Risk Of Seroconversion Research Articles

Use of routinely collected blood donation data for expanded HIV and Syphilis surveillance in Blantyre district, Malawi.

The World Health Organization recommends that all blood donations be screened for transfusion transmissible infections; these data are currently not incorporated into national disease surveillance efforts. We set out to use routinely collected data from blood donors in Blantyre district, Malawi to explore HIV and syphilis prevalence and identify sero-conversions among repeat donors. We conducted a retrospective cohort analysis of blood donation data collected by the Malawi Blood Transfusion Service from 2015 to 2021. All blood donations were routinely screened for HIV and syphilis. We characterized donor demographics as well as screening outcomes, including identifying sero-conversions among repeat donors who previously tested negative on their last donation. A total of 23,280 donations from 5,051 donors were recorded, with a median frequency of donations of 3 (IQR:2-6). Most donors were male (4,294; 85%) and students (3,262; 64.6%). Prevalence of HIV at first donation was 1.0% (52/5,051) and prevalence of syphilis was 1.6% (80/5,051); 52 HIV sero-conversions and 126 syphilis sero-conversions were identified, indicating an incidence rate per 1,000 person-years of 5.9 (95% CI: 4.7, 7.4) and 13.3 (95% CI:11.4, 15.4) respectively. Students had a lower prevalence of HIV and syphilis but higher risk of syphilis seroconversion. While blood donors are generally considered a low-risk population for HIV and syphilis, we were able to identify relatively high rates of undiagnosed HIV and syphilis infections among donors. Routinely collected data from national blood donation services may be used to better understand local HIV and syphilis epidemiology, with the potential to enhance disease surveillance systems. These findings may be used to identify priority prevention areas and populations in Blantyre district that can inform targeted interventions for improved disease prevention, testing and treatment.

The Prevalence of HIV Seroconversion in Healthcare Workers Following Sharp Injuries and Exposure to Biofluids.

Background and objective Workplace accidents (WPAs) are a common problem worldwide. They are often considered a public health concern due to the potential transmission of infections such as HIV, hepatitis B, and hepatitis C through sharp devices or direct exposure to biofluids. Post-exposure prophylaxis (PEP) has demonstrated effectiveness in such instances, especially immediately after exposure. The present study aimed to report the prevalence rate of HIV seroconversion following such exposure among healthcare workers (HCWs). Methods We conducted a cross-sectional study involving a database analysis of cases from 2015 to 2024. Central tendency measures were used to describe population characteristics, andrates were calculated using standard methods. Results A total of 514 HCWs were included in the study. The prevalence of WPAs was 13 per 100 HCWs. Regarding WPAs related to HIV exposure, the prevalence was 0.9 per 100 HCWs, with 0% seroconversion thanks to timely PEP. Conclusions WPAs related to HIV exposure are a serious issue for public health systems worldwide. Although protocols are available and no seroconversion cases were reported in the present study, PEP is not always accessible in several settings, increasing the risk of seroconversion. International public policy measures should be uniformly implemented to provide faster access to prophylaxis, educate the personnel, raise awareness about bloodborne diseases, and reduce excessive red tape.

Effectiveness of Frequent Viral Load Testing Plus Additional Interventions to Prevent HIV Transmission in Heterosexual, Serodiscordant Couples - Yunnan Province, China, 2019-2021.

HIV transmission among serodiscordant couples remains a persistent issue in China. However, the practice of combining counseling with antiretroviral therapies (ART) to enhance ART adherence is not widely implemented or recommended in Chinese health guidelines. This randomized controlled trial suggests that increased follow-up, counseling, and awareness of HIV risk can enhance ART compliance, thereby maximizing treatment efficacy. Early testing and counseling of serodiscordant couples, following the identification of a human immunodeficiency virus (HIV) positive spouse, is crucial for initiating ART and reducing the risk of seroconversion in the uninfected partner. Implementing a combination of ART and adjunct counseling in China is advisable.

Factors associated with PrEP-era HIV seroconversion in a 4-year U.S. national cohort of n = 6059 sexual and gender minority individuals who have sex with men, 2017-2022.

