Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.

BACKGROUND: Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The primary efficacy end point was a composite of Covid-19-related hospitalization or death from any cause by day 28. The primary safety end point was any adverse event. A secondary end point was a composite of a Covid-19-related medically attended visit or death from any cause by day 28. RESULTS: A total of 562 patients who underwent randomization and received at least one dose of remdesivir or placebo were included in the analyses: 279 patients in the remdesivir group and 283 in the placebo group. The mean age was 50 years, 47.9% of the patients were women, and 41.8% were Hispanic or Latinx. The most common coexisting conditions were diabetes mellitus (61.6%), obesity (55.2%), and hypertension (47.7%). Covid-19-related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P = 0.008). A total of 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a Covid-19-related medically attended visit by day 28 (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). No patients had died by day 28. Adverse events occurred in 42.3% of the patients in the remdesivir group and in 46.3% of those in the placebo group. CONCLUSIONS: Among nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo. (Funded by Gilead Sciences; PINETREE ClinicalTrials.gov number, NCT04501952; EudraCT number, 2020-003510-12.).

Latent Tuberculosis Infection Testing Practices in a Large US Integrated Healthcare System.

BACKGROUND: Tuberculosis (TB) is a public health threat, with >80% of active TB in the United States occurring due to reactivation of latent TB infection (LTBI). We may be underscreening those with high risk for LTBI and overtesting those at lower risk. A better understanding of gaps in current LTBI testing practices in relation to LTBI test positivity is needed. METHODS: This study, conducted between 1 January 2008 and 31 December 2019 at Kaiser Permanente Southern California, included individuals aged ≥18 years without a history of active TB. We examined factors associated with LTBI testing and LTBI positivity. RESULTS: Among 3 816 884 adults (52% female, 37% White, 37% Hispanic, mean age 43.5 years [standard deviation, 16.1]), 706 367 (19%) were tested for LTBI, among whom 60 393 (9%) had ≥1 positive result. Among 1 211 971 individuals who met ≥1 screening criteria for LTBI, 210 025 (17%) were tested for LTBI. Factors associated with higher adjusted odds of testing positive included male sex (1.32; 95% confidence interval, 1.30-1.35), Asian/Pacific Islander (2.78, 2.68-2.88), current smoking (1.24, 1.20-1.28), diabetes (1.13, 1.09-1.16), hepatitis B (1.45, 1.34-1.57), hepatitis C (1.54, 1.44-1.66), and birth in a country with an elevated TB rate (3.40, 3.31-3.49). Despite being risk factors for testing positive for LTBI, none of these factors were associated with higher odds of LTBI testing. CONCLUSIONS: Current LTBI testing practices may be missing individuals at high risk of LTBI. Additional work is needed to refine and implement screening guidelines that appropriately target testing for those at highest risk for LTBI.

Severe Acute Respiratory Syndrome Coronavirus 2 Delta Variant Genomic Variation Associated With Breakthrough Infection in Northern California: A Retrospective Cohort Study.

BACKGROUND: The association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic variation and breakthrough infection is not well defined among persons with Delta variant SARS-CoV-2 infection. METHODS: In a retrospective cohort, we assessed whether individual nonlineage defining mutations and overall genomic variation (including low-frequency alleles) were associated with breakthrough infection, defined as SARS-CoV-2 infection after coronavirus disease 2019 primary vaccine series. We identified all nonsynonymous single-nucleotide polymorphisms, insertions, and deletions in SARS-CoV-2 genomes with ≥5% allelic frequency and population frequency of ≥5% and ≤95%. Using Poisson regression, we assessed the association with breakthrough infection for each individual mutation and a viral genomic risk score. RESULTS: Thirty-six mutations met our inclusion criteria. Among 12 744 persons infected with Delta variant SARS-CoV-2, 5949 (47%) were vaccinated and 6795 (53%) were unvaccinated. Viruses with a viral genomic risk score in the highest quintile were 9% more likely to be associated with breakthrough infection than viruses in the lowest quintile, but including the risk score improved overall predictive model performance (measured by C statistic) by only +0.0006. CONCLUSIONS: Genomic variation within SARS-CoV-2 Delta variant was weakly associated with breakthrough infection, but several potential nonlineage defining mutations were identified that might contribute to immune evasion by SARS-CoV-2.

