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Understanding the incidence of disease is often crucial for public policy decision-making, as observed during the COVID-19 pandemic. Estimating incidence is challenging, however, when the definition of incidence relies on tests that imperfectly measure disease, as in the case when assays with variable performance are used to detect the SARS-CoV-2 virus. To our knowledge, there are no pragmatic methods to address the bias introduced by the performance of labs in testing for the virus. In the setting of a longitudinal study, we developed a maximum likelihood estimation-based approach to estimate laboratory performance-adjusted incidence using the expectation-maximization algorithm. We constructed confidence intervals (CIs) using both bootstrapped-based and large-sample interval estimator approaches. We evaluated our methods through extensive simulation and applied them to a real-world study (TrackCOVID), where the primary goal was to determine the incidence of and risk factors for SARS-CoV-2 infection in the San Francisco Bay Area from July 2020 to March 2021. Our simulations demonstrated that our method converged rapidly with accurate estimates under a variety of scenarios. Bootstrapped-based CIs were comparable to the large-sample estimator CIs with a reasonable number of incident cases, shown via a simulation scenario based on the real TrackCOVID study. In more extreme simulated scenarios, the coverage of large-sample interval estimation outperformed the bootstrapped-based approach. Results from the application to the TrackCOVID study suggested that assuming perfect laboratory test performance can lead to an inaccurate inference of the incidence. Our flexible, pragmatic method can be extended to a variety of disease and study settings., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: We systematically reviewed the performance of 2010 WHO immunologic and clinical criteria for predicting virologic failure in HIV-infected patients on antiretroviral therapy (ART)., Design: Systematic review., Methods: We used Cochrane Collaboration methods. We calculated unweighted sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of immunologic and clinical criteria for predicting virologic failure., Results: We identified 18 studies. Sixteen assessed immunologic criteria in adults; 12 defined virologic failure as a plasma viral load of more than 50 to more than 1000 copies/ml in adults, three as viral load at least 5000 copies/ml, and two as viral load more than 10,000 copies/ml; the sensitivity ranged from 16.8 to 54.9%, specificity from 82.9 to 95.5%, PPV from 15.0 to 38.8%, and NPV from 90.9 to 98.6%. Seven studies assessed clinical criteria to predict viral load of more than 50 to more than 1000 copies/ml; the sensitivity was 11.0%, specificity 90.5%, PPV 44.9%, and NPV 90.2%. Seven studies assessed clinical or immunologic criteria defining virologic failure as viral load of more than 50 to more than 1000 copies/ml; their sensitivity was 26.6%, specificity 85.9%, PPV 49.4%, and NPV 91.1%. Four studies assessed immunologic criteria in children; three defined virologic failure as viral load at least 5000 copies/ml and one as viral load at least 400 copies/ml. The sensitivity ranged from 4.5 to 6.3%, specificity from 97.7 to 99.3%, PPV from 20.0 to 54.9%, and NPV from 85.5 to 91.8%., Conclusion: The 2010 WHO clinical and immunologic criteria are insensitive and have low PPV for predicting virologic failure. These data support the strong recommendation 2013 treatment guidelines that viral load testing be used to monitor for, diagnose, and confirm ART failure.

Objectives: The objective of this review was to update evidence on when to initiate antiretroviral therapy (ART) to inform revision of the 2013 WHO guidelines for ART in low and middle-income countries., Design: A systematic review and meta-analysis., Methods: We comprehensively searchescohorts. Outcomes were mortality, clinical progression, virologic failure, immunologic recover, and severe adverse events. We pooled data across studies and estimated summary effect sizes. We graded the quality of evidence from the literature for each outcome., Results: We identified 24 studies; 3 were RCTs. Studies found reduced risk of mortality [1 RCT: hazard ratio 0.77, 95% confidence interval (CI) 0.34-1.76; 13 cohorts: relative risk (RR) 0.66, 95% CI 0.55-0.79], progression to AIDS or death (2 RCTs: RR 0.48, 95% CI 0.26-0.91; 9 cohorts: RR 0.70, 95% CI 0.40-1.24) and diagnosis of a non-AIDS-defining illness (1 RCT: RR 0.14, 95% CI 0.03-0.64; 1 cohort: RR 0.47, 95% CI 0.23-0.98), and an increased risk of grade 3/4 laboratory abnormalities in patients initiating ART at at least 350 cells/μl (1 RCT: RR 1.49, 95% CI 1.25-1.77). The quality of evidence was low or very low for clinical outcomes due to few events and imprecision, and high for adverse events., Conclusions: Our findings contributed to the evidence base for the revised 2013 WHO guidelines on ART, which recommend initiating ART at CD4 T-cell counts of 350-500 cells/μl, but not above 500 cells/μl compared to initiating it later when CD4 T-cell counts fall below 350 cells/μl.

