Introduction:Laboratory testing is critical for diagnosis and treatment management for people with HIV, but it is costly. When HIV resources are constrained, even before recent disruptions in US funding for the global HIV response, user fees have been used for cost recovery. We describe the availability and charging of user fees for routine HIV laboratory testing globally. Methods:Routine test availability and charging of user fees were examined via an HIV clinic survey conducted September 2020-March 2021; responses reflected clinical practices in 2019. HIV clinics came from 42 low-, middle-, and high-income countries from the International epidemiology Databases to Evaluate AIDS (IeDEA) global research consortium. Results:Across 199 clinics, on-site test availability was generally limited, reflecting constraints in routine test availability across health conditions more broadly. Over 90% of clinics did not report charging user fees. A higher percentage of reporting user fees was from middle-income countries and from countries receiving Global Fund or PEPFAR country support, which may reflect settings with ongoing health funding gaps. Conclusion:Availability and user fees for essential HIV-related laboratory tests were limited in 2019. Monitoring user fees may provide insights about how national health systems are responding to steep reductions in global donor funding.

INTRODUCTION:Since 2013, global HIV treatment guidelines have included recommendations for medication adherence support and monitoring for people on antiretroviral therapy (ART). We examined the implementation of recommended strategies for adherence support and monitoring for adults with HIV through serial cross-sectional structured surveys conducted by the International epidemiology Databases to Evaluate AIDS (IeDEA). METHODS:We used data from surveys completed by HIV clinics across 43 countries in 2017 (n = 206), 2020 (n = 200) and 2023 (n = 214); 131 clinics completed all three surveys. We used descriptive statistics to examine clinic resources and routine adherence support and monitoring at each time point, stratified by country income level (i.e. low/middle-income vs. high-income countries [LMICs/HICs]), and trends among clinics completing all three surveys. We created composite measures of the level or intensity of routine provision of adherence aids/reminders, adherence support and adherence monitoring, ranging from "none" to "enhanced" levels. Among clinics participating in the 2023 survey, we also examined adherence aids and support routinely provided to clients eligible for intensified support versus all clients. RESULTS:At each time point, surveyed clinics were predominantly in LMICs (68.4%-74.3%) and urban settings (65.0%-65.5%), situated within health centres (60.2%-64.0%) or regional/provincial or university hospitals (28.0%-33.5%). Among 131 clinics participating in all surveys, there was a decrease in the provision of multiple adherence readiness counselling sessions from 52.2% of clinics reporting ≥2 sessions before treatment initiation in 2017 to 26.0% in 2023, along with increased provision of 6-month ART refills (from 11.5% to 40.5%). The provision of "enhanced" levels of adherence support to all clients decreased from 2017 to 2023 in both LMICs (64.6% to 28.1%) and HICs (34.3% to 8.6%); in 2023, substantial proportions of clinics reported that such support was routinely provided only to clients eligible for intensive adherence support. At each time point, higher proportions of clinics in LMICs reported "enhanced" adherence monitoring than in HICs (63.5%-70.8% vs. 31.4%-54.3%). CONCLUSIONS:While streamlined provision of ART adherence support may reflect the implementation of guidelines recommending the targeting of support towards clients with known or suspected adherence challenges, further research should examine how evolving clinic adherence support practices are associated with care retention and virologic suppression outcomes.