Influenza Vaccination Uptake and Associated Factors Among Adults With and Without Human Immunodeficiency Virus in a Large, Integrated Healthcare System.

BACKGROUND: Influenza vaccination is recommended for adults regardless of human immunodeficiency virus (HIV) status. There may be facilitators or barriers to vaccinating people with HIV (PWH) that differ from people without HIV (PWoH). We sought to describe the uptake of influenza vaccination by HIV status and identify factors associated with vaccination. METHODS: We abstracted data from the electronic health records of PWH and PWoH in Kaiser Permanente Northern California during 6 influenza seasons (2013-2018). We determined vaccination uptake and used Poisson regression models to evaluate factors associated with vaccination in PWH and PWoH. RESULTS: 9272 PWH and 194 393 PWoH matched by age, sex, and race/ethnicity were included (mean age: 48 vs 49 years; men: 91% vs 90%; White race: 53% for both groups). PWH were more likely to receive the influenza vaccine (65-69% across years for PWH and 37-41% for PWoH) with an adjusted risk ratio for all years of 1.48 (95% CI: 1.46-1.50). For PWH, lower vaccination uptake was associated with several factors that suggested more complex health needs, such as lower CD4 cell counts, higher HIV viral loads, prior depression diagnoses, having Medicare insurance, and having a higher number of comorbidities. Associations with vaccination uptake were attenuated in PWH, compared with PWoH, for smoking, alcohol, and demographic factors. CONCLUSIONS: PWH had an almost 50% higher uptake of influenza vaccination than PWoH, possibly reflecting greater engagement with the healthcare system. We also found that PWH with more complex health needs had reduced vaccination uptake. Findings may inform outreach strategies to increase influenza vaccination in PWH.

Human Immunodeficiency Virus Status, Tenofovir Exposure, and the Risk of Poor Coronavirus Disease 19 Outcomes: Real-World Analysis From 6 United States Cohorts Before Vaccine Rollout.

BACKGROUND: People with human immunodeficiency virus (HIV) (PWH) may be at increased risk for severe coronavirus disease 2019 (COVID-19) outcomes. We examined HIV status and COVID-19 severity, and whether tenofovir, used by PWH for HIV treatment and people without HIV (PWoH) for HIV prevention, was associated with protection. METHODS: Within 6 cohorts of PWH and PWoH in the United States, we compared the 90-day risk of any hospitalization, COVID-19 hospitalization, and mechanical ventilation or death by HIV status and by prior exposure to tenofovir, among those with severe acute respiratory syndrome coronavirus 2 infection between 1 March and 30 November 2020. Adjusted risk ratios (aRRs) were estimated by targeted maximum likelihood estimation, with adjustment for demographics, cohort, smoking, body mass index, Charlson comorbidity index, calendar period of first infection, and CD4 cell counts and HIV RNA levels (in PWH only). RESULTS: Among PWH (n = 1785), 15% were hospitalized for COVID-19 and 5% received mechanical ventilation or died, compared with 6% and 2%, respectively, for PWoH (n = 189 351). Outcome prevalence was lower for PWH and PWoH with prior tenofovir use. In adjusted analyses, PWH were at increased risk compared with PWoH for any hospitalization (aRR, 1.31 [95% confidence interval, 1.20-1.44]), COVID-19 hospitalizations (1.29 [1.15-1.45]), and mechanical ventilation or death (1.51 [1.19-1.92]). Prior tenofovir use was associated with reduced hospitalizations among PWH (aRR, 0.85 [95% confidence interval, .73-.99]) and PWoH (0.71 [.62-.81]). CONCLUSIONS: Before COVID-19 vaccine availability, PWH were at greater risk for severe outcomes than PWoH. Tenofovir was associated with a significant reduction in clinical events for both PWH and PWoH.

An Atypical Presentation of Mpox Transmitted Between Transgender Men Through Oral Sex.

