Search

Background Isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) reduces nosocomial transmission risk. Efficient evaluation of PUIs is needed to preserve scarce healthcare resources. We describe the development, implementation, and outcomes of an inpatient diagnostic algorithm and clinical decision support system (CDSS) to evaluate PUIs. Methods We conducted a pre-post study of CORAL (COvid Risk cALculator), a CDSS that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to infectious diseases (ID) physician review. Before CORAL, ID physicians reviewed all PUI records to guide workup and precautions. After CORAL, frontline clinicians evaluated PUIs directly using CORAL. We compared pre- and post-CORAL frequency of repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs), time from NAAT result to PUI status discontinuation, total duration of PUI status, and ID physician work hours, using linear and logistic regression, adjusted for COVID-19 incidence. Results Fewer PUIs underwent repeated testing after an initial negative NAAT after CORAL than before CORAL (54% vs 67%, respectively; adjusted odd ratio, 0.53 [95% confidence interval, .44–.63]; P Conclusions CORAL is an efficient and effective CDSS to guide frontline clinicians through the diagnostic evaluation of PUIs and safe discontinuation of precautions.

Background Of new HIV infections in the US, 20% occur among young men who have sex with men (YMSM, ages 13–24), but >50% of YMSM with HIV are unaware of their status. Using Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) data, we projected the clinical benefit and cost-effectiveness of frequent HIV screening among high-risk YMSM from age 15. Methods Using a mathematical simulation, we examined 3 screening strategies: Yearly, 6-monthly, and 3-monthly, each in addition to the Status quo (SQ, 0.7–10.3% screened/year, stratified by age). We used published data (YMSM-specific when available) including: HIV incidences (0.91–6.41/100PY); screen acceptance (80%), linkage-to-care/antiretroviral therapy (ART) initiation (76%), HIV transmission (0.3–86.1/100PY, by HIV RNA), monthly ART costs ($2290-$3780), and HIV per-screen costs ($38). Projected outcomes included CD4 count at diagnosis, primary HIV transmissions from ages 15–30, quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year saved [QALY]; threshold ≤$100 000/QALY). Results Compared to SQ, all strategies increased projected CD4 at diagnosis (296 to 477–515 cells/µL) and quality-adjusted life expectancy from age 15 (44.4 to 48.3–48.7 years) among YMSM acquiring HIV. Compared to SQ, all strategies increased discounted lifetime cost for the entire population ($170 800 to $178 100-$185 000/person). Screening 3-monthly was cost-effective (ICER: $4500/QALY) compared to SQ and reduced primary transmissions through age 30 by 40%. Results were most sensitive to transmission rates; excluding the impact of transmissions, screening Yearly was ≤$100 000/QALY (ICER: $70 900/QALY). Conclusions For high-risk YMSM in the US, HIV screening 3-monthly compared to less frequent screening will improve clinical outcomes and be cost-effective.

