOT patients. Clarifying the prevalence and nature of behavioral health care provided by organ group can help pediatric providers better understand appropriate psychosocial interventions and resources utilized by this patient population and ultimately guide centers toward a more unified approach to care.

HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV-1-Exposed Seronegative Women on Oral Preexposure Prophylaxis.

Although nonhuman primate studies have shown that simian immunodeficiency virus/simian-human immunodeficiency virus (SIV/SHIV) exposure during preexposure prophylaxis (PrEP) with oral tenofovir can induce SIV immunity without productive infection, this has not been documented in humans. We evaluated cervicovaginal IgA in Partners PrEP Study participants using a subtype C primary isolate and found that women on PrEP had IgA with higher average human immunodeficiency virus type 1 (HIV-1)-neutralizing magnitude than women on placebo (33% versus 7%; P = 0.008). Using a cutoff of ≥90% HIV-1 neutralization, 19% of women on-PrEP had HIV-1-neutralizing IgA compared to 0% of women on placebo (P = 0.09). We also estimated HIV-1 exposure and found that the proportion of women with HIV-1-neutralizing IgA was associated with the level of HIV-1 exposure (P = 0.04). Taken together, our data suggest that PrEP and high levels of exposure to HIV may each enhance mucosal HIV-1-specific humoral immune responses in sexually exposed but HIV-1-uninfected individuals. IMPORTANCE: Although there is not yet an effective HIV-1 vaccine, PrEP for at-risk HIV-1-uninfected individuals is a highly efficacious intervention to prevent HIV-1 acquisition and is currently being recommended by the CDC and WHO for all individuals at high risk of HIV-1 acquisition. We previously demonstrated that PrEP use does not enhance peripheral blood HIV-1-specific T-cell responses in HIV-exposed individuals. Here, we evaluate for cervicovaginal HIV-neutralizing IgA responses in genital mucosal secretions of HIV-exposed women, which is likely a more relevant site than peripheral blood for observation of potentially protective immune events occurring in response to sexual HIV-1 exposure for various periods. Furthermore, we assess for host response in the context of longitudinal quantification of HIV-1 exposure. We report that HIV-neutralizing IgA is significantly correlated with higher HIV-1 exposure and, furthermore, that there are more women with HIV-1-neutralizing IgA in the on-PrEP group than in the placebo group.

Antiretroviral Therapy Initiation Is Not Associated With Risky Sexual Behavior Among Heterosexual Human Immunodeficiency Virus-Infected Persons in Serodiscordant Partnerships.

BACKGROUND: Few prospective studies have assessed whether antiretroviral therapy (ART) use is associated with changes in sexual risk behavior of human immunodeficiency virus (HIV)-infected persons in known HIV-serodiscordant partnerships. METHODS: We conducted a longitudinal analysis of HIV-infected persons with known uninfected partners enrolled in the Partners Pre-Exposure Prophylaxis Study in Kenya and Uganda. Antiretroviral therapy use and self-reported sexual behavior were ascertained every 3 months. We assessed the effect of ART on sexual risk behaviors using zero-inflated negative binomial regression. Primary outcomes were condomless vaginal sex acts, pregnancy incidence and new sexually transmitted infection diagnoses. RESULTS: We followed 1817 HIV-infected persons (58% women) for 864 person-years before ART initiation and 771 person-years after ART. Median CD4 and plasma viral load at ART initiation were 277 cells/µL and 4.18 log10 copies/mL. Antiretroviral therapy use was associated with a significant decrease in condomless vaginal sex acts with HIV-uninfected partners (0.65 vs 0.39 per month; rate ratio, 0.64; 95% confidence interval [CI], 0.55-0.75; P < 0.001), but not condomless vaginal sex acts with nonprimary partners (1.30 vs 1.04 per month; rate ratio, 0.94; 95% CI, 0.94-1.20; P = 0.62). Pregnancy incidence was lower after ART (13.2 vs 8.4 per 100 person-years; HR, 0.71; 95% CI, 0.60-0.84; P < 0.001). Incident sexually transmitted infection diagnoses were similar (odds ratio, 1.05; 95% CI, 0.86-1.29; P = 0.63). CONCLUSIONS: Substantial risk compensation did not occur after ART initiation among East African HIV-infected persons with known HIV-uninfected partners. These data inform modelling studies of ART for HIV prevention by suggesting that risky sexual behavior did not appear to offset decreased HIV infectiousness in this key population.