ABSTRACT: The current multicountry outbreak of mpox in 2022 is the first occurrence of widespread transmission in nonendemic countries. Prior cases in the United States involved exposure through foreign travel or direct contact with infected rodents. Reports of the current outbreak have predominately described spread through sexual encounters between cis-gender men who have sex with men. We report a unique case of mpox in which the transmission occurred through oral sex between 2 transgender men, with a short incubation period and progressive asynchronous emergence of lesions. Continued analysis of transmission routes and awareness will improve timely prevention, diagnosis and treatment.

Patient-Reported Barriers to Treatment Initiation and Completion for Latent Tuberculosis Infection Among Patients Within a Large Integrated Health Care System in Southern California.

OBJECTIVE: More than 80% of active tuberculosis in the United States is due to reactivation of latent tuberculosis infection (LTBI), which can be prevented via screening and treatment. Treatment initiation and completion rates are low for patients with LTBI in the United States, and the barriers to successful treatment are poorly understood. DESIGN: We conducted semistructured qualitative interviews with 38 patients who were prescribed LTBI treatment (9 months isoniazid, 6 months rifampin, or 3 months rifamycin-isoniazid short-course combinations). We used purposeful sampling employing a maximum variation approach to obtain diverse perspectives of patients who did not initiate treatment, who did not complete treatment, and who completed treatment (n = 14, n = 16, and n = 8, respectively). Patients were asked about LTBI knowledge, experience regarding treatment, interactions with providers, and barriers they faced. Using a team coding model (2 coders/analysts), we developed deductively derived (a priori) codes based on our central research questions and inductively derived codes that emerged directly from the data. Analysis of our coding categories and relationships generated a hierarchy of key themes and subthemes. SETTING: Kaiser Permanente Southern California. PARTICIPANTS: Individuals 18 years or older who received a diagnosis of LTBI and prescribed treatment. MAIN OUTCOME MEASURES: LTBI knowledge, attitudes toward LTBI, attitudes toward LTBI treatment, attitudes toward providers, and explanation of barriers. RESULTS: Most patients reported having limited knowledge of LTBI. In addition to the duration of treatment, barriers to initiation and completion included perceived lack of support, uncomfortable side effects, and pervasive minimization of the positive impact of treatment on their health. Many patients felt there was little incentive to overcome barriers. CONCLUSIONS: Overall, patient experience with LTBI treatment initiation and completion could be improved with patient-centered treatment and more frequent follow-ups.

Rationale and design of the pragmatic randomized trial of icosapent ethyl for high cardiovascular risk adults (MITIGATE).

OBJECTIVE: The MITIGATE study aims to evaluate the real-world clinical effectiveness of pre-treatment with icosapent ethyl (IPE), compared with usual care, on laboratory-confirmed viral upper respiratory infection (URI)-related morbidity and mortality in adults with established atherosclerotic cardiovascular disease (ASCVD). BACKGROUND: IPE is a highly purified and stable omega-3 fatty acid prescription medication that is approved for cardiovascular risk reduction in high-risk adults on statin therapy with elevated triglycerides. Preclinical data and clinical observations suggest that IPE may have pleiotropic effects including antiviral and anti-inflammatory properties that may prevent or reduce the downstream sequelae and cardiopulmonary consequences of viral URIs. METHODS: MITIGATE is a virtual, electronic health record-based, open-label, randomized, pragmatic clinical trial enrolling ∼16,500 participants within Kaiser Permanente Northern California - a fully integrated and learning health care delivery system with 21 hospitals and >255 ambulatory clinics serving ∼4.5 million members. Adults ≥50 years with established ASCVD and no prior history of coronavirus disease 2019 (COVID-19) will be prospectively identified and pre-randomized in a 1:10 allocation ratio (∼ 1,500 IPE: ∼15,000 usual care) stratified by age and previous respiratory health status to the intervention (IPE 2 grams by mouth twice daily with meals) vs the control group (usual care) for a minimum follow-up duration of 6 months. The co-primary endpoints are moderate-to-severe laboratory-confirmed viral URI and worst clinical status due to a viral URI at any point in time. CONCLUSION: The MITIGATE study will inform clinical practice by providing evidence on the real-world clinical effectiveness of pretreatment with IPE to prevent and/or reduce the sequelae of laboratory-confirmed viral URIs in a high-risk cohort of patients with established ASCVD.

Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization.

BACKGROUND: Obesity, race/ethnicity, and other correlated characteristics have emerged as high-profile risk factors for adverse coronavirus disease 2019 (COVID-19)-associated outcomes, yet studies have not adequately disentangled their effects. OBJECTIVE: To determine the adjusted effect of body mass index (BMI), associated comorbidities, time, neighborhood-level sociodemographic factors, and other factors on risk for death due to COVID-19. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Southern California, a large integrated health care organization. PATIENTS: Kaiser Permanente Southern California members diagnosed with COVID-19 from 13 February to 2 May 2020. MEASUREMENTS: Multivariable Poisson regression estimated the adjusted effect of BMI and other factors on risk for death at 21 days; models were also stratified by age and sex. RESULTS: Among 6916 patients with COVID-19, there was a J-shaped association between BMI and risk for death, even after adjustment for obesity-related comorbidities. Compared with patients with a BMI of 18.5 to 24 kg/m2, those with BMIs of 40 to 44 kg/m2 and greater than 45 kg/m2 had relative risks of 2.68 (95% CI, 1.43 to 5.04) and 4.18 (CI, 2.12 to 8.26), respectively. This risk was most striking among those aged 60 years or younger and men. Increased risk for death associated with Black or Latino race/ethnicity or other sociodemographic characteristics was not detected. LIMITATION: Deaths occurring outside a health care setting and not captured in membership files may have been missed. CONCLUSION: Obesity plays a profound role in risk for death from COVID-19, particularly in male patients and younger populations. Our capitated system with more equalized health care access may explain the absence of effect of racial/ethnic and socioeconomic disparities on death. Our data highlight the leading role of severe obesity over correlated risk factors, providing a target for early intervention. PRIMARY FUNDING SOURCE: Roche-Genentech.

Comparison of msp genotyping and a 24 SNP molecular assay for differentiating Plasmodium falciparum recrudescence from reinfection.

BACKGROUND: Current World Health Organization guidelines for conducting anti-malarial drug efficacy clinical trials recommend genotyping Plasmodium falciparum genes msp1 and msp2 to distinguish recrudescence from reinfection. A more recently developed potential alternative to this method is a molecular genotyping assay based on a panel of 24 single nucleotide polymorphism (SNP) markers. METHODS: Performance parameters of these two genotyping methods were compared using data from two recently completed drug efficacy trials. Blood samples from two anti-malarial therapeutic trials were analysed by both msp genotyping and the 24 SNP assay. Additionally, to conserve time and resources, the statistical program R was used to select the most informative SNPs for a set of unrelated Malawian samples to develop a truncated SNP-based assay for the region surrounding Blantyre, Malawi. The ability of this truncated assay to distinguish reinfection from recrudescence when compared to the full 24 SNP assay was then analysed using data from the therapeutic trials. RESULTS: A total of 360 samples were analysed; 66 for concordance of msp and SNP barcoding methodologies, and 294 for assessing the most informative of the 24 SNP markers. SNP genotyping performed comparably to msp genotyping, with only one case of disagreement among the 50 interpretable results, where the SNP assay identified the sample as reinfection and the msp typing as recrudescence. Furthermore, SNP typing was more robust; only 6% of samples were uninterpretable by SNP typing, compared to 19.7% when msp genotyping was used. For discriminating reinfection from recrudescence, a truncated 6 SNP assay was found to perform at 95.1% the accuracy of the full 24 SNP bar code. CONCLUSIONS: The use of SNP analysis has similar sensitivity to the standard msp genotyping in determining recrudescence from reinfection. Although more expensive, SNP typing is faster and less work intensive. Limiting the assay to those SNPs most informative in the geographical region of interest may further decrease the workload and the cost, making this technique a feasible and affordable alternative in drug efficacy trials.

Erectile Dysfunction Medication Prescription and Condomless Intercourse in HIV-Infected Men Who have Sex with Men in the United States.