Background The World Health Organization (WHO) human immunodeficiency virus (HIV) diagnostic strategy requires 6 rapid diagnostic tests (RDTs). Point-of-care nucleic acid tests (POC NATs) are costlier, less sensitive, but more specific than RDTs. Methods We simulated a 1-time screening process in Côte d’Ivoire (CI; undiagnosed prevalence: 1.8%), comparing WHO- and CI-recommended RDT-based strategies (RDT-WHO, RDT-CI) and an alternative: POC NAT to resolve RDT discordancy (NAT-Resolve). Costs included assays (RDT: $1.47; POC NAT: $27.92), antiretroviral therapy ($6–$22/month), and HIV care ($27–$38/month). We modeled 2 sensitivity/specificity scenarios: high-performing (RDT: 99.9%/99.1%; POC NAT: 95.0%/100.0%) and low-performing (RDT: 91.1%/82.9%; POC NAT: 93.3%/99.5%). Outcomes included true-positive (TP), false-positive (FP), true-negative (TN), or false-negative (FN) results; life expectancy; costs; and incremental cost-effectiveness ratios (ICERs: $/year of life saved [YLS]; threshold ≤$1720/YLS [per-capita gross domestic product]). Results Model-projected impacts of misdiagnoses were 4.4 years lost (FN vs TP; range, 3.0–13.0 years) and a $5800 lifetime cost increase (FP vs TN; range, $590–$14 680). In the high-performing scenario, misdiagnoses/10 000 000 tested were lowest for NAT-Resolve vs RDT-based strategies (FN: 409 vs 413–429; FP: 14 vs 21–28). Strategies had similar life expectancy (228 months) and lifetime costs ($220/person) among all tested; ICERs were $3450/YLS (RDT-CI vs RDT-WHO) and $120 910/YLS (NAT-Resolve vs RDT-CI). In the low-performing scenario, misdiagnoses were higher (FN: 22 845–30 357; FP: 83 724–112 702) and NAT-Resolve was cost-saving. Conclusions We projected substantial clinical and economic impacts of misdiagnoses. Using POC NAT to resolve RDT discordancy generated the fewest misdiagnoses and was not cost-effective in high-performing scenarios, but may be an important adjunct to existing RDT-based strategies in low-performing scenarios.

Background Reports of SARS-CoV2 infection have focused on pregnant women hospitalized due to moderate to severe COVID-19 disease or asymptomatic women diagnosed through universal screening at the time of obstetric admission. Many pregnant women who have symptomatic SARS-CoV2 infection may not meet criteria for hospitalization; however, whether and how these women can be managed safely in outpatient setting is not well described. Objective We sought to describe the time to symptom and viral clearance and to identify predictors of hospitalization in order to better understand the safety of monitoring pregnant patients with symptomatic COVID-19 in the outpatient setting. Study Design We performed a retrospective cohort study of pregnant patients with symptomatic, confirmed COVID-19 illness at a large academic medical center. Patients had systematic telehealth follow up by a clinician team to assess for symptoms, provide virtual prenatal care, and arrange in-person visits when appropriate in a dedicated outpatient center. Data was collected via chart abstraction. Results Of 180 pregnant patients presenting with symptoms and undergoing RT-PCR testing, 67 patients with confirmed COVID-19 infection were identified during the study period. Nineteen (28%) required acute care given worsening of COVID-19 symptoms, and 95% of these were directed to this acute care setting due to symptom severity telehealth evaluation. Nine women (13%) were admitted to the hospital given worsening symptoms, 3 required ICU care, 2 required ventilatory support, and 2 required delivery. Women with the presenting symptoms of fever, cough, shortness of breath, chest pain, or nausea and vomiting were more likely to require admission. The median duration from initial positive test to RT-PCR viral clearance was 26 days. Disease progression, time to viral clearance and duration of symptoms did not vary significantly by trimester of infection. Conclusions Management of the majority of pregnant women with symptomatic COVID-19 illness can be accomplished in the outpatient setting with intensive and protocol-driven monitoring for symptom progression.

Background We projected the clinical and economic impact of alternative testing strategies on coronavirus disease 2019 (COVID-19) incidence and mortality in Massachusetts using a microsimulation model. Methods We compared 4 testing strategies: (1) hospitalized: polymerase chain reaction (PCR) testing only for patients with severe/critical symptoms warranting hospitalization; (2) symptomatic: PCR for any COVID-19–consistent symptoms, with self-isolation if positive; (3) symptomatic + asymptomatic once: symptomatic and 1-time PCR for the entire population; and (4) symptomatic + asymptomatic monthly: symptomatic with monthly retesting for the entire population. We examined effective reproduction numbers (Re = 0.9–2.0) at which policy conclusions would change. We assumed homogeneous mixing among the Massachusetts population (excluding those residing in long-term care facilities). We used published data on disease progression and mortality, transmission, PCR sensitivity/specificity (70%/100%), and costs. Model-projected outcomes included infections, deaths, tests performed, hospital-days, and costs over 180 days, as well as incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year [QALY]). Results At Re = 0.9, symptomatic + asymptomatic monthly vs hospitalized resulted in a 64% reduction in infections and a 46% reduction in deaths, but required >66-fold more tests/day with 5-fold higher costs. Symptomatic + asymptomatic monthly had an ICER Conclusions Testing people with any COVID-19–consistent symptoms would be cost-saving compared to testing only those whose symptoms warrant hospital care. Expanding PCR testing to asymptomatic people would decrease infections, deaths, and hospitalizations. Despite modest sensitivity, low-cost, repeat screening of the entire population could be cost-effective in all epidemic settings.