Community-based cohort studies of HIV seroconversion can identify important avenues for enhancing HIV prevention efforts in the era of pre-exposure prophylaxis (PrEP). Within individuals, one can assess exposure and outcome variables repeatedly and with increased certainty regarding temporal ordering. This cohort study examined the association of several risk factors with subsequent HIV seroconversion. We report data from a 4-year study (2017-2022) of 6059 HIV seronegative sexual and gender minority individuals who have sex with men who had indications for-, but were not using-, PrEP at enrolment. Participants completed repeat exposure assessments and self-collection of biospecimens for HIV testing. We examined the roles of race and ethnicity, socio-economic status, methamphetamine use and PrEP uptake over the course of follow-up in relation to HIV seroconversion. Over 4 years, 303 of the participants seroconverted across 18,421 person-years (incidence rate = 1.64 [95% CI: 1.59-1.70] per 100 person-years). In multivariable discrete-time survival analysis, factors independently associated with elevated HIV seroconversion risk included being Black/African American (adjusted risk ratio [aRR]: 2.44, 1.79-3.28), Hispanic/Latinx (1.53, 1.19-1.96), housing instability (1.58, 1.22-2.05) and past year methamphetamine use (3.82, 2.74-5.33). Conversely, time since study enrolment (24 vs. 12 months, 0.67, 0.51-0.87; 36 months, 0.60, 0.45-0.80; 48 months, 0.48, 0.35-0.66) and higher education (master's degree or higher vs. less than or equal to high school, 0.36, 0.17-0.66) were associated with reduced seroconversion risk. Compared to non-PrEP users in the past 2 years without a current clinical indication, those who started PrEP but then discontinued had higher seroconversion risk, irrespective of clinical indication (3.23, 1.74-6.46) or lack thereof (4.30, 1.85-9.88). However, those who initiated PrEP in the past year (0.14, 0.04-0.39) or persistently used PrEP in the past 2 years (0.33, 0.14-0.74) had a lower risk of seroconversion. Of all HIV seroconversions observed during follow-up assessments (12, 24, 36 and 48 months), methamphetamine was reported in the 12 months prior 128 (42.2%) times (overall). Interventions that acknowledge race and ethnicity, economic variables such as education and housing instability, and methamphetamine use are critically needed. Not only are interventions to engage individuals in PrEP care needed, but those that retain them, and re-engage those who may fall out of care are essential, given the exceptionally high risk of seroconversion in these groups.

Incidence and factors associated with PrEP discontinuation in France.

HIV pre-exposure prophylaxis (PrEP) is effective in preventing HIV, but some seroconversions occur due to poor adherence or PrEP discontinuation. Our objective was to estimate the incidence of PrEP discontinuation and describe the reasons and factors associated with discontinuations. A retrospective cohort was conducted in three French hospitals between January 2016 and June 2022. PrEP users who attended at least twice within 6 months during study period were included and followed up until December 2022. The incidence rate of PrEP discontinuation was estimated by censoring lost to follow up individuals. Factors associated with PrEP discontinuations were identified using a multivariate Cox model. A total of 2785 PrEP users were included, with 94% men and 5% transgender people. Median age was 35 years. By December 2022, 653 users had stopped PrEP (24%). The incidence rate was 10.8 PrEP discontinuations for 100 person-years (PY). The main causes of discontinuation were being in a stable relationship (32%), and not judging the treatment useful anymore (12%). Individuals who discontinued PrEP were younger [<29, HR = 1.45 (1.17-1.80)], and more likely to be women [HR = 2.44 (1.50-3.96)] or sex workers [HR = 1.53 (0.96-2.44)]. They were more likely to report PrEP side effects [HR = 2.25 (1.83-2.77)] or ≥2 sexually transmitted infections [HR = 1.87 (1.53-2.27)] during the last year. The incidence of PrEP discontinuations was quite low compared to rates observed in other cohorts. Users who stopped PrEP were sometimes still exposed to HIV, emphasizing the need for targeted interventions to prepare and support PrEP discontinuations and limit seroconversion risk.

HIV seroconversion and associated factors among seronegative pregnant women attending ANC in Ethiopia: an institution-based cross-sectional study.