Using nationally representative data, we assessed the prevalence of erectile dysfunction medication (EDM) prescription, and its association with insertive condomless anal intercourse (CAI) with an HIV-serodiscordant partner among sexually-active HIV-infected men who have sex with men (MSM) receiving medical care in the United States. Overall, 14 % (95 % CI 12-16) were prescribed EDM and 21 % (95 % CI 19-23) engaged in serodiscordant CAI. MSM who were prescribed EDM were more likely to engage in insertive CAI with a serodiscordant casual partner than those not prescribed EDM after adjusting for illicit drug use before or during sex (adjusted prevalence ratio = 1.38; 95 % CI 1.01-1.88). We found no association with main partners. Only 40 % (95 % CI 36-44) of MSM prescribed EDM received risk-reduction counseling from healthcare professionals. Risk-reduction counseling should be provided at least annually to all HIV-infected persons as recommended, especially at the time of EDM prescription.

Prevalence of Internalized HIV-Related Stigma Among HIV-Infected Adults in Care, United States, 2011-2013.

HIV-infected U.S. adults have reported internalized HIV-related stigma; however, the national prevalence of stigma is unknown. We sought to determine HIV-related stigma prevalence among adults in care, describe which socio-demographic groups bear the greatest stigma burden, and assess the association between stigma and sustained HIV viral suppression. The Medical Monitoring Project measures characteristics of U.S. HIV-infected adults receiving care using a national probability sample. We used weighted data collected from June 2011 to May 2014 and assessed self-reported internalized stigma based on agreement with six statements. Overall, 79.1% endorsed ≥1 HIV-related stigma statements (n = 13,841). The average stigma score was 2.4 (out of a possible high score of six). White males had the lowest stigma scores while Hispanic/Latina females and transgender persons who were multiracial or other race had the highest. Although stigma was associated with viral suppression, it was no longer associated after adjusting for age. Stigma was common among HIV-infected adults in care. Results suggest individual and community stigma interventions may be needed, particularly among those who are <50 years old or Hispanic/Latino. Stigma was not independently associated with viral suppression; however, this sample was limited to adults in care. Examining HIV-infected persons not in care may elucidate stigma's association with viral suppression.

Challenges in the Evaluation of Interventions to Improve Engagement Along the HIV Care Continuum in the United States: A Systematic Review.

In the United States (US), there are high levels of disengagement along the HIV care continuum. We sought to characterize the heterogeneity in research studies and interventions to improve care engagement among people living with diagnosed HIV infection. We performed a systematic literature search for interventions to improve HIV linkage to care, retention in care, reengagement in care and adherence to antiretroviral therapy (ART) in the US published from 2007-mid 2015. Study designs and outcomes were allowed to vary in included studies. We grouped interventions into categories, target populations, and whether results were significantly improved. We identified 152 studies, 7 (5%) linkage studies, 33 (22%) retention studies, 4 (3%) reengagement studies, and 117 (77%) adherence studies. 'Linkage' studies utilized 11 different outcome definitions, while 'retention' studies utilized 39, with very little consistency in effect measurements. The majority (59%) of studies reported significantly improved outcomes, but this proportion and corresponding effect sizes varied substantially across study categories. This review highlights a paucity of assessments of linkage and reengagement interventions; limited generalizability of results; and substantial heterogeneity in intervention types, outcome definitions, and effect measures. In order to make strides against the HIV epidemic in the US, care continuum research must be improved and benchmarked against an integrated, comprehensive framework.

Ryan White HIV/AIDS Program Assistance and HIV Treatment Outcomes.