Transient Increase in Herpes Simplex Virus Type 2 (HSV-2)-Associated Genital Ulcers Following Initiation of Antiretroviral Therapy in HIV/HSV-2-Coinfected Individuals.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected persons beginning antiretroviral therapy (ART) has been incompletely characterized for herpes simplex virus type 2 (HSV-2). METHODS: We evaluated genital ulcer disease (GUD) and HSV-2-associated GUD at quarterly visits or when spontaneously reported at monthly visits in 3381 HIV/HSV-2-coinfected individuals in a placebo-controlled trial of suppressive acyclovir therapy to prevent HIV transmission, 349 of whom initiated ART during the study. Incidence was calculated for months before and after ART initiation, and incidence rate ratios (IRRs) were calculated. RESULTS: GUD incidence increased from 15.0 episodes per 100 person-years before ART to 26.9 episodes per 100 person-years in the first full quarter after ART initiation (IRR, 1.83;P= .03), and the incidence of HSV-2-associated GUD increased from 8.1 to 19.0 episodes per 100 person-years (IRR, 2.20;P= .02). Subsequently, the incidence of GUD was similar to that before ART, although the numbers were small. Persons receiving suppressive acyclovir had fewer GUD episodes, but the IRR after beginning ART was similar in the acyclovir and placebo groups. CONCLUSIONS: Initiation of ART in HIV/HSV-2-coinfected persons is associated with a transient increase in GUD and HSV-2 GUD. Acyclovir reduces the incidence of GUD but does not prevent an increase in GUD incidence during the first quarter following initiation of ART.

Acyclovir Prophylaxis Reduces the Incidence of Herpes Zoster Among HIV-Infected Individuals: Results of a Randomized Clinical Trial.

Human immunodeficiency virus (HIV)-infected persons have higher rates of herpes zoster than HIV-uninfected individuals. We assessed whether twice daily treatment with 400 mg of oral acyclovir reduces the incidence of herpes zoster in a randomized, double-blind, placebo-controlled trial among 3408 persons coinfected with HIV and herpes simplex virus type 2. During 5175 person-years of follow-up, 26 cases of herpes zoster occurred among those assigned acyclovir, compared with 69 cases among those assigned placebo (rates, 1.00 and 2.68/100 person-years, respectively), a relative decrease of 62% (hazard ratio, 0.38; 95% confidence interval, .24-.67; P < .001). Daily acyclovir prophylaxis significantly reduced herpes zoster incidence among HIV-infected persons.

Host genetic and viral determinants of HIV-1 RNA set point among HIV-1 seroconverters from sub-saharan Africa.

UNLABELLED: We quantified the collective impact of source partner HIV-1 RNA levels, human leukocyte antigen (HLA) alleles, and innate responses through Toll-like receptor (TLR) alleles on the HIV-1 set point. Data came from HIV-1 seroconverters in African HIV-1 serodiscordant couple cohorts. Linear regression was used to determine associations with set point and R(2) to estimate variation explained by covariates. The strongest predictors of set point were HLA alleles (B*53:01, B*14:01, and B*27:03) and plasma HIV-1 levels of the transmitting partner, which explained 13% and 10% of variation in set point, respectively. HLA-A concordance between partners and TLR polymorphisms (TLR2 rs3804100 and TLR7 rs179012) also were associated with set point, explaining 6% and 5% of the variation, respectively. Overall, these factors and genital factors of the transmitter (i.e., male circumcision, bacterial vaginosis, and use of acyclovir) explained 46% of variation in set point. We found that both innate and adaptive immune responses, together with plasma HIV-1 levels of the transmitting partner, explain almost half of the variation in viral load set point. IMPORTANCE: After HIV-1 infection, uncontrolled virus replication leads to a rapid increase in HIV-1 concentrations. Once host immune responses develop, however, HIV-1 levels reach a peak and subsequently decline until they reach a stable level that may persist for years. This stable HIV-1 set point represents an equilibrium between the virus and host responses and is predictive of later disease progression and transmission potential. Understanding how host and virus factors interact to determine HIV-1 set point may elucidate novel mechanisms or biological pathways for treating HIV-1 infection. We identified host and virus factors that predict HIV-1 set point in people who recently acquired HIV-1, finding that both innate and adaptive immune responses, along with factors that likely influence HIV-1 virulence and inoculum, explain ∼46% of the variation in HIV-1 set point.

