Real-world evaluation of linezolid-associated serotonin toxicity with and without concurrent serotonergic agents.

BACKGROUND: The risk of linezolid-associated serotonin toxicity remains unclear. This study sought to evaluate the incidence of serotonin toxicity among hospitalized patients who received linezolid with or without concurrent serotonergic agents (SAs). Secondary outcomes were to assess the dose, agent selection and number of SAs. METHODS: A single-centre, retrospective cohort study of hospitalized patients aged ≥18 years who received at least one dose of linezolid with or without SAs between 1 January 2014 and 30 June 2021 was performed. Patients were excluded if they were aged <18 years, had linezolid ordered but not administered, were pregnant or were incarcerated. Up to five concurrent SAs were assessed, and dose category was classed as low, moderate or high (dose <33%, 33-66% or >66% of maximum daily dose, respectively). Serotonin toxicity was identified by searching patients' electronic medical records. If identified, the Sternbach criteria and Hunter criteria were applied. RESULTS: Of 2022 patients screened, 1743 were included in this study. Mean age, weight and linezolid duration were 58.5 years, 90.7 kg and 3.8 days, respectively. Approximately 67% (1168/1743) of patients received linezolid with at least one SA, and several patients received multiple SAs. Most patients (53.8%; 616/1144) received moderate- and/or high-dose SAs. Only two patients (0.11%) were identified as possible cases of serotonin toxicity based on the electronic medical record search. However, the incidence of serotonin toxicity was 0.06% (1/1743) based on the Sternbach criteria and 0% (0/1743) based on the Hunter criteria. CONCLUSIONS: Serotonin toxicity among hospitalized patients who received linezolid with or without SAs was exceedingly rare, even among those who received multiple and high-dose SAs.

Perceived access to PrEP as a critical step in engagement: A qualitative analysis and discrete choice experiment among young men who have sex with men.

Young Men who have Sex with Men (MSM) continue to face disproportionate HIV risk. Despite its well accepted role in HIV prevention, pre-exposure prophylaxis (PrEP) uptake remains below desired goals. Systemic barriers to PrEP access, including insurance complexity, cost, and wait times to start PrEP may contribute to low PrEP engagement. We conducted in-depth interviews and designed a discrete choice experiment (DCE) to assess preferences for and barriers to PrEP access in the United States. METHODS: We conducted in-depth interviews with 18 MSM aged 18-30 years old who were not on PrEP and created a DCE based on the results. For the DCE, a convenience sample of young MSM in the United States who reported recent condomless anal sex was recruited through social media applications. Consenting participants provided sociodemographic information and responded to a series of 10 choice tasks about PrEP access. Preferences were analyzed utilizing marginal willingness-to-pay (mWTP) methods. RESULTS: In-depth interviews revealed preferences for highly effective PrEP and concerns about barriers to access due to insurance coverage and privacy. The online DCE was completed by 236 eligible MSM aged 18-30. The most-preferred PrEP package-with all elements significantly preferred over other options-was insurance covered, could be maintained confidential from parents and employers, was available immediately, and had an online option. Need to take out new insurance or add a supplemental insurance in order to cover PrEP significantly detracted from willingness to pay for a PrEP program. Attributes most associated with willingness to pay for PrEP were PrEP being covered by an insurance the client already has and insurance coverage that was private. CONCLUSIONS: Young MSM at high risk for HIV in the United States who are not currently on PrEP showed strong preferences for PrEP options that were covered by insurance and could be kept confidential from parents and employers. Lack of these options may present major barriers to PrEP access among young MSM who are at particularly high risk. Rapid access to PrEP, as well as the option of receiving some care online, may also enhance PrEP uptake.

Successful treatment with secnidazole for trichomoniasis in the setting of metronidazole hypersensitivity.