In countries with limited resources, including Ethiopia, HIV is diagnosed using a rapid serological test, which does not detect the infection during the window period. Pregnant women who test negative for HIV on the first test may seroconvert throughout pregnancy. Women who are seroconverted during pregnancy may not have received interventions, as they are considered HIV-negative unless they are retested for HIV at the end of their pregnancy. Due to limited data on HIV seroconversion, this study aimed to measure the extent of HIV seroconversion and to identify associated factors among seronegative pregnant women attending ANC in Ethiopia. Institution-based cross-sectional study was conducted among HIV-negative pregnant women attending the ANC in Ethiopia between June and July 2020. Socio-demographic, clinical, and behavioral data were collected through face-to-face questionnaires and participants' records review. HIV retesting was performed to determine the current HIV status of pregnant women. The data collected were entered into Epi data version 4.4.1 and were exported and analyzed by SPSS version 25. A p-value < 0.25 in the bivariate analysis was entered into multivariable logistic regression analysis and a p-value of < 0.05 was considered statistically significant. Of the 494 pregnant women who tested negative for HIV on their first ANC test, six (1.2%) tested positive on repeat testing. Upon multivariable logistic regression, pregnant women who have had a reported history of sexually transmitted infections [AOR = 7.98; 95% CI (1.21, 52.82)], participants' partners reported travel history for work frequently [AOR = 6.00; 95% CI (1.09, 32.99)], and sexually abused pregnant women [AOR = 7.82; 95% CI (1.194, 51.24)] were significantly associated with HIV seroconversion. The seroconversion rate in this study indicates that pregnant women who are HIV-negative in early pregnancy are at an ongoing risk of seroconversion throughout their pregnancy. Thus, this study highlights the benefit of a repeat HIV testing strategy in late pregnancy, particularly when the risk of seroconversion or new infection cannot be convincingly excluded. Therefore, repeated testing of HIV-negative pregnant women in late pregnancy provides an opportunity to detect seroconverted pregnant women to enable the timely use of ART to prevent mother-to-child transmission of HIV infection.

Increasing Spiritual Beliefs are Associated With Lower HIV Incidence Among Black Men Who Have Sex With Men: Results From HPTN 061 Longitudinal Study.

There is a limited understanding about the impact of spiritual beliefs and activities on HIV seroconversion among black men who have sex with men (BMSM), which we investigate in this study. United States. The HIV Prevention Trials Network Study 061 collected demographic and biomedical assessments among BMSM across 6 United States cities for longitudinal analysis. Spiritual beliefs and spiritual activities are constructed composite scales. Bivariate analyses among 894 who provided data at 12-month follow-up compared men who seroconverted to HIV between baseline and 6 months with those who remained uninfected with HIV at 12 months. Cox proportional hazard regression among 944 men tested spiritual beliefs and activities on the longitudinal risk of HIV seroconversion adjusting for age and any sexually transmitted infection (STI). Among this sample, HIV incidence between baseline and 6 months was 1.69%, (95% confidence intervals [CI]: 1.04 to 2.77). Men who seroconverted to HIV were significantly younger than those who remained uninfected at the 12-month follow-up: (mean age 27, SD = 11 vs 37, SD = 12) and a higher proportion reported any STI (46.67% vs 11.39%, P < 0.01). A one-unit increase in spiritual beliefs was associated with lower hazard rate of seroconverting to HIV at follow-up [adjusted hazard ratio (aHR) = 0.37, 95% CI: = (0.16 to 0.87)]. Religious service attendance and spiritual activities were unrelated to seroconverting. Spirituality is important in the lives of BMSM. Biomedical and behavioral HIV prevention interventions should consider assessing spiritual beliefs in HIV care among BMSM.

Characterizing the evolving SARS-CoV-2 seroprevalence in urban and rural Malawi between February 2021 and April 2022: A population-based cohort study

ObjectivesThis study aimed to investigate the changing SARS-CoV-2 seroprevalence and associated health and sociodemographic factors in Malawi between February 2021 and April 2022. MethodsIn total, four 3-monthly serosurveys were conducted within a longitudinal population-based cohort in rural Karonga District and urban Lilongwe, testing for SARS-CoV-2 S1 immunoglobulin (Ig)G antibodies using an enzyme-linked immunosorbent assay. Population seroprevalence was estimated in all and unvaccinated participants. Bayesian mixed-effects logistic models estimated the odds of seropositivity in the first survey, and of seroconversion between surveys, adjusting for age, sex, occupation, location, and assay sensitivity/specificity. ResultsOf the 2005 participants (Karonga, n = 1005; Lilongwe, n = 1000), 55.8% were female and median age was 22.7 years. Between Surveys (SVY) 1 and 4, population-weighted SARS-CoV-2 seroprevalence increased from 26.3% to 89.2% and 46.4% to 93.9% in Karonga and Lilongwe, respectively. At SVY4, seroprevalence did not differ by COVID-19 vaccination status in adults, except for those aged 30+ years in Karonga (unvaccinated: 87.4%, 95% credible interval 79.3-93.0%; two doses: 98.1%, 94.8-99.5%). Location and age were associated with seroconversion risk. Individuals with hybrid immunity had higher SARS-CoV-2 seropositivity and antibody titers, than those infected. ConclusionHigh SARS-CoV-2 seroprevalence combined with low morbidity and mortality indicate that universal vaccination is unnecessary at this stage of the pandemic, supporting change in national policy to target at-risk groups.