Introduction:While HIV services have scaled up dramatically under universal treatment recommendations, availability of routine laboratory services for HIV diagnosis and management, and the extent to which user fees are charged for these services, are not well documented. We described site-level availability and user fees for adult HIV laboratory testing among 238 sites in 42 countries of the International epidemiology Databases to Evaluate AIDS (IeDEA) global consortium, and contextualized practices by site- and country-level characteristics, including country income level and receipt of Global Fund or PEPFAR support. Methods:Availability of HIV-related laboratory services and charging of user fees, were examined via an IeDEA site assessment survey conducted September 2020-March 2021, with responses reflecting practices in 2019. Laboratory services examined included: HIV-1/HIV-2 antigen/antibody immunoassay test (HIV-1/2 Ag/Ab), HIV-1 p24 antigen test (p24), supplemental HIV-1/HIV-2 antibody differentiation immunoassay (HIV-1/2 Ab suppl), quantitative PCR for HIV viral load (VL), HIV-1 genotypic drug resistance testing (genotyping), and CD4 count testing (CD4). Availability was defined as provided on-site in the HIV clinic or within the same health facility. User fees were fees other than insurance co-pays paid for a given test, conditional on their on-site availability. We reported frequencies and percentages of site-level availability and user fees, overall and by site- and country-level characteristics. Results:Most sites (88%) reported HIV-1/HIV-2 Ag/Ab availability on-site, while fewer than half of sites reported having p24 and HIV-1/2 Ab suppl available. Approximately half of sites reported VL and CD4 testing availability, while less than one-third of sites (28%) reported genotyping availability. The percentage of sites reporting user fees ranged from 6.5% (HIV-1/2 Ag/Ab) to 10.5% (CD4). A higher percentage of sites reporting user fees were from upper-middle income countries, countries receiving any Global Fund or any PEPFAR country support, and the Asia-Pacific region. Conclusions:While most HIV care sites participating in IeDEA did not charge user fees for HIV-related laboratory tests in 2019, on-site availability of such tests was limited. Continued action to identify and address constraints in the routine provision of these laboratory services is critical for appropriate management of HIV.

Introduction Tuberculosis (TB) is a leading infectious cause of death globally. It is the most common opportunistic infection in people living with HIV, and the most common cause of their morbidity and mortality. Following TB treatment, surviving individuals may be at risk for post-TB lung disease. The TB Sentinel Research Network (TB-SRN) provides a platform for coordinated observational TB research within the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium.Methods and analysis This prospective, observational cohort study will assess treatment and post-treatment outcomes of pulmonary TB (microbiologically confirmed or clinically diagnosed) among 2600 people aged ≥15 years, with and without HIV coinfection, consecutively enrolled at 16 sites in 11 countries, across 6 of IeDEA’s global regions. Data regarding clinical and sociodemographic factors, mental health, health-related quality of life, pulmonary function, and laboratory and radiographic findings will be collected using standardised questionnaires and data collection tools, beginning from the initiation of TB treatment and through 12 months after the end of treatment. Data will be aggregated for proposed analyses.Ethics and dissemination Ethics approval was obtained at all implementing study sites, including the Vanderbilt University Medical Center Human Research Protections Programme. Participants will provide informed consent; for minors, this includes both adolescent assent and the consent of their parent or primary caregiver. Protections for vulnerable groups are included, in alignment with local standards and considerations at sites. Procedures for requesting use and analysis of TB-SRN data are publicly available. Findings from TB-SRN analyses will be shared with national TB programmes to inform TB programming and policy, and disseminated at regional and global conferences and other venues.

Introduction:Socioeconomic status (SES) influences well-being among people living with HIV (people with HIV [PWH]); when individual-level SES information is not available, area-level SES indicators may be a suitable alternative. We hypothesized that (1) select ZIP code-level SES indicators would be associated with viral suppression and (2) accounting for ZIP code-level SES would attenuate racial disparities in viral suppression among PWH.Setting:The NA-ACCORD, a collaboration of clinical and interval cohorts of PWH, was used.Methods:Participants with >= 1 viral load measurement and >= 1 US residential 5-digit ZIP code(s) between 2010 and 2018 were included. In this serial cross-sectional analysis, multivariable logistic regression models were used to quantify the annual association of race and ethnicity with viral suppression, in the presence of SES indicators and sex, hepatitis C status, and age.Results:We observed a dose-response relationship between SES factors and viral suppression. Lower income and education were associated with 0.5-0.7-fold annual decreases in odds of viral suppression. We observed racial disparities of approximately 40% decreased odds of viral suppression among non-Hispanic Black compared with non-Hispanic White participants. The disparity persisted but narrowed by 3%-4% when including SES in the models.Conclusions:ZIP code-based SES was associated with viral suppression, and accounting for SES narrowed racial disparities in viral suppression among PWH in the NA-ACCORD. Inclusion of ZIP code-level indicators of SES as surrogates for individual-level SES should be considered to improve our understanding of the impact of social determinants of health and racial disparities on key outcomes among PWH in North America.