Limited effective treatment options currently exist for trichomoniasis management among patients with metronidazole hypersensitivity. We report a patient with a documented history of metronidazole hypersensitivity who initially was treated with nitazoxanide but demonstrated clinical and microbiological failure. Secnidazole was subsequently used for treatment, which resulted in clinical and microbiological cure without observation of cross-reactivity. Secnidazole may represent a potential treatment option for trichomoniasis in patients with metronidazole hypersensitivity after consultation with an infectious disease specialist.

Predictors of mortality in treatment experienced HIV-infected patients in northern Tanzania.

BACKGROUND: While factors that drive early mortality among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in sub-Saharan Africa (SSA) have been described, less is known about the predictors of long-term mortality for those with ART experience. METHODS: PLWH and on ART attending two HIV treatment clinics in Moshi, Tanzania were enrolled from 2008 through 2009 and followed for 3.5 years. Demographic, psychosocial, and clinical information were collected at enrollment. Plasma HIV RNA measurements were collected annually. Cause of death was adjudicated by two independent reviewers based on verbal autopsy information and medical records. Bivariable and multivariable analyses were conducted using Cox proportional hazard models to identify predictors of mortality. RESULTS: The analysis included 403 participants. The median (IQR) age in years was 42 (36-48) and 277 (68.7%) participants were female. The proportion of participants virologically suppressed during the 4 collection time points was 88.5%, 94.7%, 91.5%, and 94.5%. During follow-up, 24 participants died; the overall mortality rate was 1.8 deaths per 100 person-years. Of the deaths, 14 (58.3%) were suspected to be HIV/AIDS related. Predictors of mortality (adjusted hazard ratio, 95% confidence interval) were male sex (2.63, 1.01-6.83), secondary or higher education (7.70, 3.02-19.60), receiving care at the regional referral hospital in comparison to the larger zonal referral hospital (6.33, 1.93-20.76), and moderate to severe depression symptoms (6.35, 1.69-23.87). CONCLUSIONS: As ART coverage continues to expand in SSA, HIV programs should recognize the need for interventions to promote HIV care engagement for men and the integration of mental health screening and treatment with HIV care. Facility-level barriers may contribute to challenges faced by PLWH as they progress through the HIV care continuum, and further understanding of these barriers is needed. The association of higher educational attainment with mortality merits further investigation.

Test site predicts HIV care linkage and antiretroviral therapy initiation: a prospective 3.5 year cohort study of HIV-positive testers in northern Tanzania.

BACKGROUND: Linkage to HIV care is crucial to the success of antiretroviral therapy (ART) programs worldwide, loss to follow up at all stages of the care continuum is frequent, and long-term prospective studies of care linkage are currently lacking. METHODS: Consecutive clients who tested HIV-positive were enrolled from four HIV testing centers (1 health facility and 3 community-based centers) in the Kilimanjaro region of Tanzania as part of the larger Coping with HIV/AIDS in Tanzania (CHAT) prospective observational study. Biannual interviews were conducted over 3.5 years, assessing care linkage, retention, and mental health. Bivariable and multivariate logistic regression analyses were conducted to determine associations with early death (prior to the second follow up interview) and delayed (>6 months post-test) or failed care linkage. RESULTS: A total of 263 participants were enrolled between November, 2008 and August, 2009 and 240 participants not already linked to care were retained in the final dataset. By 6 months after enrollment, 169 (70.4 %) of 240 participants had presented to an HIV care and treatment facility; 41 (17.1 %) delayed more than 6 months, 15 (6.3 %) died, and 15 (6.3 %) were lost to follow up. Twenty-six patients died before their second follow up visit and were analyzed in the early death group (10.8 %). Just 15 (9.6 %) of those linked to care had started ART within 6 months, but 123 (89.1 %) of patients documented to be ART eligible by local guidelines had started ART by the end of 3.5 years. On multivariate analysis, male gender (OR 1.72; 95 % CI 1.08, 2.75), testing due to illness (OR 1.63; 95 % CI 1.01, 2.63), and higher mean depression scale scores (4 % increased risk per increase in depression score; 95 % CI 1 %, 8 %) were associated with early death. Testing at a community versus a hospital-based site (OR 2.89; 95 % CI 1.79, 4.66) was strongly associated with delaying or never entering care. CONCLUSIONS: Nearly 30 % of the cohort did not have timely care linkage, ART initiation was frequently delayed, and testing at a hospital outpatient department versus community-based testing centers was strongly associated with successful care linkage.