Herpes Simplex Virus Suppressive Therapy in Herpes Simplex Virus-2/Human Immunodeficiency Virus-1 Coinfected Women Is Associated With Reduced Systemic CXCL10 But Not Genital Cytokines.

BACKGROUND: Herpes simplex virus type-2 (HSV-2) may heighten immune activation and increase human immunodeficiency virus 1 (HIV-1) replication, resulting in greater infectivity and faster HIV-1 disease progression. An 18-week randomized, placebo-controlled crossover trial of 500 mg valacyclovir twice daily in 20 antiretroviral-naive women coinfected with HSV-2 and HIV-1 was conducted and HSV-2 suppression was found to significantly reduce both HSV-2 and HIV-1 viral loads both systemically and the endocervical compartment. METHODS: To determine the effect of HSV-2 suppression on systemic and genital mucosal inflammation, plasma specimens, and endocervical swabs were collected weekly from volunteers in the trial and cryopreserved. Plasma was assessed for concentrations of 31 cytokines and chemokines; endocervical fluid was eluted from swabs and assayed for 14 cytokines and chemokines. RESULTS: Valacyclovir significantly reduced plasma CXCL10 but did not significantly alter other cytokine concentrations in either compartment. CONCLUSIONS: These data suggest genital tract inflammation in women persists despite HSV-2 suppression, supporting the lack of effect on transmission seen in large scale efficacy trials. Alternative therapies are needed to reduce persistent mucosal inflammation that may enhance transmission of HSV-2 and HIV-1.

Does Adherence Change When No One is Looking? Comparing Announced and Unannounced Tenofovir Levels in a PrEP Trial.

Differences between unannounced and announced tenofovir levels as measures of PrEP adherence are not well understood. In an ancillary adherence study involving one urban site (Kampala) and two rural sites (Kabwohe and Tororo) from the Partners PrEP study, 268 specimen pairs from chronologically proximal clinic and home visits were tested for plasma tenofovir levels. Comparing clinic and home specimens, 89 versus 89 % were classified as detectable (>0.31 ng/ml; p = 0.77), 87 versus 86 % as recent dosing (>10 ng/ml; p = 0.80), and 82 versus 80 % as steady-state (>40 ng/ml; p = 0.44). Mean difference between announced and unannounced drug levels, adjusted for specimen collection time was 3.2 ng/ml (p = 0.50) for Kabwohe, 23.2 ng/ml (p = 0.003) for Kampala and -3.3 ng/ml p = 0.69) for Tororo. In the setting of high adherence, plasma tenofovir levels tested at the clinic were categorically similar as levels tested at home; however, differences were seen between urban and rural settings.

Evaluating the effectiveness of patient education and empowerment to improve patient-provider interactions in antiretroviral therapy clinics in Namibia.

In order to increase patient active engagement during patient-provider interactions, we developed and implemented patient training sessions in four antiretroviral therapy (ART) clinics in Namibia using a "Patient Empowerment" training curriculum. We examined the impact of these trainings on patient-provider interactions after the intervention. We tested the effectiveness of the intervention using a randomized parallel group design, with half of the 589 enrolled patients randomly assigned to receive the training immediately and the remaining randomized to receive the training 6 months later. The effects of the training on patient engagement during medical consultations were measured at each clinic visit for at least 8 months of follow-up. Each consultation was audiotaped and then coded using the Roter Interaction Analysis System (RIAS). RIAS outcomes were compared between study groups at 6 months. Using intention-to-treat analysis, consultations in the intervention group had significantly higher RIAS scores in doctor facilitation and patient activation (adjusted difference in score 1.19, p = .004), doctor information gathering (adjusted difference in score 2.96, p = .000), patient question asking (adjusted difference in score .48, p = .012), and patient positive affect (adjusted difference in score 2.08, p = .002). Other measures were higher in the intervention group but did not reach statistical significance. We have evidence that increased engagement of patients in clinical consultation can be achieved via a targeted training program, although outcome data were not available on all patients. The patient training program was successfully integrated into ART clinics so that the trainings complemented other services being provided.