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Antibody levels predict vaccine efficacy Symptomatic COVID-19 infection can be prevented by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. A “correlate of protection” is a molecular biomarker to measure how much immunity is needed to fight infection and is key for successful global immunization programs. Gilbert et al . determined that antibodies are the correlate of protection in vaccinated individuals enrolled in the Moderna COVE phase 3 clinical trial (see the Perspective by Openshaw). By measuring binding and neutralizing antibodies against the viral spike protein, the authors found that the levels of both antibodies correlated with the degree of vaccine efficacy. The higher the antibody level, the greater the protection afforded by the messenger RNA (mRNA) vaccine. Antibody levels that predict mRNA vaccine efficacy can therefore be used to guide vaccine regimen modifications and support regulatory approvals for a broader spectrum of the population. —PNK

Background We estimated the effect of initiating virologically suppressive antiretroviral therapy (ART) during acute HIV infection versus chronic HIV infection (AHI vs. CHI) on CD4/CD8 ratio normalization. Setting A prospective clinical cohort study. Methods We included patients initiating ART with AHI and CHI between 2000 and 2015 and compared time from ART initiation to the first normal CD4/CD8 ratio (defined as CD4/CD8 ≥1) using Kaplan-Meier curves and multivariable Cox proportional hazards models. Patient time was censored at virologic failure, lost to follow-up, or death. We also characterized CD4, CD8, and CD4/CD8 trajectories over the first 3 years of ART. Results The 1198 patients were 27% female and 60% African American, with a median age of 37 years (interquartile range 28-47) at ART initiation. The 83 AHI patients were more likely male, younger, and of white race, than CHI patients. After 2 years of suppressive ART, 70% of AHI patients achieved a normal CD4/CD8 ratio, compared to 6%-38% of CHI patients, with greater likelihood of normalization at higher baseline CD4 counts. Time to normalization was shortest among AHI patients, followed by CHI patients with higher baseline CD4. The adjusted hazard ratio for time to normalization for AHI patients compared to CHI patients with baseline CD4 >350 was 4.33 (95% CI: 3.16 to 5.93). Higher baseline CD4/CD8 ratio was also associated with time to normalization (adjusted hazard ratio 1.54; 1.46, 1.63, per 0.1 increase in ratio). Conclusions Initiating ART during AHI at higher baseline CD4 cell counts and CD4/CD8 ratios was associated with shorter time to CD4/CD8 ratio normalization.

Objectives: Tenofovir alafenamide, a prodrug of tenofovir, produces higher PBMC concentrations of tenofovir diphosphate (tenofovir-dp) than tenofovir disoproxil fumarate. To understand tenofovir alafenamide’s mucosal tissue distribution and its implications for pre-exposure prophylaxis, we characterized tenofovir-dp in female genital tract (FGT) and lower gastrointestinal (GI) tissues. Methods: Healthy seronegative women were given 5, 10 or 25 mg of tenofovir alafenamide (n = 8/group). Each participant provided plasma, PBMC and cervical, vaginal and rectal tissue samples over 14 days. Plasma, cell lysate and tissue homogenate concentrations were analysed by LC-MS/MS. Dose proportionality was declared in plasma and PBMCs if the natural log AUC versus natural log dose regression line 90% CI was within 0.57–1.43. In vitro tenofovir-dp formation was assessed in PBMCs and ectocervical (Ect1/E6E7) and vaginal (VK2/E6E7) cells incubated in 0.5 and 10 μM tenofovir alafenamide or tenofovir. clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT02357602","term_id":"NCT02357602"}}NCT02357602. Results: Following single doses of 5, 10 and 25 mg, median (IQR) tenofovir plasma AUC0–14 days was 52.8 (49.5–59.6), 78.1 (68.2–86.9) and 169.7 (131.2–211.4) ng·h/mL and tenofovir-dp PBMC AUC0–14 days was 2268 (1519–4090), 4584 (3113–5734) and 9306 (6891–10785) fmol·h/106 cells, respectively. Tenofovir was quantifiable in 52% and 92% of FGT and GI tissues, whereas tenofovir-dp was quantifiable in only 5% and 19% of FGT and GI tissues, respectively. Plasma tenofovir and PBMC tenofovir-dp were dose proportional (90% CI = 0.87–1.15 and 0.62–1.02, respectively). In vitro tenofovir-dp was 1.7–17-fold higher in epithelial cells than PBMCs. Conclusions: After tenofovir alafenamide dosing in vivo, tenofovir-dp was unquantifiable in most tissues (91%) although cervical and vaginal epithelial cells efficiently formed tenofovir-dp from tenofovir alafenamide in vitro. These findings warrant further investigation of tenofovir alafenamide’s pharmacology.