Challenges of Maintaining Good Clinical Laboratory Practices in Low-Resource Settings: A Health Program Evaluation Framework Case Study From East Africa.

OBJECTIVES: Using a clinical research laboratory as a case study, we sought to characterize barriers to maintaining Good Clinical Laboratory Practice (GCLP) services in a developing world setting. METHODS: Using a US Centers for Disease Control and Prevention framework for program evaluation in public health, we performed an evaluation of the Kilimanjaro Christian Medical Centre-Duke University Health Collaboration clinical research laboratory sections of the Kilimanjaro Clinical Research Institute in Moshi, Tanzania. Laboratory records from November 2012 through October 2014 were reviewed for this analysis. RESULTS: During the 2-year period of study, seven instrument malfunctions suspended testing required for open clinical trials. A median (range) of 9 (1-55) days elapsed between instrument malfunction and biomedical engineer service. Sixteen (76.1%) of 21 suppliers of reagents, controls, and consumables were based outside Tanzania. Test throughput among laboratory sections used a median (range) of 0.6% (0.2%-2.7%) of instrument capacity. Five (55.6%) of nine laboratory technologists left their posts over 2 years. CONCLUSIONS: These findings demonstrate that GCLP laboratory service provision in this setting is hampered by delays in biomedical engineer support, delays and extra costs in commodity procurement, low testing throughput, and high personnel turnover.

Durability of antiretroviral therapy and predictors of virologic failure among perinatally HIV-infected children in Tanzania: a four-year follow-up.

BACKGROUND: In Tanzania, HIV-1 RNA testing is rarely available and not standard of care. Determining virologic failure is challenging and resistance mutations accumulate, thereby compromising second-line therapy. We evaluated durability of antiretroviral therapy (ART) and predictors of virologic failure among a pediatric cohort at four-year follow-up. METHODS: This was a prospective cross-sectional study with retrospective chart review evaluating a perinatally HIV-infected Tanzanian cohort enrolled in 2008-09 with repeat HIV-1 RNA in 2012-13. Demographic, clinical, and laboratory data were extracted from charts, resistance mutations from 2008-9 were analyzed, and prospective HIV RNA was obtained. RESULTS: 161 (78%) participants of the original cohort consented to repeat HIV RNA. The average age was 12.2 years (55% adolescents ≥12 years). Average time on ART was 6.4 years with 41% receiving second-line (protease inhibitor based) therapy. Among those originally suppressed on a first-line (non-nucleoside reverse transcriptase based regimen) 76% remained suppressed. Of those originally failing first-line, 88% were switched to second-line and 72% have suppressed virus. Increased level of viremia and duration of ART trended with an increased number of thymidine analogue mutations (TAMs). Increased TAMs increased the odds of virologic failure (p = 0.18), as did adolescent age (p < 0.01). CONCLUSIONS: After viral load testing in 2008-09 many participants switched to second-line therapy. The majority achieved virologic suppression despite multiple resistance mutations. Though virologic testing would likely hasten the switch to second-line among those failing, methods to improve adherence is critical to maximize durability of ART and improve virologic outcomes among youth in resource-limited settings.

Effect of free distribution of safety equipment on usage among motorcycle-taxi drivers in Tanzania--A cluster randomised controlled trial.

