Persistence in a pharmacist-led, same-day PrEP program in Mississippi: a mixed-methods study.

INTRODUCTION: Mississippi has one of the highest rates of HIV in the United States but low PrEP uptake. Understanding patterns of PrEP use can improve PrEP initiation and persistence. METHODS: This is a mixed-method evaluation of a PrEP program in Jackson, Mississippi. Between November 2018-December 2019, clients at high risk for HIV attending a non-clinical testing site were referred to a pharmacist for same-day PrEP initiation. The pharmacist provided a 90-day PrEP prescription and scheduled a follow-up clinical appointment within three months. We linked client records from this visit to electronic health records from the two largest PrEP clinics in Jackson to determine linkage into ongoing clinical care. We identified four distinct PrEP use patterns, which we used for qualitative interview sampling: 1) filled a prescription and linked into care within three months; 2) filled a prescription and linked into care after three months; 3) filled a prescription and never linked into care; and 4) never filled a prescription. In 2021, we purposively sampled patients in these four groups for individual interviews to ascertain barriers and facilitators to PrEP initiation and persistence, using guides informed by the Theory of Planned Behavior. RESULTS: There were 121 clients evaluated for PrEP; all were given a prescription. One-third were less than 25 years old, 77% were Black, and 59% were cisgender men who have sex with men. One-quarter (26%) never filled their PrEP prescription, 44% picked up the prescription but never linked into clinical care, 12% linked into care at some point after three months (resulting in a gap in PrEP coverage), and 18% linked into care within 3 months. We interviewed 26 of 121 clients. Qualitative data revealed that cost, stigmas related to sexuality and HIV, misinformation about PrEP, and perceived side effects were barriers to uptake and persistence. Individuals' desire to stay healthy and the support of PrEP clinic staff were facilitators. CONCLUSIONS: The majority of individuals given a same-day PrEP prescription either never started PrEP or stopped PrEP within the first three months. Addressing noted barriers of stigma and misinformation and reducing structural barriers may increase PrEP initiation and persistence.

A Pharmacist-Led, Same-Day, HIV Pre-Exposure Prophylaxis Initiation Program to Increase PrEP Uptake and Decrease Time to PrEP Initiation.

Mississippi has one of the highest rates of HIV in the United States, but has low pre-exposure prophylaxis (PrEP) uptake, particularly among black men who have sex with men (MSM) and women. From November 2018 to May 2019, patients at high risk of HIV who tested negative for HIV at a nonclinical testing center in Jackson, Mississippi, were referred to an on-site clinical pharmacist for same-day PrEP initiation. The pharmacist evaluated patients for medical contraindications to PrEP, but no baseline labs were obtained. The pharmacist provided a PrEP prescription and scheduled a clinical appointment for patients within 6 weeks, at which time they were evaluated by a clinician and completed baseline labs. The pharmacist evaluated 69 patients for PrEP; 57% were MSM, 77% were black, and 65% were uninsured. All patients received a PrEP prescription; 83% received the prescription the same day and 97% received it within 5 days. Fifty-three (77%) of 69 clients filled the prescription; 87% of whom filled it within 1 week. Only 23 (43%) of 53 clients who filled their prescription attended their initial clinical appointment within 6 weeks of obtaining PrEP. There were no differences in PrEP initiation or retention by patient sex/gender. This pilot program suggests that an on-site pharmacist working in a nonclinical testing center in the southern United States can successfully initiate PrEP among predominately low-income black MSM. Future efforts should seek to better integrate laboratory testing into this demedicalized model of PrEP and to improve retention in care.

What does soil-transmitted helminth elimination look like? Results from a targeted molecular detection survey in Japan.

BACKGROUND: Japan is one of the few countries believed to have eliminated soil-transmitted helminths (STHs). In 1949, the national prevalence of Ascaris lumbricoides was 62.9%, which decreased to 0.6% in 1973 due to improvements in infrastructure, socioeconomic status, and the implementation of national STH control measures. The Parasitosis Prevention Law ended in 1994 and population-level screening ceased in Japan; therefore, current transmission status of STH in Japan is not well characterized. Sporadic cases of STH infections continue to be reported, raising the possibility of a larger-scale recrudescence of STH infections. Given that traditional microscopic detection methods are not sensitive to low-intensity STH infections, we conducted targeted prevalence surveys using sensitive PCR-based assays to evaluate the current STH-transmission status and to describe epidemiological characteristics of areas of Japan believed to have achieved historical elimination of STHs. METHODS: Stool samples were collected from 682 preschool- and school-aged children from six localities of Japan with previously high prevalence of STH. Caregivers of participants completed a questionnaire to ascertain access to water, sanitation and hygiene (WASH), and potential exposures to environmental contamination. For fecal testing, multi-parallel real-time PCR assays were used to detect infections of Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale and Trichuris trichiura. RESULTS: Among the 682 children, no positive samples were identified, and participants reported high standards of WASH. CONCLUSIONS: To our knowledge, this is the first STH-surveillance study in Japan to use sensitive molecular techniques for STH detection. The results suggest that recrudescence of STH infections has not occurred, and that declines in prevalence have been sustained in the sampled areas. These findings suggest that reductions in prevalence below the elimination thresholds, suggestive of transmission interruption, are possible. Additionally, this study provides circumstantial evidence that multi-parallel real-time PCR methods are applicable for evaluating elimination status in areas where STH prevalence is extremely low.