Background For the prevention and control of chronic diseases, two strategies are frequently highlighted: that public health should be evidence based, and that it should develop a multisectoral approach. At the end of a natural experimental study of the health impacts of new transport infrastructure, we took the opportunity of a knowledge exchange forum to explore how stakeholders assessed, negotiated and intended to apply multisectoral evidence in policy and practice at the intersection of transport and health. We aimed to better understand the challenges they faced in knowledge exchange, as well as their everyday experiences with working in multisectoral remits. Methods In 2015, we conducted participant observation during an interactive event with 41 stakeholders from national and local government, the third sector and academia in Cambridge, UK. Formal and informal interactions between stakeholders were recorded in observational field notes. We also conducted 18 semistructured interviews reflecting on the event and on knowledge exchange in general. Results We found that stakeholders negotiated a variety of challenges. First, stakeholders had to negotiate relatively new formal and informal multisectoral remits; and how to reconcile the differing expectations of transport specialists, who tended to emphasise the importance of precedence in guiding action, and health specialists’ concern for the rigour and synthesis of research evidence. Second, research in this field involved complex study designs, and often produced evidence with uncertain transferability to other settings. Third, health outcomes of transport schemes had political traction and were used strategically but not easily translated into cost-benefit ratios. Finally, knowledge exchange meant multiple directions of influence. Stakeholders were concerned that researchers did not always have skills to translate their findings into understandable evidence, and some stakeholders would welcome opportunities to influence research agendas. Conclusions This case study of stakeholders’ experiences indicates that multisectoral research, practice and policymaking requires the ability and capacity to locate, understand and communicate complex evidence from a variety of disciplines, and integrate different types of evidence into clear business cases beyond sectoral boundaries. Electronic supplementary material The online version of this article (doi:10.1186/s12889-016-3940-x) contains supplementary material, which is available to authorized users.

The Internet and mobile devices are increasingly used by men who have sex with men to find potential partners. Lack of partner information, besides e-mail addresses or user profiles, limits the ability to adequately perform partner notification by traditional means and test those at high risk. To streamline North Carolina Internet Partner Notification (IPN) services, University of North Carolina at Chapel Hill collaborated with the North Carolina Division of Public Health beginning in July 2011 to formalize state IPN and text messaging for partner notification (txtPN) policies and centralize notification practices by designating a single IPN/txtPN field coordinator within the University of North Carolina at Chapel Hill.We compared the number of IPN and txtPN contacts initiated and their outcomes in July 1, 2011, to June 30, 2012, and compared with outcomes in January 1, 2010, to December 31, 2010, the year before the collaboration.Overall, 362 IPN contacts were initiated compared with 133 initiated in 2010. More than half (59.1%) were black; mean age was 28.8 years. Almost all were men who have sex with men (83.7%). Approximately two-thirds (n = 230; 63.5%) of contacts were successfully notified using centralized IPN. Seven new cases of HIV infection, 11 new cases of syphilis, and 19 known previous HIV-positive persons were identified. Text messaging for partner notification was used for 29 contacts who did not initially respond to traditional notification or IPN; 14 (48%) responded to txtPN in a median time of 57.5 minutes (interquartile range, 9-2708).Centralization of IPN services augmented partner detection of new HIV and syphilis diagnoses. Text messaging for partner notification represents a potentially effective method for augmenting traditional partner services. In addition, IPN and txtPN allow identification of HIV-infected persons in need of linkage to care.