INTRODUCTION: Deaths due to road traffic injuries, particularly motorcycle crashes, have increased rapidly in many African nations and context-specific strategies to improve preventative behaviours are needed. Although adhering to conspicuity measures by wearing reflective safety vests is a highly effective crash prevention strategy and mandated by law among motorcycle-taxi drivers in some African countries, actual use is currently low. We aimed to test whether eliminating cost-barriers through the provision of free reflective, fluorescent motorcycle safety vests would lead to increased utilisation among a high-risk population of motorcycle-taxi drivers in Tanzania. METHODS: A cluster randomised controlled trial was conducted among 180 motorcycle-taxi drivers. Participants randomised to the intervention arm (90) received free, reflective, fluorescent vests; participants randomised to the control arm (90) did not receive free vests. Participants' use of reflective vests was then observed on city streets over a three month period and differential uptake was estimated using mixed-effects logistic regression. RESULTS: Baseline use of reflective vests was 3.3% in both arms. Seventy-nine drivers in the intervention arm and 82 drivers in the control arm were observed during follow-up. The average proportion of observations during which motorcycle drivers were using a reflective vest was 9.5% in the intervention arm, compared to 2.0% in the control arm (odds ratio: 5.5, 95% confidence interval: 1.1-26.9, p-value: 0.04). CONCLUSION: Although distribution of free reflective vests led to a statistically significant increase in vest usage, the absolute increase was modest. Additional strategies beyond removing economic barriers are important to augment adherence to road safety behaviours for injury prevention.

Epidemiology of Coxiella burnetii infection in Africa: a OneHealth systematic review.

BACKGROUND: Q fever is a common cause of febrile illness and community-acquired pneumonia in resource-limited settings. Coxiella burnetii, the causative pathogen, is transmitted among varied host species, but the epidemiology of the organism in Africa is poorly understood. We conducted a systematic review of C. burnetii epidemiology in Africa from a "One Health" perspective to synthesize the published data and identify knowledge gaps. METHODS/PRINCIPAL FINDINGS: We searched nine databases to identify articles relevant to four key aspects of C. burnetii epidemiology in human and animal populations in Africa: infection prevalence; disease incidence; transmission risk factors; and infection control efforts. We identified 929 unique articles, 100 of which remained after full-text review. Of these, 41 articles describing 51 studies qualified for data extraction. Animal seroprevalence studies revealed infection by C. burnetii (≤13%) among cattle except for studies in Western and Middle Africa (18-55%). Small ruminant seroprevalence ranged from 11-33%. Human seroprevalence was <8% with the exception of studies among children and in Egypt (10-32%). Close contact with camels and rural residence were associated with increased seropositivity among humans. C. burnetii infection has been associated with livestock abortion. In human cohort studies, Q fever accounted for 2-9% of febrile illness hospitalizations and 1-3% of infective endocarditis cases. We found no studies of disease incidence estimates or disease control efforts. CONCLUSIONS/SIGNIFICANCE: C. burnetii infection is detected in humans and in a wide range of animal species across Africa, but seroprevalence varies widely by species and location. Risk factors underlying this variability are poorly understood as is the role of C. burnetii in livestock abortion. Q fever consistently accounts for a notable proportion of undifferentiated human febrile illness and infective endocarditis in cohort studies, but incidence estimates are lacking. C. burnetii presents a real yet underappreciated threat to human and animal health throughout Africa.

Evaluation of in-hospital management for febrile illness in Northern Tanzania before and after 2010 World Health Organization Guidelines for the treatment of malaria.