Testing for soil-transmitted helminth transmission elimination: Analysing the impact of the sensitivity of different diagnostic tools.

In recent years, an increased focus has been placed upon the possibility of the elimination of soil-transmitted helminth (STH) transmission using various interventions including mass drug administration. The primary diagnostic tool recommended by the WHO is the detection of STH eggs in stool using the Kato-Katz (KK) method. However, detecting infected individuals using this method becomes increasingly difficult as the intensity of infection decreases. Newer techniques, such as qPCR, have been shown to have greater sensitivity than KK, especially at low prevalence. However, the impact of using qPCR on elimination thresholds is yet to be investigated. In this paper, we aim to quantify how the sensitivity of these two diagnostic tools affects the optimal prevalence threshold at which to declare the interruption of transmission with a defined level of confidence. A stochastic, individual-based STH transmission model was used in this study to simulate the transmission dynamics of Ascaris and hookworm. Data from a Kenyan deworming study were used to parameterize the diagnostic model which was based on egg detection probabilities. The positive and negative predictive values (PPV and NPV) were calculated to assess the quality of any given threshold, with the optimal threshold value taken to be that at which both were maximised. The threshold prevalence of infection values for declaring elimination of Ascaris transmission were 6% and 12% for KK and qPCR respectively. For hookworm, these threshold values are lower at 0.5% and 2% respectively. Diagnostic tests with greater sensitivity are becoming increasingly important as we approach the elimination of STH transmission in some regions of the world. For declaring the elimination of transmission, using qPCR to diagnose STH infection results in the definition of a higher prevalence, than when KK is used.

Combined effectiveness of anthelmintic chemotherapy and WASH among HIV-infected adults.

INTRODUCTION: Current global helminth control guidelines focus on regular deworming of targeted populations for morbidity control. However, water, sanitation, and hygiene (WASH) interventions may also be important for reducing helminth transmission. We evaluated the impact of different potential helminth protective packages on infection prevalence, including repeated treatment with albendazole and praziquantel with and without WASH access. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cohort study nested within a randomized trial of empiric deworming of HIV-infected adults in Kenya. Helminth infections and infection intensity were diagnosed using semi-quantitative real-time PCR. We conducted a manual forward stepwise model building approach to identify if there are packages of interventions that may be protective against an STH infection of any species (combined outcome) and each helminth species individually. We conducted secondary analyses using the same approach only amongst individuals with no anthelmintis exposure. We used interaction terms to test for potential intervention synergy. Approximately 22% of the 701 stool samples provided were helminth-infected, most of which were of low to moderate intensity. The odds of infection with any STH species were lower for individuals who were treated with albendazole (aOR:0.11, 95%CI: 0.05, 0.20, p<0.001), adjusting for age and sex. Although most WASH conditions demonstrated minimal additional benefit in reducing the probability of infection with any STH species, access to safe flooring did appear to offer some additional protection (aOR:0.34, 95%CI: 0.20, 0.56, p<0.001). For schistosomiasis, only treatment with praziquantel was protective (aOR:0.30 95%CI: 0.14, 0.60, p = 0.001). Amongst individuals who were not treated with albendazole or praziquantel, the most protective intervention package to reduce probability of STH infections included safe flooring (aOR:0.34, 95%CI: 0.20, 0.59, p<0.001) and latrine access (aOR:0.59, 95%CI: 0.35, 0.99, p = 0.05). Across all species, there was no evidence of synergy or antagonism between anthelmintic chemotherapy with albendazole or praziquantel and WASH resources. CONCLUSIONS/SIGNIFICANCE: Deworming is effective in reducing the probability of helminth infections amongst HIV-infected adults. With the exception of safe flooring, WASH offers minimal additional benefit. However, WASH does appear to significantly reduce infection prevalence in adults who are not treated with chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00507221.

Prospects for elimination of soil-transmitted helminths.

PURPOSE OF REVIEW: Soil-transmitted helminths (STH) are endemic in 120 countries and are associated with substantial morbidity and loss of economic productivity. Although current WHO guidelines focus on morbidity control through mass drug administration (MDA), there is global interest in whether a strategy targeting disease elimination might be feasible in some settings. This review summarizes the prospects for switching from control to an elimination strategy. RECENT FINDINGS: STH control efforts have reduced the intensity of infections in targeted populations with associated reductions in morbidity. However, adults are not frequently targeted and remain important reservoirs for reinfection of treated children. Recent modeling suggests that transmission interruption may be possible through expanded community-wide delivery of MDA, the feasibility of which has been demonstrated by other programs. However, these models suggest that high levels of coverage and compliance must be achieved. Potential challenges include the risk of prematurely dismantling STH programs and the potential increased risk of antihelminthic resistance. SUMMARY: Elimination of STH may offer an opportunity to eliminate substantial STH-related morbidity while reducing resource needs of neglected tropical disease programs. Evidence from large community trials is needed to determine the feasibility of interrupting the transmission of STH in some geographic settings.