BACKGROUND: The Ryan White HIV/AIDS Program (RWHAP) provides persons infected with human immunodeficiency virus (HIV) with services not covered by other healthcare payer types. Limited data exist to inform policy decisions about the most appropriate role for RWHAP under the Patient Protection and Affordable Care Act (ACA). METHODS: We assessed associations between RWHAP assistance and antiretroviral therapy (ART) prescription and viral suppression. We used data from the Medical Monitoring Project, a surveillance system assessing characteristics of HIV-infected adults receiving medical care in the United States. Interview and medical record data were collected in 2009-2013 from 18 095 patients. RESULTS: Nearly 41% of patients had RWHAP assistance; 15% relied solely on RWHAP assistance for HIV care. Overall, 91% were prescribed ART, and 75% were virally suppressed. Uninsured patients receiving RWHAP assistance were significantly more likely to be prescribed ART (52% vs 94%; P < .01) and virally suppressed (39% vs 77%; P < .01) than uninsured patients without RWHAP assistance. Patients with private insurance and Medicaid were 6% and 7% less likely, respectively, to be prescribed ART than those with RWHAP only (P < .01). Those with private insurance and Medicaid were 5% and 12% less likely, respectively, to be virally suppressed (P ≤ .02) than those with RWHAP only. Patients whose private or Medicaid coverage was supplemented by RWHAP were more likely to be prescribed ART and virally suppressed than those without RWHAP supplementation (P ≤ .01). CONCLUSIONS: Uninsured and underinsured HIV-infected persons receiving RWHAP assistance were more likely to be prescribed ART and virally suppressed than those with other types of healthcare coverage.

Qualifications, Demographics, Satisfaction, and Future Capacity of the HIV Care Provider Workforce in the United States, 2013-2014.

BACKGROUND: The human immunodeficiency virus (HIV)-infected population in the United States is increasing by about 30 000 annually (new infections minus deaths). With improvements in diagnosis and engagement in care, additional qualified HIV care providers may be needed. METHODS: We surveyed a probability sample of 2023 US HIV care providers in 2013-2014, including those at Ryan White HIV/AIDS Program (RWHAP)-funded facilities and in private practices. We estimated future patient care capacity by comparing counts of providers entering and planning to leave practice within 5 years, and the number of patients under their care. RESULTS: Of surveyed providers, 1234 responded (adjusted response rate, 64%): 63% were white, 11% black, 11% Hispanic, and 16% other race/ethnicity; 37% were satisfied/very satisfied with salary/reimbursement, and 33% were satisfied/very satisfied with administrative time. Compared with providers in private practice, more providers at RWHAP-funded facilities were HIV specialists (71% vs 43%; P < .0001) and planned to leave HIV practice within 5 years (11% vs 4%; P = .0004). An estimated 190 more full-time equivalent providers (defined as 40 HIV clinical care hours per week) entered practice in the past 5 years than are expected to leave in the next 5 years. If these rates continue, by 2019 patient care capacity will increase by 65 000, compared with an increased requirement of at least 100 000. CONCLUSIONS: Projected workforce growth by 2019 will not accommodate the increased number of HIV-infected persons requiring care. RWHAP-funded facilities may face attrition of highly qualified providers. Dissatisfaction with salary/reimbursement and administrative burden is substantial, and black and Hispanic providers are underrepresented relative to HIV patients.

Cardiovascular Disease Risk Prediction in the HIV Outpatient Study.

BACKGROUND: Cardiovascular disease (CVD) risk prediction tools are often applied to populations beyond those in which they were designed when validated tools for specific subpopulations are unavailable. METHODS: Using data from 2283 human immunodeficiency virus (HIV)-infected adults aged ≥18 years, who were active in the HIV Outpatient Study (HOPS), we assessed performance of 3 commonly used CVD prediction models developed for general populations: Framingham general cardiovascular Risk Score (FRS), American College of Cardiology/American Heart Association Pooled Cohort equations (PCEs), and Systematic COronary Risk Evaluation (SCORE) high-risk equation, and 1 model developed in HIV-infected persons: the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study equation. C-statistics assessed model discrimination and the ratio of expected to observed events (E/O) and Hosmer-Lemeshow χ2 P value assessed calibration. RESULTS: From January 2002 through September 2013, 195 (8.5%) HOPS participants experienced an incident CVD event in 15 056 person-years. The FRS demonstrated moderate discrimination and was well calibrated (C-statistic: 0.66, E/O: 1.01, P = .89). The PCE and D:A:D risk equations demonstrated good discrimination but were less well calibrated (C-statistics: 0.71 and 0.72 and E/O: 0.88 and 0.80, respectively; P < .001 for both), whereas SCORE performed poorly (C-statistic: 0.59, E/O: 1.72; P = .48). CONCLUSIONS: Only the FRS accurately estimated risk of CVD events, while PCE and D:A:D underestimated risk. Although these models could potentially be used to rank US HIV-infected individuals at higher or lower risk for CVD, the models may fail to identify substantial numbers of HIV-infected persons with elevated CVD risk who could potentially benefit from additional medical treatment.