OBJECTIVE: In 2010, the World Health Organization (WHO) published updated guidelines emphasizing and expanding recommendations for a parasitological confirmation of malaria before treating with antimalarials. This study aimed to assess differences in historic (2007-2008) (cohort 1) and recent (2011-2012) (cohort 2) hospital cohorts in the diagnosis and treatment of febrile illness in a low malaria prevalence area of northern Tanzania. MATERIALS AND METHODS: We analyzed data from two prospective cohort studies that enrolled febrile adolescents and adults aged ≥13 years. All patients received quality-controlled aerobic blood cultures and malaria smears. We compared patients' discharge diagnoses, treatments, and outcomes to assess changes in the treatment of malaria and bacterial infections. RESULTS: In total, 595 febrile inpatients were enrolled from two referral hospitals in Moshi, Tanzania. Laboratory-confirmed malaria was detected in 13 (3.2%) of 402 patients in cohort 1 and 1 (0.5%) of 193 patients in cohort 2 (p = 0.041). Antimalarials were prescribed to 201 (51.7%) of 389 smear-negative patients in cohort 1 and 97 (50.5%) of 192 smear-negative patients in cohort 2 (p = 0.794). Bacteremia was diagnosed from standard blood culture in 58 (14.5%) of 401 patients in cohort 1 compared to 18 (9.5%) of 190 patients in cohort 2 (p = 0.091). In cohort 1, 40 (69.0%) of 58 patients with a positive blood culture received antibacterials compared to 16 (88.9%) of 18 patients in cohort 2 (p = 0.094). In cohort 1, 43 (10.8%) of the 399 patients with known outcomes died during hospitalization compared with 12 (6.2%) deaths among 193 patients in cohort 2 (p = 0.073). DISCUSSION: In a setting of low malaria transmission, a high proportion of smear-negative patients were diagnosed with malaria and treated with antimalarials despite updated WHO guidelines on malaria treatment. Improved laboratory diagnostics for non-malaria febrile illness might help to curb this practice.

A randomized controlled trial of standard versus intensified tuberculosis diagnostics on treatment decisions by physicians in Northern Tanzania.

BACKGROUND: Routine tuberculosis culture remains unavailable in many high-burden areas, including Tanzania. This study sought to determine the impact of providing mycobacterial culture results over standard of care [unconcentrated acid-fast (AFB) smears] on management of persons with suspected tuberculosis. METHODS: Adults and children with suspected tuberculosis were randomized to standard (direct AFB smear only) or intensified (concentrated AFB smear and tuberculosis culture) diagnostics and followed for 8 weeks. The primary endpoint was appropriate treatment (i.e. antituberculosis therapy for those with tuberculosis, no antituberculous therapy for those without tuberculosis). RESULTS: Seventy participants were randomized to standard (n = 37, 53%) or intensive (n = 33, 47%) diagnostics. At 8 weeks, 100% (n = 22) of participants in follow up randomized to intensive diagnostics were receiving appropriate care, vs. 22 (88%) of 25 participants randomized to standard diagnostics (p = 0.14). Overall, 18 (26%) participants died; antituberculosis therapy was associated with lower mortality (9% who received antiuberculosis treatment died vs. 26% who did not, p = 0.04). CONCLUSIONS: Under field conditions in a high burden setting, the impact of intensified diagnostics was blunted by high early mortality. Enhanced availability of rapid diagnostics must be linked to earlier access to care for outcomes to improve.

Seroprevalence of Hepatitis B and C Viruses Among Children in Kilimanjaro Region, Tanzania.