Background: Overwhelming evidence highlights the negative impact of substance use on HIV care and treatment outcomes. Yet, the extent to which alcohol use disorder (AUD) and other substance use disorders (SUD) services have been integrated within HIV clinical settings is limited. We describe AUD/SUD screening and treatment availability in HIV clinical sites participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. Methods: In 2020, 223 IeDEA HIV clinical sites from 41 countries across seven geographic regions completed a survey on capacity and practices related to management of AUD/ SUD. Sites provided information on AUD and other SUD screening and treatment practices. Results: Sites were from low-income countries (23%), lower-middle-income countries (38%), upper-middle income countries (17%) and high-income counties (23%). AUD and SUD screening using validated instruments were reported at 32% (n=71 located in 12 countries) and 12% (n=27 located in 6 countries) of the 223 sites from 41 countries, respectively. The North American region had the highest proportion of clinics that reported AUD screening (76%), followed by East Africa (46%); none of the sites in West or Central Africa reported AUD screening. 31% (n=69) reported both AUD screening and counseling, brief intervention, psychotherapy, or Screening, Brief Intervention, and Referral to Treatment; 8% (n=18) reported AUD screening and detox hospitalization; and 10% (n=24) reported both AUD screening and medication. While the proportion of clinics providing treatment for SUD was lower than those treating AUD, the prevalence estimates of treatment availability were similar. Conclusions: Availability of screening and treatment for AUD/SUD in HIV care settings is limited, leaving a substantial gap for integration into ongoing HIV care. A critical understanding is needed of the multilevel implementation factors or feasible implementation strategies for integrating screening and treatment of AUD/ SUD into HIV care settings, particularly for resource -constrained regions.

Introduction Timely descriptions of HIV service characteristics and their evolution over time across diverse settings are important for monitoring the scale-up of evidence-based program strategies, understanding the implementation landscape, and examining service delivery factors that influence HIV care outcomes. Methods The International epidemiology Databases to Evaluate AIDS (IeDEA) consortium undertakes periodic cross-sectional surveys on service availability and care at participating HIV treatment sites to characterize trends and inform the scientific agenda for HIV care and implementation science communities. IeDEA’s 2020 general site assessment survey was developed through a consultative, 18-month process that engaged diverse researchers in identifying content from previous surveys that should be retained for longitudinal analyses and in developing expanded and new content to address gaps in the literature. An iterative review process was undertaken to standardize the format of new survey questions and align them with best practices in survey design and measurement and lessons learned through prior IeDEA site assessment surveys. Results The survey questionnaire developed through this process included eight content domains covered in prior surveys (patient population, staffing and community linkages, HIV testing and diagnosis, new patient care, treatment monitoring and retention, routine HIV care and screening, pharmacy, record-keeping and patient tracing), along with expanded content related to antiretroviral therapy (differentiated service delivery and roll-out of dolutegravir-based regimens); mental health and substance use disorders; care for pregnant/postpartum women and HIV-exposed infants; tuberculosis preventive therapy; and pediatric/adolescent tuberculosis care; and new content related to Kaposi’s sarcoma diagnostics, the impact of COVID-19 on service delivery, and structural barriers to HIV care. The survey was distributed to 238 HIV treatment sites in late 2020, with a 95% response rate. Conclusion IeDEA’s approach for site survey development has broad relevance for HIV research networks and other priority health conditions.