Dietary Patterns and Anti-Flavivirus IgG Seroconversion in Colombian Children.

The burden of flaviviral infections, especially dengue and Zika, is high in the Americas. Malnutrition affects the risk and response to infections, but the role of diet on flaviviral infection risk is uncertain. The objective of this study was to investigate the relations between dietary patterns adherence and anti-flavivirus IgG seroconversion in children during a Zika epidemic in a dengue-endemic area of Colombia. In 2015-2016, we followed 424 anti-flavivirus IgG seronegative children aged 2 to 12 years for 1 year. Baseline data included children's sociodemographic, anthropometric, and dietary information collected through a 38-item food frequency questionnaire (FFQ). IgG testing was repeated at the end of follow-up. The primary exposure was adherence to each of four dietary patterns (animal foods, traditional, ultraprocessed foods, and prudent) that were identified from the FFQ through principal component analysis. Secondary exposures were intake frequencies of foods contributing to relevant patterns. We estimated risk of seroconversion by quartiles of adherence scores and compared them using relative risks (RR) and 95% CI from Poisson regression adjusted for sex, age, and socioeconomic status indicators. Seroconversion risk was 32.1%. Adherence to the traditional pattern was positively related to seroconversion. RR comparing fourth versus first quartiles of adherence was 1.52 (95% CI: 1.04-2.21; P trend = 0.02). Of the most representative foods in this pattern, potato and sugarcane water intake frequencies were related to increased seroconversion risk. In conclusion, adherence to a traditional foods pattern, including potatoes and sugarcane water, was positively associated with anti-flavivirus IgG seroconversion.

A new outbreak of HIV infection among people who inject drugs during the COVID-19 pandemic in Greece.

Multiple HIV outbreaks have been recorded among people who inject drugs (PWID) since 2010. During an intervention for PWID in 2019-2021 in Thessaloniki, Greece, an increasing number of HIV cases was documented. Here, we provide an analysis of this new outbreak. ALEXANDROS was a community-based program and participation included interviewing, rapid HIV/HCV tests, counselling and linkage to care. PWID were recruited through Respondent-Driven Sampling (RDS) in five sampling rounds. Crude and RDS-weighted HIV prevalence estimates were obtained. HIV incidence was estimated from data on 380 initially seronegative PWID with at least two tests. Multivariable Cox proportional hazards model was used to assess risk factors for HIV seroconversion. In total, 1,101 PWID were recruited. At first participation, 53.7% were current PWID, 20.1% homeless, 20.3% on opioid substitution treatment and 4.8% had received syringes in the past 12 months. HIV prevalence (95% CI) was 7.0% (5.6-8.7%) and an increasing trend was observed over 2019-2021 (p=0.002). Two-thirds of the cases (67.5%) were new diagnoses. HIV incidence was 7.0 new infections/100 person-years (95% CI:4.8-10.2). Homelessness in the past 12 months (HR:2.68; 95% CI:1.24-5.81) and receptive syringe sharing (HR:3.86; 95% CI:1.75-8.51) were independently associated with increased risk of seroconversion. By the end of the program, 67.3% of the newly diagnosed cases initiated antiretroviral treatment. A new HIV outbreak among PWID was documented in Greece during the COVID-19 pandemic with homelessness and syringe sharing being associated with increased risk of HIV acquisition. Peer-driven programs targeting the population of high-risk underserved PWID can be used to early identify emerging outbreaks and to improve linkage to HIV care.