Correction: Impact of Age and Sex on CD4+ Cell Count Trajectories following Treatment Initiation: An Analysis of the Tanzanian HIV Treatment Database.

[This corrects the article DOI: 10.1371/journal.pone.0164148.].

The role of implementation science training in global health: from the perspective of graduates of the field's first dedicated doctoral program.

Bridging the 'know-do gap' is an enormous challenge for global health practitioners. They must be able to understand local health dynamics within the operational and social contexts that engender them, test and adjust approaches to implementation in collaboration with communities and stakeholders, interpret data to inform policy decisions, and design adaptive and resilient health systems at scale. These skills and methods have been formalized within the nascent field of Implementation Science (IS). As graduates of the world's first PhD program dedicated explicitly to IS, we have a unique perspective on the value of IS and the training, knowledge, and skills essential to bridging the 'know-do gap'. In this article, we describe the philosophy and curricula at the core of our program, outline the methods vital to IS in a global health context, and detail the role that we believe IS will increasingly play in global health practice. At this junction of enormous challenges and opportunities, we believe that IS offers the necessary tools for global health professionals to address complex problems in context and raises the bar of success for the global health programs of the future.

Impact of Age and Sex on CD4+ Cell Count Trajectories following Treatment Initiation: An Analysis of the Tanzanian HIV Treatment Database.

OBJECTIVE: New guidelines recommend that all HIV-infected individuals initiate antiretroviral treatment (ART) immediately following diagnosis. This study describes how immune reconstitution varies by gender and age to help identify poorly reconstituting subgroups and inform targeted testing initiatives. DESIGN: Longitudinal data from the outpatient monitoring system of the National AIDS Control Program in Tanzania. METHODS: An asymptotic nonlinear mixed effects model was fit to post-treatment CD4+ cell count trajectories, allowing for fixed effects of age and sex, and an age by sex interaction. RESULTS: Across 220,544 clinic visits from 32,069 HIV-infected patients, age- and sex-specific average CD4+ cell count at ART initiation ranged from 83-136 cells/mm3, long term asymptotic CD4+ cell count ranged from 301-389 cells/mm3, and time to half of maximal CD4+ reconstitution ranged from 3.57-5.68 months. CD4+ cell count at ART initiation and asymptotic CD4+ cell count were 1.28 (95% CI: 1.18-1.40) and 1.25 (95% CI: 1.20-1.31) times higher, respectively, for females compared to males in the youngest age group (19-29 years). Older patients started treatment at higher CD4+ counts but experienced slower CD4+ recovery than younger adults. Treatment initiation at greater CD4+ cell counts was correlated with greater asymptotic CD4+ cell counts within all sex and age groups. CONCLUSION: Older adults should initiate care early in disease progression because total immune reconstitution potential and rate of reconstitution appears to decrease with age. Targeted HIV testing and care linkage remains crucial for patient populations who tend to initiate treatment at lower CD4+ cell counts, including males and younger adults.

Prioritizing countries for interventions to reduce child mortality: tools for maximizing the impact of mass drug administration of azithromycin.

BACKGROUND: As new interventions to reduce childhood mortality are identified, careful consideration must be given to identifying populations that could benefit most from them. Promising reductions in childhood mortality reported in a large cluster randomized trial of mass drug administration (MDA) of azithromycin (AZM) prompted the development of visually compelling, easy-to-use tools that synthesize country-specific data on factors that would influence both potential AZM benefit and MDA implementation success. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the opportunity to reduce mortality and the feasibility of implementing such a program, creating Opportunity and Feasibility Indices, respectively. Countries with high childhood mortality were included. A Country Ranking Index combined key variables from the previous two Indices and applied a scoring system to identify high-priority countries. We compared four scenarios with varying weights given to each variable. Twenty-five countries met inclusion criteria. We created easily visualized tools to display the results of the Opportunity and Feasibility Indices. The Opportunity Index revealed substantial variation in the opportunity for an MDA of AZM program to reduce mortality, even among countries with high overall childhood mortality. The Feasibility Index demonstrated that implementing such a program would be most challenging in the countries that could see greatest benefit. Based on the Country Ranking Index, Equatorial Guinea would benefit the most from the MZA of AZM in three of the four scenarios we tested. CONCLUSIONS/SIGNIFICANCE: These visually accessible tools can be adapted or refined to include other metrics deemed important by stakeholders, and provide a quantitative approach to prioritization for intervention implementation. The need to explicitly state metrics and their weighting encourages thoughtful and transparent decision making. The objective and data-driven approach promoted by the three Indices may foster more efficient use of resources.