Background: While recognized as a key HIV prevention strategy, preexposure prophylaxis (PrEP) availability and accessibility are not well documented globally. We aimed to describe PrEP drug registration status and the availability of PrEP services across HIV care sites participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium. Methods: We used country-level PrEP drug registration status from the AIDS Vaccine Advocacy Coalition and data from IeDEA surveys conducted in 2014, 2017 and 2020 among participating HIV clinics in seven global regions. We used descriptive statistics to assess PrEP availability across IeDEA sites serving adult patients in 2020 and examined trends in PrEP availability among sites that responded to all three surveys. Results: Of 199 sites that completed the 2020 survey, PrEP was available in 161 (81%). PrEP availability was highest at sites in North America (29/30; 97%) and East Africa (70/74; 95%) and lowest at sites in Central (10/20; 50%) and West Africa (1/6; 17%). PrEP availability was higher among sites in countries where PrEP was officially registered (146/161; 91%) than where it was not (14/32; 44%). Availability was higher at health centers (109/120; 90%) and district hospitals (14/16; 88%) compared to regional/teaching hospitals (36/63). Among the 94 sites that responded to all three surveys, PrEP availability increased from 47% in 2014 to 60% in 2017 and 76% in 2020. Conclusion: PrEP availability has substantially increased since 2014 and is now available at most IeDEA sites. However, PrEP service provision varies markedly across global regions.

Abstract Introduction Interruptions in treatment pose risks for people with HIV (PWH) and threaten progress in ending the HIV epidemic; however, the COVID‐19 pandemic's impact on HIV service delivery across diverse settings is not broadly documented. Methods From September 2020 to March 2021, the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium surveyed 238 HIV care sites across seven geographic regions to document constraints in HIV service delivery during the first year of the pandemic and strategies for ensuring care continuity for PWH. Descriptive statistics were stratified by national HIV prevalence (<1%, 1–4.9% and ≥5%) and country income levels. Results Questions about pandemic‐related consequences for HIV care were completed by 225 (95%) sites in 42 countries with low (n = 82), medium (n = 86) and high (n = 57) HIV prevalence, including low‐ (n = 57), lower‐middle (n = 79), upper‐middle (n = 39) and high‐ (n = 50) income countries. Most sites reported being subject to pandemic‐related restrictions on travel, service provision or other operations (75%), and experiencing negative impacts (76%) on clinic operations, including decreased hours/days, reduced provider availability, clinic reconfiguration for COVID‐19 services, record‐keeping interruptions and suspension of partner support. Almost all sites in low‐prevalence and high‐income countries reported increased use of telemedicine (85% and 100%, respectively), compared with less than half of sites in high‐prevalence and lower‐income settings. Few sites in high‐prevalence settings (2%) reported suspending antiretroviral therapy (ART) clinic services, and many reported adopting mitigation strategies to support adherence, including multi‐month dispensing of ART (95%) and designating community ART pick‐up points (44%). While few sites (5%) reported stockouts of first‐line ART regimens, 10–11% reported stockouts of second‐ and third‐line regimens, respectively, primarily in high‐prevalence and lower‐income settings. Interruptions in HIV viral load (VL) testing included suspension of testing (22%), longer turnaround times (41%) and supply/reagent stockouts (22%), but did not differ across settings. Conclusions While many sites in high HIV prevalence settings and lower‐income countries reported introducing or expanding measures to support treatment adherence and continuity of care, the COVID‐19 pandemic resulted in disruptions to VL testing and ART supply chains that may negatively affect the quality of HIV care in these settings.