Background Cardiovascular disease (CVD) is an increasing cause of morbidity among persons living with human immunodeficiency virus (HIV; PLWH). We projected cumulative CVD risk in PLWH in care compared to the US general population and persons HIV-uninfected, but at high risk for HIV. Methods We used a mathematical model to project cumulative CVD incidence. We simulated a male and female cohort for each of 3 populations: US general population; HIV-uninfected, at high risk for HIV; and PLWH. We incorporated the higher smoking prevalence and increased CVD risk due to smoking into the HIV-infected and HIV-uninfected, at high risk for HIV populations. We incorporated HIV-attributable CVD risk, independent of smoking. Results For men, life expectancy ranged from 70.2 to 77.5 years and for women from 67.0 to 81.1 years (PLWH, US general population). Without antiretroviral therapy, lifetime CVD risk for HIV-infected males and females was 12.9% and 9.0%. For males, by age 60, cumulative CVD incidence was estimated at 20.5% in PLWH in care, 14.6% in HIV-uninfected high-risk persons, and 12.8% in the US general population. For females, cumulative CVD incidence was projected to be 13.8% in PLWH in care, 9.7% for high-risk HIV-uninfected persons, and 9.4% in the US general population. Lifetime CVD risk was 64.8% for HIV-infected males compared to 54.8% for males in the US general population, but similar among females. Conclusions CVD risks should be a part of treatment evaluation among PLWH. CVD prevention strategies could offer important health benefits for PLWH and should be evaluated.

Background The NEVEREST-3 (South Africa) and MONOD-ANRS-12206 (Côte d’Ivoire, Burkina Faso) randomized trials found that switching to efavirenz (EFV) in human immunodeficiency virus–infected children >3 years old who were virologically suppressed by ritonavir-boosted lopinavir (LPV/r) was noninferior to continuing o LPV/r. We evaluated the cost-effectiveness of this strategy using the Cost-Effectiveness of Preventing AIDS Complications–Pediatric model. Methods We examined 3 strategies in South African children aged ≥3 years who were virologically suppressed by LPV/r: (1) continued LPV/r, even in case of virologic failure, without second-line regimens; continued on LPV/r with second-line option after observed virologic failure; and preemptive switch to EFV-based antiretroviral therapy (ART), with return to LPV/r after observed virologic failure. We derived data on 24-week suppression (, Using the Cost-Effectiveness of Preventing AIDS Complications–Pediatric model to project clinical outcomes, costs, and cost-effectiveness, we show that preemptively switching to efavirenz in virologically suppressed children >3 years old receiving ritonavir-boosted lopinavir (LPV/r) is cost saving compared with continued LPV/r.