FREQUENCY OF HEPATITIS C SEROCONVERSION IN CHRONIC KIDNEY DISEASE PATIENTS ON HEMODIALYSIS

Background: Haemodialysis increases Hepatitis-C seroconversion risk adversely affecting Chronic Kidney Disease (CKD) prognosis. This study aimed to determine the frequency of Hepatitis C seroconversion in chronic kidney disease patients on haemodialysis. Method: This cross-sectional study was conducted at Dialysis Unit of Ayub Teaching Hospital, Abbottabad from March 2016 to January 2019. A pre-designed proforma was used for data collection. A sample of 121 patients of dialysis dependent CKD was enrolled for the study through non-probability consecutive sampling. The Glomerular Filtration Rate (GFR) was re-estimated from serum creatinine to confirm the diagnosis using Modification of Diet in Renal Disease (MDRD) study equation. Patients who were Hepatitis C virus (HCV) negative at the start of dialysis, and became positive 3 months post-dialysis were considered having undergone seroconversion. Data were analysed using SPSS-16. Results: Out of 121 participants, 80 (66.1%) were male and 41 (33.8%) were female. The mean age of the patients was 51.0±6.22 years with range from 41 to 61 years. Hepatitis C seropositivity was recorded in 40 (33.06%) of the study participants during the study period. Statistically significant (p&lt;0.05) associations were observed between HCV seropositivity and age and gender of the patients. Conclusion: Hepatitis C infection is a common complication of haemodialysis. Rigorous screening of patients for Hepatitis C and separate machines for Hepatitis C patients can lead to a decrease in the burden of this disease. Pak J Physiol 2023;19(2):32–5

Seroepidemiology of Lassa virus in pregnant women in Southern Nigeria: A prospective hospital-based cohort study.

There is limited epidemiological evidence on Lassa fever in pregnant women with acute gaps on prevalence, infection incidence, and risk factors. Such evidence would facilitate the design of therapeutic and vaccine trials and the design of control programs. Our study sought to address some of these gaps by estimating the seroprevalence and seroconversion risk of Lassa fever in pregnant women. We conducted a prospective hospital-based cohort between February and December 2019 in Edo State, Southern Nigeria, enrolling pregnant women at antenatal clinic and following them up at delivery. Samples were evaluated for IgG antibodies against Lassa virus. The study demonstrates a seroprevalence of Lassa IgG antibodies of 49.6% and a seroconversion risk of 20.8%. Seropositivity was strongly correlated with rodent exposure around homes with an attributable risk proportion of 35%. Seroreversion was also seen with a seroreversion risk of 13.4%. Our study suggests that 50% of pregnant women were at risk of Lassa infection and that 35.0% of infections might be preventable by avoiding rodent exposure and conditions which facilitate infestation and the risk of human-rodent contact. While the evidence on rodent exposure is subjective and further studies are needed to provide a better understanding of the avenues of human-rodent interaction; public health measures to decrease the risk of rodent infestation and the risk of spill over events may be beneficial. With an estimated seroconversion risk of 20.8%, our study suggests an appreciable risk of contracting Lassa fever during pregnancy and while most of these seroconversions may not be new infections, given the high risk of adverse outcomes in pregnancy, it supports the need for preventative and therapeutic options against Lassa fever in pregnancy. The occurrence of seroreversion in our study suggests that the prevalence obtained in this, and other cohorts may be an underestimate of the actual proportion of women of childbearing age who present at pregnancy with prior LASV exposure. Additionally, the occurrence of both seroconversion and seroreversion in this cohort suggests that these parameters would need to be considered for the development of Lassa vaccine efficacy, effectiveness, and utility models.

Adherence to HIV Pre-Exposure Prophylaxis Testing Guidelines in the United States.

Testing guidelines for initiation of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) have been developed to ensure appropriate use of PrEP, such as among those with renal dysfunction or at high risk of seroconversion. While many studies have looked at the trends of use of PrEP in the United States, little is known about compliance with these guidelines, the quality of care of PrEP at a national level, or what provider-level factors are associated with high-quality care. We conducted a retrospective claims analysis of providers of commercially insured new users of PrEP between January 1, 2011, and December 31, 2019. Of the 4200 providers, quality of care was low, with only 6.4% having claims for ≥60% of guideline-recommended testing for their patients in the testing window for all visits. More than half of the providers did not have claims for HIV testing at initiation of PrEP and ≥40% did not for sexually transmitted infections at both initiation and follow-up visits. Even when extending the testing window, quality of care remained low. Logistic regression models found no association between provider type and high quality of care, but did find that providers with one PrEP patient were more likely to have higher quality of care than those with multiple patients for all tests [adjusted odds ratio 0.47 (95% confidence interval: 0.33-0.67)]. The study findings suggest further training and interventions, such as integrated test ordering through electronic health records, are needed to increase quality of care for PrEP and ensure appropriate monitoring of patients.