PURPOSE:Use of electronic health records (EHRs) in health research may lead to the false assumption of complete event ascertainment. We estimated "observation windows" (OWs), defined as periods within which the assumption of complete ascertainment of events is more likely to hold, as a quality control approach to reducing the likelihood of this false assumption. We demonstrated the impact of OWs on estimating the rates of type II diabetes mellitus (diabetes) from HIV clinical cohorts. METHODS:Data contributed by 16 HIV clinical cohorts to the NA-ACCORD were used to identify and evaluate OWs for an operationalized definition of diabetes occurrence as a case study. Procedures included (1) gathering cohort-level data; (2) visualizing and summarizing gaps in observations; (3) systematically establishing start and stop dates during which the assumption of complete ascertainment of diabetes events was reasonable; and (4) visualizing the diabetes OWs relative to the cohort open and close dates to identify immortal person-time. We estimated diabetes occurrence event rates and 95% confidence intervals in the most recent decade that data were available (January 1, 2007, to December 31, 2016). RESULTS:The number of diabetes events decreased by 17% with the use of the diabetes OWs; immortal person-time was removed decreasing total person-years by 23%. Consequently, the diabetes rate increased from 1.23 (95% confidence interval [1.20, 1.25]) per 100 person-years to 1.32 [1.29, 1.35] per 100 person-years with the use of diabetes OWs. CONCLUSIONS:As the use of EHR-curated data for event-driven health research continues to expand, OWs have utility as a quality control approach to complete event ascertainment, helping to improve accuracy of estimates by removing immortal person-time when ascertainment is incomplete.

INTRODUCTION:Since 2015, the World Health Organization (WHO) has recommended that all people living with HIV (PLHIV) initiate antiretroviral treatment (ART), irrespective of CD4+ count or clinical stage. National adoption of universal treatment has accelerated since WHO's 2015 "Treat All" recommendation; however, little is known about the translation of this guidance into practice. This study aimed to assess the status of Treat All implementation across regions, countries, and levels of the health care delivery system. METHODS:Between June and December 2017, 201/221 (91%) adult HIV treatment sites that participate in the global IeDEA research consortium completed a survey on capacity and practices related to HIV care. Located in 41 countries across seven geographic regions, sites provided information on the status and timing of site-level introduction of Treat All, as well as site-level practices related to ART initiation. RESULTS:Almost all sites (93%) reported that they had begun implementing Treat All, and there were no statistically significant differences in site-level Treat All introduction by health facility type, urban/rural location, sector (public/private) or country income level. The median time between national policy adoption and site-level introduction was one month. In countries where Treat All was not yet adopted in national guidelines, 69% of sites reported initiating all patients on ART, regardless of clinical criteria, and these sites had been implementing Treat All for a median period of seven months at the time of the survey. The majority of sites (77%) reported typically initiating patients on ART within 14 days of confirming diagnosis, with 60% to 62% of sites implementing Treat All in East, Southern and West Africa reporting same-day ART initiation for most patients. CONCLUSIONS:By mid- to late-2017, the Treat All strategy was the standard of care at almost all IeDEA sites, including rural, primary-level health facilities in low-resource settings. While further assessments of site-level capacity to provide high-quality HIV care under Treat All and to support sustained viral suppression after ART initiation are needed, the widespread introduction of Treat All at the service delivery level is a critical step towards global targets for ending the HIV epidemic as a public health threat.

We modeled global time trends in median CD4 cell counts at combination antiretroviral therapy initiation in human immunodeficiency virus-infected adults. These counts have increased in all country income groups since 2002 but generally remained below 350/mu L in 2015.Early initiation of combination antiretroviral therapy (cART), at higher CD4 cell counts, prevents disease progression and reduces sexual transmission of human immunodeficiency virus (HIV). We describe the temporal trends in CD4 cell counts at the start of cART in adults from low-income, lower-middle-income, upper-middle-income, and high-income countries (LICs, LMICs, UMICs, and HICs, respectively). We included HIV-infected individuals aged a parts per thousand16 years who started cART between 2002 and 2015 in a clinic participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) or the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). Missing CD4 cell counts at the start of cART were estimated through multiple imputation. Weighted mixed-effect models were used to smooth trends in median CD4 cell counts. A total of 951855 adults from 16 LICs, 11 LMICs, 9 UMICs, and 19 HICs were included. Overall, the modeled median CD4 cell count at the start of cART increased from 2002 to 2015, from 78/A mu L (95% confidence interval, 58-104/A mu L) to 287/A mu L (250-328/A mu L) in LICs, from 99/A mu L (71-140/A mu L) to 234/A mu L (192-285/A mu L) in LMICs, from 71/A mu L (49-104/A mu L) to 311/A mu L (255-379/A mu L) in UMICs, and from 161/A mu L (143-181/A mu L) to 327/A mu L (286-372/A mu L) in HICs. In LICs, LMICs, and UMICs, the increase was more pronounced in women; in HICs, the opposite was observed. Median CD4 cell counts at the start of cART increased in all income groups, but generally remained below 350/mu L in 2015. Substantial additional efforts and resources are required to achieve earlier diagnosis, linkage to care, and initiation of cART.