Background Diagnosis of human immunodeficiency virus (HIV) infection during early infancy (commonly known as "early infant HIV diagnosis" [EID]) followed by prompt initiation of antiretroviral therapy dramatically reduces mortality. EID testing is recommended at 6 weeks of age, but many infant infections are missed. Design/methods We simulated 4 EID testing strategies for HIV-exposed infants in South Africa: no EID (diagnosis only after illness; hereafter, "no EID"), testing once (at birth alone or at 6 weeks of age alone; hereafter, "birth alone" and "6 weeks alone," respectively), and testing twice (at birth and 6 weeks of age; hereafter "birth and 6 weeks"). We calculated incremental cost-effectiveness ratios (ICERs), using discounted costs and life expectancies for all HIV-exposed (infected and uninfected) infants. Results In the base case (guideline-concordant care), the no EID strategy produced a life expectancy of 21.1 years (in the HIV-infected group) and 61.1 years (in the HIV-exposed group); lifetime cost averaged $1430/HIV-exposed infant. The birth and 6 weeks strategy maximized life expectancy (26.5 years in the HIV-infected group and 61.4 years in the HIV-exposed group), costing $1840/infant tested. The ICER of the 6 weeks alone strategy versus the no EID strategy was $1250/year of life saved (19% of South Africa's per capita gross domestic product); the ICER for the birth and 6 weeks strategy versus the 6 weeks alone strategy was $2900/year of life saved (45% of South Africa's per capita gross domestic product). Increasing the proportion of caregivers who receive test results and the linkage of HIV-positive infants to antiretroviral therapy with the 6 weeks alone strategy improved survival more than adding a second test. Conclusions EID at birth and 6 weeks improves outcomes and is cost-effective, compared with EID at 6 weeks alone. If scale-up costs are comparable, programs should add birth testing after strengthening 6-week testing programs.

Background Adolescents and young adults (AYA) with HIV experience worse health outcomes than adults with HIV in the United States. Little is known about AYA patterns of utilization of costly healthcare resources. Methods We estimated utilization of outpatient, emergency department (ED), and inpatient care among 13–30 year-olds from 2006–2015. We stratified outpatient visits, ED visits and inpatient days per person-year (PY) by transmission mode (perinatal (PHIVY), non-perinatal (NPHIVY), age (13–17, 18–23, 24–30 years), CD4 strata (< 200, 200–499, ≥ 500 cells/µL) and presence or absence of viral load (VL) suppression ( Results Among 4,450 AYA (PHIVY: 15%; NPHIVY: 85%), mean (SD) follow-up was 2.8 years (2.5) [PHIVY: 4.2 years (3.1); NPHIVY: 2.5 years (2.3)]. Mean age was 21.4 years (PHIVY: 16.9 years; NPHIVY: 22.3 years) and female sex was 28% (PHIVY: 52%; NPHIVY: 23%). Among PHIVY, most person-time (PT) was spent between ages 13–23 years (13–17 years: 43%; 18–23 years: 45%), CD4 ≥ 500/µL (61%), and VL < 400 c/mL (69%). Among NPHIVY, most PT was spent between ages 24 and 30 years (56%), CD4 ≥ 500/µL (54%), and VL < 400 c/mL (66%). PT spent while prescribed ARVs and VL ≥ 400 c/mL was 30% (PHIVY) and 24% (NPHIVY). For both PHIVY and NPHIVY, outpatient visit rates were higher at younger ages (13–17 years and 18–23 years), lower CD4 (< 200, 200–499/µL), and among those prescribed ARVs (Figure 1). Rates of ED visits and inpatient days were higher during PT spent at older ages (18–23 years, 24–30 years), lower CD4 (< 200, 200–499/µL), and VL ≥ 400 c/mL (Figures 2 and 3). Overall, utilization was higher among PHIVY than NPHIVY (outpatient: 12.1 vs. 6.0/PY; ED: 0.4 vs. 0.3/PY; inpatient: 1.5 vs. 0.8/PY). The overall rate of AIDS-defining conditions was 4.5/100 PY (Figure 4). Conclusion Among AYA with HIV, more ED visits and inpatient days were observed during time spent at older ages, lower CD4 counts, and VL ≥ 400 c/mL. While AIDS-defining conditions were rare, associated resource utilization was substantial. Interventions to improve retention in care, virologic suppression, and immune response may improve outcomes, and thus decrease costly resource utilization, for AYA with HIV as they transition to adulthood. Disclosures All authors: No reported disclosures.