Lyme Borreliosis Serology: A Prospective Cohort Study of Forestry Service Workers in the Netherlands over 8 Years (2008 to 2016) of Follow-Up.

Blood samples from 106 forestry service workers originally included in the 200 Functional Genomics Project (Radboudumc, Nijmegen, the Netherlands) were followed for 8 years and tested annually for anti-Borrelia antibodies (ELISA and Western blot). IgG seroconversion was related to the number of tick bites in the previous year, which was obtained through annual questionnaires. The hazard ratio for Borrelia IgG seroconversion was calculated using Cox regression survival analysis and a logistic regression model, both adjusting for age, gender and smoking. Borrelia IgG seropositivity in the study population did not vary significantly between years and the average prevalence was 13.4%. Of the 27 subjects that underwent seroconversion during the study period, 22 reconverted from positive to negative. Eleven subjects seroconverted a second time. The total seroconversion rate per year (negative to positive) was 4.5%. Active smoking was associated with IgG seroconversion in the >5 tick bites group (p < 0.05). According to the two models used, the risks of IgG seroconversion in the >5 tick bites group were HR = 2.93 (p = 0.10) and OR = 3.36 (p < 0.0005). Borrelia IgG seroconversion in forestry service workers was significantly related to increasing tick bite exposure in a survival and logistic regression model adjusting for age, gender and smoking.

Analysis of Vector Shedding Following Treatment with Delandistrogene Moxeparvovec (SRP-9001), an Investigational rAAVrh74-Based Gene Therapy for Duchenne Muscular Dystrophy (DMD) (P5-8.013)

<h3>Objective:</h3> To evaluate extent and magnitude of vector shedding following delandistrogene moxeparvovec (SRP-9001) administration. <h3>Background:</h3> Delandistrogene moxeparvovec is an investigational gene transfer therapy developed to address the root cause of DMD through targeted skeletal and cardiac muscle expression of SRP-9001 dystrophin protein, which contains key functional domains of dystrophin. The hypothetical risk of seroconversion in naive individuals through exposure to vector shed from treated patients is a point to consider for healthcare providers and the Duchenne community. <h3>Design/Methods:</h3> We evaluated extent of vector shedding and clearance following a single administration of delandistrogene moxeparvovec (1.33×10¹⁴ vg/kg body weight) in ENDEAVOR (NCT04626674; Study 103; N=20), a Phase 1 study in patients with DMD. Delandistrogene moxeparvovec vector exposure in saliva, urine, and feces was quantified by droplet digital polymerase chain reaction. In a nonclinical study, we tested naive mice to determine risk of AAVrh74 seroconversion following mucosal vector exposure, with doses based on exposure levels (vector genome copies) demonstrated in nonclinical and clinical studies. Mice were exposed to AAVrh74.CMV.eGFP via optic exposure and intramuscularly. Antibody levels were measured by AAVrh74 ELISA at baseline and 4 weeks post-delivery. <h3>Results:</h3> Following treatment in ENDEAVOR, the percentage decrease in amount of vector shed was &gt;99% in saliva (n=12), urine (n=18), and feces (n=11) by Week 4. In mice, topical optical delivery of the AAVrh74 vector at relevant concentrations did not produce seropositivity or detectable vector genomes throughout tissues at doses based on clinical vector shedding levels. <h3>Conclusions:</h3> Clinical findings show that peak vector shedding occurs in the first few days after delandistrogene moxeparvovec administration and exponentially declines to insignificant levels by Week 4. In mice, seroconversion was not observed by relevant exposure route at relevant concentrations. Results suggest that the risk of seroconversion following exposure to vector shed by individuals treated with AAVrh74-based gene therapy may be very low. <b>Disclosure:</b> Jyoti Malhotra has nothing to disclose. Dr. Smith has received personal compensation for serving as an employee of Sarepta Therapeutics, Inc. Dr. Smith has stock in Sarepta Therapeutics. Sarah Lewis has received stock or an ownership interest from Sarepta. Mrs. Zhang has nothing to disclose. Mr. Asher has received personal compensation for serving as an employee of Sarepta Therapeutics. Mr. Asher has stock in Sarepta Therapeutics. Shufang Wang has received personal compensation for serving as an employee of Sarepta Therapeutics INC. Shufang Wang has received stock or an ownership interest from Sarepta Therapeutics INC. Mrs. East has received personal compensation for serving as an employee of Sarepta Therapeutics. Rachael Potter has received stock or an ownership interest from Sarepta Therapeutics. Ms. Rodino-Klapac has received personal compensation for serving as an employee of Sarepta Therapeutics, Inc.. Ms. Rodino-Klapac has received stock or an ownership interest from Sarepta Therapeutics. Ms. Rodino-Klapac has received intellectual property interests from a discovery or technology relating to health care.