Introduction: An important determinant of the effectiveness of HIV treatment programs is the capacity of sites to implement recommended services and identify systematic changes needed to ensure that invested resources translate into improved patient outcomes. We conducted a survey in 2014 of HIV care and treatment sites in the seven regions of the International epidemiologic Database to Evaluate AIDS (IeDEA) Consortium to evaluate facility characteristics, HIV prevention, care and treatment services provided, laboratory capacity, and trends in the comprehensiveness of care compared to data obtained in the 2009 baseline survey.Methods: Clinical staff from 262 treatment sites in 45 countries in IeDEA completed a site survey from September 2014 to January 2015, including Asia-Pacific with Australia (n = 50), Latin America and the Caribbean (n = 11), North America (n = 45), Central Africa (n = 17), East Africa (n = 36), Southern Africa (n = 87), and West Africa (n = 16). For the 55 sites with complete data from both the 2009 and 2014 survey, we evaluated change in comprehensiveness of care.Results: The majority of the 262 sites (61%) offered seven essential services (ART adherence, nutritional support, PMTCT, CD4+ cell count testing, tuberculosis screening, HIV prevention, and outreach). Sites that were publicly funded (64%), cared for adults and children (68%), low or middle Human Development Index (HDI) rank (68%, 68%), and received PEPFAR support (71%) were most often fully comprehensive. CD4+ cell count testing was universally available (98%) but only 62% of clinics offered it onsite. Approximately two-thirds (69%) of sites reported routine viral load testing (44-100%), with 39% having it onsite. Laboratory capacity to monitor antiretroviral-related toxicity and diagnose opportunistic infections varied widely by testing modality and region. In the subgroup of 55 sites with two surveys, comprehensiveness of services provided significantly increased across all regions from 2009 to 2014 (5.7 to 6.5, p < 0.001).Conclusions: The availability of viral load monitoring remains suboptimal and should be a focus for site capacity, particularly in East and Southern Africa, where the majority of those initiating on ART reside. However, the comprehensiveness of care provided increased over the past 5 years and was related to type of funding received (publicly funded and PEPFAR supported).

Background: Tuberculosis (TB) risk and mortality increase in the 6 months after highly active antiretroviral therapy (HAART) initiation. This short-term risk may be a consequence of HAART initiation and immune reconstitution. Alternatively, it may be due to confounding by low CD4+ counts and high HIV viral loads (VLs). We assessed the TB risk before and after HAART initiation while appropriately controlling for time-updated laboratory values and HAART exposure. Methods: We conducted an observational cohort study among persons enrolled in the North American AIDS Cohort Collaboration on Research and Design from 1998 through 2011. A marginal structural model was constructed to estimate the association of HAART initiation and TB risk. Inverse probability weights for the probability of HAART initiation were incorporated. Results: Among 26,342 patients, 94 cases of TB were diagnosed during 147,557 person-years (p-y) of follow-up. The unadjusted TB rates were 93/100,000 p-y [95% confidence interval (CI): 63 to 132] before HAART initiation, 203/100,000 p-y (95% CI: 126 to 311) ≤6 months after HAART initiation, and 40/100,000 p-y (95% CI: 29 to 55) >6 months on HAART. After controlling for time-updated laboratory values, the adjusted odds of TB ≤6 months after HAART initiation and >6 months was 0.65 (95% CI: 0.28 to 1.51) and 0.29 (95% CI: 0.16 to 0.53), respectively. Conclusions: TB risk in the first 6 months after HAART initiation is not higher than that before HAART initiation after adjusting for CD4+ count and VLs. These findings suggest that short-term TB risk may be related to low CD4+ counts and high VLs near HAART initiation and support early HAART initiation to decrease TB risk.