With access to antiretroviral therapy (ART), human immunodeficiency virus (HIV)–infected men and women are living longer and healthier lives and have childbearing desires similar to those of HIV-unaffected individuals [1]. Many are in HIV-serodiscordant sexual partnerships (with an HIV-uninfected partner), and attempts at conception confer sexual HIV transmission risk [2]. HIV risk reduction strategies are available for HIV-serodiscordant couples, in which the male is infected, who want to conceive (Table 1), but there are limited data to inform which or how many concurrent methods a couple should adopt. ART for the HIV-infected male partner is recommended regardless of conception plans, to reduce HIV transmission risk to partners and improve the man’s own health [11, 12]. Because adherence to ART is imperfect and genital shedding of HIV may occur even in the presence of suppressed plasma viral load, couples may seek additional methods to reduce transmission risk. For an uninfected woman wishing to conceive with an infected male partner who is receiving ART, oral preexposure prophylaxis (PrEP) may be a valuable option, particularly if use of ART or ART adherence by the male partner is limited. Combining PrEP for the female partner (oral tenofovir/emtricitabine, or TDF/ FTC) – with ART administration to the male partner for safer conception has been acceptable in observational studies [13–15]. Because PrEP trials were conducted without receipt of ART by the infected partner and ART trials were conducted without receipt of PrEP by the uninfected partner, there are no direct clinical data to estimate the benefit of using PrEP and ART together to decrease periconception HIV transmission risk, compared with either intervention alone. In this issue of The Journal of Infectious Diseases, Hoffman et al use a thoughtfully designed simulation model to investigate the role of PrEP, ART, or both in male-infected, HIV-serodiscordant couples who are attempting to conceive. When clinical data are limited, simulation models can help to inform decision-making. If multiple studies provide partial information, a single model can integrate available data. When data are equivocal or missing, investigators make explicit assumptions about which values to use in a model and then vary these values in sensitivity analyses to identify the thresholds at which decisions would change; this allows readers to understand whether more data are needed to accurately inform clinical choices [16]. Here, Hoffman et al combine transmission risks from separate PrEP trials, ART-as-prevention trials, and observational studies of age-stratified pregnancy rates, and conduct extensive sensitivity analyses on key model parameters. They focus this analysis on couples who maintain the high rates of ART-mediated viral suppression and PrEP adherence seen in the HPTN 052 and Partners PrEP trials [3 ,5, 17, 18]. They also assume that both partners are aware of each others’ HIV status, have been screened and treated for sexually transmitted infections (STIs), and have completed normal fertility evaluations. There are 3 primary messages from their analysis. First, if couples limit condomless sex to the 2 days before and the day of ovulation, and if the male partner is receiving virally suppressive ART, PrEP for the female partner provides little additional benefit. The authors define a “successful” outcome as one in which the female partner remains uninfected and a full-term pregnancy occurs. With ART alone, the yearly chance of this successful outcome is 29.1%; with ART plus PrEP, this chance is 29.2%, which is essentially equivalent within the margin of error of the model results. Second, if couples choose a single intervention, ART for the male partner is projected to be more effective in reducing transmission than PrEP for the female Received and accepted 5 May 2015; electronically published 19 June 2015. Correspondence: Andrea L. Ciaranello, MD, MPH, Division of Infectious Diseases, Massachusetts General Hospital, 50 Staniford St, Rm 936, Boston, MA 02114 (aciaranello@ partners.org). The Journal of Infectious Diseases 2015;212:1525–8 © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of thework, in anymedium, provided theoriginalwork is not altered or transformed in anyway, and that thework is properly cited. For commercial re-use, please contact journals.permissions@oup. com. DOI: 10.1093/infdis/jiv275

As the global community evaluates the unprecedented investment in the scale-up of human immunodeficiency virus (HIV) therapy and considers future investments in HIV care, it is crucial to identify those HIV interventions that maximize the benefit realized from each dollar spent. The use of laboratory monitoring assays--CD4 cell count and HIV RNA level--in decisions about when to initiate and switch antiretroviral therapy may offer substantial clinical benefit, but their economic value remains controversial. Cost-effectiveness analysis can be used to evaluate the value for money of strategies for HIV care, including alternative approaches to laboratory monitoring. Five published cost-effectiveness analyses address the question of CD4 cell count and HIV RNA level monitoring for HIV-infected patients in Africa, with differing conclusions. We describe the use of cost-effectiveness analysis in resource-limited settings and review the cost-effectiveness literature with regard to monitoring the CD4 cell count and HIV RNA level in Africa, highlighting some of the most critical issues in this debate.