Distinctive Kaposi Sarcoma-Associated Herpesvirus Serological Profile during Acute Plasmodium falciparum Malaria Episodes.

The seroprevalence of Kaposi sarcoma-associated herpesvirus (KSHV) and the incidence of endemic Kaposi sarcoma (KS) overlap with regions of malaria endemicity in sub-Saharan Africa. Multiple studies have shown an increased risk of KSHV seroconversion in children from high malaria compared to low malaria regions; however, the impact of acute episodes of Plasmodium falciparum (P. falciparum) malaria on KSHV's biphasic life cycle and lytic reactivation has not been determined. Here, we examined KSHV serological profiles and viral loads in 134 children with acute malaria and 221 healthy children from high malaria regions in Kisumu, as well as 77 healthy children from low malaria regions in Nandi. We assayed KSHV, Epstein-Barr virus (EBV), and P. falciparum malaria antibody responses in these three by multiplexed Luminex assay. We confirmed that KSHV seroprevalence was significantly associated with malaria endemicity (OR = 1.95, 1.18-3.24 95% CI, p = 0.01) with 71-77% seropositivity in high-malaria (Kisumu) compared to 28% in low-malaria (Nandi) regions. Furthermore, KSHV serological profiles during acute malaria episodes were distinct from age-matched non-malaria-infected children from the same region. Paired IgG levels also varied after malaria treatment, with significantly higher anti-ORF59 at day 0 but elevated ORF38, ORF73, and K8.1 at day 3. Acute malaria episodes is characterized by perturbation of KSHV latency in seropositive children, providing further evidence that malaria endemicity contributes to the observed increase in endemic KS incidence in sub-Saharan Africa.

Seroconversion rate after COVID-19 vaccination in patients with solid cancer: A systematic review and meta-analysis

ABSTRACT Patients with solid cancer have an increased risk of severe coronavirus disease 2019 (COVID-19) and associated mortality than the general population. This meta-analysis aimed to investigate the currently available evidence about the efficacy of COVID-19 vaccines in patients with solid cancer. We included prospective studies comparing the immunogenicity and efficacy of COVID-19 vaccines between patients with solid cancer and healthy individuals. Relative risks of seroconversion after the first and second dose of a COVID-19 vaccine were separately pooled with the use of random effects meta-analysis. Thirty studies with 11,245 subjects met the inclusion criteria. After first vaccine dose, the pooled RR of seroconversion in patients with solid cancer vs healthy individuals was 0.54 (95% CI 0.38–0.78, I 2 = 94%). After a second dose, the pooled RR of seroconversion in patients with solid cancer vs healthy controls was 0.87 (0.86–0.88, I 2 = 87%). Our review suggests that, compared with healthy individuals, COVID-19 vaccines show favorable immunogenicity and efficacy in patients with solid cancer. A second dose is associated with significantly improved seroconversion, although it is slightly lower in patients with solid cancer compared with healthy individuals.

Gender-Based Violence and Post-traumatic Stress Disorder Symptoms Predict HIV PrEP Uptake and Persistence Failure Among Transgender and Non-binary Persons Participating in a PrEP Demonstration Project in Southern California.

Gender-based violence (GBV) against transgender and nonbinary (TGNB) persons is a pervasive public health issue. GBV has been linked to mental health problems such as depression and posttraumatic stress disorder (PTSD), as well has risk for HIV seroconversion and HIV treatment nonadherence. However, the impact of GBV on HIV pre-exposure prophylaxis (PrEP) use among TGNB persons has yet to be investigated. In the current study we assessed longitudinal PrEP persistence data from dried blood spots (DBS) collected from 172 racially and ethnically diverse TGNB participants during a 48-week PrEP demonstration project in Southern California from June 2017 to September 2020. Participants were categorized into three levels of PrEP uptake and persistence based on their PrEP levels at the start and end of the study: low-low, high-low, and high-high. Individual-, social-, and structural-level variables were then entered into multinomial logistic regression models to predict levels of PrEP uptake and persistence based on hypotheses informed by syndemic and minority stress theories. The models demonstrated that experience of GBV predicted significantly lower odds of PrEP uptake and persistence and greater PTSD symptoms predicted significantly greater odds of early PrEP discontinuation. Higher levels of coping skills, already being on PrEP at baseline, and being in a steady relationship were associated with greater odds of PrEP uptake and persistence. Implications forfuture GBV research, advocacy, interventions, and much needed structural changes focused on improving the health and safety of TGNB individuals are discussed.