Impact of Sulfadoxine-Pyrimethamine Resistance on Effectiveness of Intermittent Preventive Therapy for Malaria in Pregnancy at Clearing Infections and Preventing Low Birth Weight.

BACKGROUND: Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of intermittent preventive therapy in pregnancy (IPTp) with SP is crucial. METHODS: Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus-uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted. RESULTS: Among 1222 parasitemic pregnant women, overall polymerase chain reaction-uncorrected and -corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI], .69-.88; P < .001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI, .67-.97; P = .02). CONCLUSIONS: The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy.

Delayed entry into HIV medical care in a nationally representative sample of HIV-infected adults receiving medical care in the USA.

Before widespread antiretroviral therapy (ART), an estimated 17% of people delayed HIV care. We report national estimates of the prevalence and factors associated with delayed care entry in the contemporary ART era. We used Medical Monitoring Project data collected from June 2009 through May 2011 for 1425 persons diagnosed with HIV from May 2004 to April 2009 who initiated care within 12 months. We defined delayed care as entry >three months from diagnosis. Adjusted prevalence ratios (aPRs) were calculated to identify risk factors associated with delayed care. In this nationally representative sample of HIV-infected adults receiving medical care, 7.0% (95% confidence interval [CI]: 5.3-8.8) delayed care after diagnosis. Black race was associated with a lower likelihood of delay than white race (aPR 0.38). Men who have sex with women versus women who have sex with men (aPR 1.86) and persons required to take an HIV test versus recommended by a provider (aPR 2.52) were more likely to delay. Among those who delayed 48% reported a personal factor as the primary reason. Among persons initially diagnosed with HIV (non-AIDS), those who delayed care were twice as likely (aPR 2.08) to develop AIDS as of May 2011. Compared to the pre-ART era, there was a nearly 60% reduction in delayed care entry. Although relatively few HIV patients delayed care entry, certain groups may have an increased risk. Focus on linkage to care among persons who are required to take an HIV test may further reduce delayed care entry.

Cigarette smoking prevalence among adults with HIV compared with the general adult population in the United States: cross-sectional surveys.

BACKGROUND: The negative health effects of cigarette smoking and HIV infection are synergistic. OBJECTIVE: To compare the prevalence of current cigarette smoking and smoking cessation between adults with HIV receiving medical care and adults in the general population. DESIGN: Nationally representative cross-sectional surveys. SETTING: United States. PATIENTS: 4217 adults with HIV who participated in the Medical Monitoring Project and 27 731 U.S. adults who participated in the National Health Interview Survey in 2009. MEASUREMENTS: The main exposure was cigarette smoking. The outcome measures were weighted prevalence of cigarette smoking and quit ratio (ratio of former smokers to the sum of former and current smokers). RESULTS: Of the estimated 419 945 adults with HIV receiving medical care, 42.4% (95% CI, 39.7% to 45.1%) were current cigarette smokers, 20.3% (CI, 18.6% to 22.1%) were former smokers, and 37.3% (CI, 34.9% to 39.6%) had never smoked. Compared with the U.S. adult population, in which an estimated 20.6% of adults smoked cigarettes in 2009, adults with HIV were nearly twice as likely to smoke (adjusted prevalence difference, 17.0 percentage points [CI, 14.0 to 20.1 percentage points]) but were less likely to quit smoking (quit ratio, 32.4% vs. 51.7%). Among adults with HIV, factors independently associated with greater smoking prevalence were older age, non-Hispanic white or non-Hispanic black race, lower educational level, poverty, homelessness, incarceration, substance use, binge alcohol use, depression, and not achieving a suppressed HIV viral load. LIMITATION: Cross-sectional design with some generalizability limitations. CONCLUSION: Adults with HIV were more likely to smoke and less likely to quit smoking than the general adult population. Tobacco screening and cessation strategies are important considerations as part of routine HIV care.