Responses to antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected children in resource-limited settings have recently been reported, but outcomes vary. We sought to derive pooled estimates of the 12-month rate of virologic suppression (HIV RNA,400 copies/mL) and gain in CD4 cell percentage (DeltaCD4%) for children initiating ART in resource-limited settings.We conducted a systematic review and meta-analysis of published reports of HIV RNA and CD4 outcomes for treatment-naive children aged 0-17 years old by means of the Medline, EMBASE (Excerpta Medica Database), and LILACS (Latin American and Caribbean Health Sciences Literature) electronic databases and the Cochrane Clinical Trials Register. Pooled estimates of the reported proportion with HIV RNA400 copies/mL and DeltaCD4% after 12 months of ART were derived using patient-level estimates and fixed- and random-effects models. To approximate intention-to-treat analyses, in sensitivity analyses children with missing 12-month data were assumed to have HIV RNA400 copies/mL or DeltaCD4% of zero.In patient-level estimates after 12 months of ART, the pooled proportion with virologic suppression was 70% (95% confidence interval [CI], 67%-73%); the pooled DeltaCD4% was 13.7% (95% CI, 11.8%-15.7%). Results from the fixed- and random-effects models were similar. In approximated intention-to-treat analyses, the pooled estimates decreased to 53% with virologic suppression (95% CI, 50%-55%) and to a DeltaCD4% of 8.5% (95% CI, 5.5%-11.4%).Pooled estimates of reported virologic and immunologic benefits after 12 months of ART among HIV-infected children in resource-limited settings are comparable with those observed among children in developed settings. Consistency in reporting on reasons for missing data will aid in the evaluation of ART outcomes in resource-limited settings.

We used a mathematical model to simulate the conditions necessary for the elimination of mother-to-child transmission of HIV and syphilis in Brazil. Improving access to antenatal care significantly reduces transmission for both diseases, although additional interventions are necessary to meet elimination goals., Background. The Pan-American Health Organization has called for reducing (1) human immunodeficiency virus (HIV) mother-to-child transmission (MTCT) to ≤0.30 infections/1000 live births (LB), (2) HIV MTCT risk to ≤2.0%, and (3) congenital syphilis (CS) incidence to ≤0.50/1000 LB in the Americas by 2015. Methods. Using published Brazilian data in a mathematical model, we simulated a cohort of pregnant women from antenatal care (ANC) through birth. We investigated 2 scenarios: “current access” (89.1% receive one ANC syphilis test and 41.1% receive 2; 81.7% receive one ANC HIV test and 18.9% receive birth testing; if diagnosed, 81.0% are treated for syphilis and 87.5% are treated for HIV) and “ideal access” (95% of women undergo 2 HIV and syphilis screenings; 95% receive appropriate treatment). We conducted univariate and multivariate sensitivity analyses on key inputs. Results. With current access, we projected 2.95 CS cases/1000 LB, 0.29 HIV infections/1000 LB, 7.1% HIV MTCT risk, and 11.11 intrauterine fetal demises (IUFD)/1000 pregnancies, with significant regional variation. With ideal access, we projected improved outcomes: 1.00 CS cases/1000 LB, 0.10 HIV infections/1000 LB, HIV MTCT risk of 2.4%, and 10.65 IUFD/1000 pregnancies. Increased testing drove the greatest improvements. Even with ideal access, only HIV infections/1000 LB met elimination goals. Achieving all targets required testing and treatment >95% and reductions in prevalence and incidence of HIV and syphilis. Conclusions. Increasing access to care and HIV and syphilis antenatal testing will substantially reduce HIV and syphilis MTCT in Brazil. In addition, regionally tailored interventions reducing syphilis incidence and prevalence and supporting HIV treatment adherence are necessary to completely meet elimination goals.