Background: Current service delivery systems do not reach all people in need of antiretroviral therapy (ART). In order to inform the operational and service delivery section of the WHO 2013 consolidated antiretroviral guidelines, our objective was to summarize systematic reviews on integrating ART delivery into maternal, newborn, and child health (MNCH) care settings in countries with generalized epidemics, tuberculosis (TB) treatment settings in which the burden of HIV and TB is high, and settings providing opiate substitution therapy (OST); and decentralizing ART into primary health facilities and communities., Design: A summary of systematic reviews., Methods: The reviewers searched PubMed, Embase, PsycINFO, Web of Science, CENTRAL, and the WHO Index Medicus databases. Randomized controlled trials and observational cohort studies were included if they compared ART coverage, retention in HIV care, and/or mortality in MNCH, TB, or OST facilities providing ART with MNCH, TB, or OST facilities providing ART services separately; or primary health facilities or communities providing ART with hospitals providing ART., Results: The reviewers identified 28 studies on integration and decentralization. Antiretroviral therapy integration into MNCH facilities improved ART coverage (relative risk [RR] 1.37, 95% confidence interval [CI] 1.05-1.79) and led to comparable retention in care. ART integration into TB treatment settings improved ART coverage (RR 1.83, 95% CI 1.48-2.23) and led to a nonsignificant reduction in mortality (RR 0.55, 95% CI 0.29-1.05). The limited data on ART integration into OST services indicated comparable rates of ART coverage, retention, and mortality. Partial decentralization into primary health facilities improved retention (RR 1.05, 95% CI 1.01-1.09) and reduced mortality (RR 0.34, 95% CI 0.13-0.87). Full decentralization improved retention (RR 1.12, 95% CI 1.08-1.17) and led to comparable mortality. Community-based ART led to comparable rates of retention and mortality., Conclusion: Integrating ART into MNCH, TB, and OST services was often associated with improvements in ART coverage, and decentralization of ART into primary health facilities and communities was often associated with improved retention. Neither integration nor decentralization was associated with adverse outcomes. These data contributed to recommendations in the WHO 2013 consolidated antiretroviral guidelines to integrate ART delivery into MNCH, TB, and OST services and to decentralize ART.

The objectives of this study were to evaluate whether there were higher rates of primary congenital hypothyroidism (PCH) or elevated concentrations of thyroid-stimulating hormone (TSH) in a community where perchlorate was detected in groundwater wells. The adjusted PCH prevalence ratio and 95% confidence interval (CI) comparing the study community to San Bernardino and Riverside counties combined was 0.45 (95% CI=0.06-1.64). The odds ratios for elevated TSH concentration were 1.24 (95% CI=0.89-1.68) among all newborns screened and 0.69 (95% CI=0.27-1.45) for newborns whose age at screening was 18 hours or greater. Age of the newborn at time of screening was the most important predictor of the TSH level. These findings suggest that residence in a community with potential perchlorate exposure has not impacted PCH rates or newborn thyroid function.

To examine the effect of the revision of the US national AIDS case definition in September 1987, we compared demographic and clinical information for AIDS patients diagnosed and reported to the San Francisco Department of Public Health between 1 September 1987 and 31 October 1989. Of the 3167 patients diagnosed and reported during the study period, 584 (18%) met the revised case definition only, increasing AIDS case reporting in San Francisco by 23%. One hundred and thirty-four of these 584 patients (23%) subsequently developed diagnoses meeting the old definition. After adjusting for this proportion, the revised case definition increased reporting by 17%. The mean time between initial diagnosis with a disease meeting the revised definition and subsequent development of a disease meeting the old definition was 18.5 months. Patients who met the revised case definition only were slightly older and more likely to be Black, female, and intravenous drug users (IVDUs) than those meeting the old case definition. The majority of patients who met the revised case definition only had initial diagnoses of HIV wasting syndrome (26%), HIV encephalopathy (21%), and presumptive Pneumocystis carinii pneumonia (19%). The revised AIDS case definition has significantly increased the reporting of severe morbidity associated with HIV infection, particularly among IVDUs.

To evaluate the epidemiology of HIV infection in Asian and Pacific Islander populations in San Francisco, we compared cases of AIDS reported in Asians and Pacific Islanders with those reported in other racial and ethnic groups. The incidence of AIDS in Asians and Pacific Islanders was significantly lower than in Whites, Blacks, Latinos and American Indians and Alaska natives. AIDS cases among Asians and Pacific Islanders have increased 177% since 1985 compared with 54% in other racial and ethnic groups, with the greatest increase in homosexual and bisexual men and transfusion recipients. Among Asian and Pacific Islander ethnic groups, the incidence of AIDS was 168 cases per 100,000 in Polynesians, 141 per 100,000 in Japanese, 92 per 100,000 in 100 Filipinos, 72 per 100,000 in southeast Asians, and 21 per 100,000 in Chinese. We conclude that AIDS cases are disproportionately increasing in Asians and Pacific Islanders in San Francisco.