Severe Acute Respiratory Syndrome Coronavirus 2 Incidence and Risk Factors in a National, Community-Based Prospective Cohort of US Adults.

BackgroundProspective cohort studies of SARS-CoV-2 incidence complement case-based surveillance and cross-sectional seroprevalence surveys.MethodsWe estimated the incidence of SARS-CoV-2 infection in a national cohort of 6,738 U.S. adults, enrolled March-August 2020. Using Poisson models, we examined the association of social distancing and a composite epidemiologic risk score with seroconversion. The risk score was created using LASSO regression to identify factors predictive of seroconversion. The selected factors were household crowding, confirmed case in household, indoor dining, gathering with groups ≥ 10, and no masking in gyms/salons.ResultsAmong 4,510 individuals with ≥1 serologic test, 323 (7.3%, 95% confidence interval [CI] 6.5%-8.1%) seroconverted by January 2021. Among 3,422 participants seronegative in May-September 2020 and retested during November 2020-January 2021, 161 seroconverted over 1,646 person-years of follow-up (9.8 per 100 person-years [95%CI 8.3-11.5]). Seroincidence rate was lower among females compared to males (IRR: 0.69, 95% CI 0.50-0.94) and higher among Hispanic (IRR: 2.09, 95% CI 1.41-3.05) participants compared to White non-Hispanic. In adjusted models, participants who reported social distancing with people they did not know (IRRalways vs. never: 0.42, 95% CI 0.20-1.0) and with people they knew (IRRalways vs. never 0.64, 95%CI 0.39-1.06; IRRsometimes vs. never 0.60, 95% CI 0.38-0.96) had lower seroconversion risk. Seroconversion risk increased with epidemiologic risk score (IRRmedium vs. low 1.68, 95% CI 1.03-2.81; IRRhigh vs. low 3.49, 95% CI 2.26-5.58). Only 29% of those who seroconverted reported isolating and 19% were asked about contacts.ConclusionModifiable risk factors and poor reach of public health strategies drove SARS-CoV-2 transmission across the U.S.

Risk of seroconversion and seroreversion of antibodies to Chlamydia trachomatis pgp3 in a longitudinal cohort of children in a low trachoma prevalence district in Tanzania

BackgroundSerologic testing for chlamydial antibodies is one potential tool for trachoma monitoring. Understanding the dynamics of seroconversion and seroreversion in low endemic districts is critical for determining the value of using serology.Methodology/Principal findingsWe surveyed a random sample of 2536 children aged 1–9 years in Kongwa, Tanzania, over three years; 1719 (67.8%) participants had all three follow-ups. Surveys assessed trachomatous inflammation—follicular (TF), Chlamydia trachomatis infection, and anti-pgp3 antibodies. Mass drug administration occurred immediately after the first and second follow-up surveys. The cohort was classified into trajectories of change in serostatus, and risk factors were evaluated for seroconversion and seroreversion. We found that 86.2% of seropositives remained seropositive throughout the study, whereas 12.1% seroreverted. Seroreverters were younger (Odds Ratio [OR] = 0.88 for every one-year increase in age, 95% CI = 0.79–0.99). 84.5% of seronegatives remained seronegative, and 13.0% seroconverted. Seroconverters were also younger (OR = 0.92, 95% CI = 0.87–0.98). Seroconversion and seroreversion were not explained by indeterminate values for the intensity of antibody response. Less than 1% of the cohort had unstable changes in serostatus, mostly explained by values in the indeterminate range. TF and infection in the cohort declined over time, while seropositivity increased from 31.5% to 36.4%.Conclusions/SignificanceAntibody status is relatively stable over time. Both seroconversion and seroreversion occurred over the three years in this low endemic district, especially in younger children. Modeling seroreversion is important for accurate determination of seroconversion. The use of serology as a monitoring tool should target the younger aged children as they will most likely capture recent changes in serostatus.