Targeted spontaneous reporting (TSR) is a pharmacovigilance method that can enhance reporting of adverse drug reactions related to antiretroviral therapy (ART). Minimal data exist on the needs or capacity of facilities to conduct TSR.

The burden of HIV disease has shifted from traditional AIDS-defining illnesses to serious non-AIDS-defining comorbid conditions. Research aimed at improving HIV-related comorbid disease outcomes requires well-defined, verified clinical endpoints. We developed methods to ascertain and verify end-stage renal disease (ESRD) and end-stage liver disease (ESLD) and validated screening algorithms within the largest HIV cohort collaboration in North America (NA-ACCORD). Individuals who screened positive among all participants in twelve cohorts enrolled between January 1996 and December 2009 underwent medical record review to verify incident ESRD or ESLD using standardized protocols. We randomly sampled 6% of contributing cohorts to determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ESLD and ESRD screening algorithms in a validation subcohort. Among 43,433 patients screened for ESRD, 822 screened positive of which 620 met clinical criteria for ESRD. The algorithm had 100% sensitivity, 99% specificity, 82% PPV, and 100% NPV for ESRD. Among 41,463 patients screened for ESLD, 2,024 screened positive of which 645 met diagnostic criteria for ESLD. The algorithm had 100% sensitivity, 95% specificity, 27% PPV, and 100% NPV for ESLD. Our methods proved robust for ascertainment of ESRD and ESLD in persons infected with HIV.

BACKGROUND Screening for tuberculosis prior to highly active antiretroviral therapy (HAART) initiation is not routinely performed in low-incidence settings. Identifying factors associated with developing tuberculosis after HAART initiation could focus screening efforts. METHODS Sixteen cohorts in the United States and Canada contributed data on persons infected with human immunodeficiency virus (HIV) who initiated HAART December 1995-August 2009. Parametric survival models identified factors associated with tuberculosis occurrence. RESULTS Of 37845 persons in the study, 145 were diagnosed with tuberculosis after HAART initiation. Tuberculosis risk was highest in the first 3 months of HAART (20 cases; 215 cases per 100000 person-years; 95% confidence interval [CI]: 131-333 per 100000 person-years). In a multivariate Weibull proportional hazards model, baseline CD4+ lymphocyte count <200, black race, other nonwhite race, Hispanic ethnicity, and history of injection drug use were independently associated with tuberculosis risk. In addition, in a piece-wise Weibull model, increased baseline HIV-1 RNA was associated with increased tuberculosis risk in the first 3 months; male sex tended to be associated with increased risk. CONCLUSIONS Screening for active tuberculosis prior to HAART initiation should be targeted to persons with baseline CD4 <200 lymphocytes/mm³ or increased HIV-1 RNA, persons of nonwhite race or Hispanic ethnicity, history of injection drug use, and possibly male sex.

BACKGROUNDThe optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain.METHODSWe conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group).RESULTSIn the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P<0.001). In the second analysis involving 9155 patients, 2220 (24%) initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter and 6935 (76%) deferred therapy. Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% (relative risk, 1.94; 95% CI, 1.37 to 2.79; P<0.001).CONCLUSIONSThe early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy.

Stephen J Gange, Mari M Kitahata, Michael S Saag, David R Bangsberg, Ronald J Bosch, John T Brooks, Liviana Calzavara, Steven G Deeks, Joseph J Eron, Kelly A Gebo, M John Gill, David W Haas, Robert S Hogg, Michael A Horberg, Lisa P Jacobson, Amy C Justice, Gregory D Kirk, Marina B Klein, Jeffrey N Martin, Rosemary G McKaig, Benigno Rodriguez, Sean B Rourke, Timothy R Sterling, Aimee M Freeman and Richard D Moorey*