BACKGROUND: Data on human immunodeficiency virus (HIV) and hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection among children in Africa are limited. We evaluated the seroprevalence of both viruses among healthy, HIV-uninfected children and HIV-infected children in the Kilimanjaro region of northern Tanzania. METHODS: HBV and HCV markers were assessed using serum and plasma samples from HIV-negative children ages 1 month to 18 years, recruited primarily from 2 hospital vaccination clinics; and HIV-infected children 1-16 years of age, enrolled in care and on highly active antiretroviral therapy (HAART). HBV markers included hepatitis B surface antigen (HBsAg), hepatitis B surface antibody, and hepatitis B core antibody (HBcAb). Evidence of any prior HBV infection was defined as a single positive HBsAg or HBcAb result; presumed chronic hepatitis B infection was defined as a single positive HBsAg result. HCV infection was assessed by anti-HCV enzyme-linked immunosorbent assay. RESULTS: Samples from 547 children were tested. Of 157 children infected with HIV, 9.6% (95% CI: 4.9, 14.2) showed evidence of any HBV infection, compared to 2.1% (95% CI: .6, 3.5) of HIV-negative children. Children with HIV were much more likely to show evidence of HBV infection than children without HIV (odds ratio [OR] = 5.0, P < .0001). Prevalence of presumed chronic HBV infection was 2.9% (95% CI: 1.5, 4.3) overall. Again, prevalence was higher among HIV-infected children (7.0% [95% CI: 3.0, 11.0]) compared to HIV-negative children (1.3% [95% CI: .2, 2.4]; OR = 5.8 [P = .0003]). Of 546 samples tested for anti-HCV antibody, none were positive. CONCLUSION: HBV seroprevalence is high among children in the Kilimanjaro Region, with a significantly higher prevalence among children who are infected with HIV. Routine screening for HBV is needed among HIV-infected children. Patients with coinfection require closer monitoring of liver transaminases due to potential for hepatic toxicities, and they may need HAART regimens that will target both viruses. Guidelines for the management of coinfected children are urgently needed.

Comparing actual and perceived causes of fever among community members in a low malaria transmission setting in northern Tanzania.

OBJECTIVE: To compare actual and perceived causes of fever in northern Tanzania. METHODS: In a standardised survey, heads of households in 30 wards in Moshi, Tanzania, were asked to identify the most common cause of fever for children and for adults. Responses were compared to data from a local hospital-based fever aetiology study that used standard diagnostic techniques. RESULTS: Of 810 interviewees, the median (range) age was 48 (16, 102) years and 509 (62.8%) were women. Malaria was the most frequently identified cause of fever, cited by 353 (43.6%) and 459 (56.7%) as the most common cause of fever for children and adults, respectively. In contrast, malaria accounted for 8 (2.0%) of adult and 6 (1.3%) of paediatric febrile admissions in the fever aetiology study. Weather was the second most frequently cited cause of fever. Participants who identified a non-biomedical explanation such as weather as the most common cause of fever were more likely to prefer a traditional healer for treatment of febrile adults (OR 2.7, P < 0.001). Bacterial zoonoses were the most common cause of fever among inpatients, but no interviewees identified infections from animal contact as the most common cause of fever for adults; two (0.2%) identified these infections as the most common cause of fever for children. CONCLUSIONS: Malaria is perceived to be a much more common cause of fever than hospital studies indicate, whereas other important diseases are under-appreciated in northern Tanzania. Belief in non-biomedical explanations of fever is common locally and has important public health consequences.

Who tests, who doesn't, and why? Uptake of mobile HIV counseling and testing in the Kilimanjaro Region of Tanzania.

BACKGROUND: Optimally, expanded HIV testing programs should reduce barriers to testing while attracting new and high-risk testers. We assessed barriers to testing and HIV risk among clients participating in mobile voluntary counseling and testing (MVCT) campaigns in four rural villages in the Kilimanjaro Region of Tanzania. METHODS: Between December 2007 and April 2008, 878 MVCT participants and 506 randomly selected community residents who did not access MVCT were surveyed. Gender-specific logistic regression models were used to describe differences in socioeconomic characteristics, HIV exposure risk, testing histories, HIV related stigma, and attitudes toward testing between MVCT participants and community residents who did not access MVCT. Gender-specific logistic regression models were used to describe differences in socioeconomic characteristics, HIV exposure risk, testing histories, HIV related stigma, and attitudes toward testing, between the two groups. RESULTS: MVCT clients reported greater HIV exposure risk (OR 1.20 [1.04 to 1.38] for males; OR 1.11 [1.03 to 1.19] for females). Female MVCT clients were more likely to report low household expenditures (OR 1.47 [1.04 to 2.05]), male clients reported higher rates of unstable income sources (OR 1.99 [1.22 to 3.24]). First-time testers were more likely than non-testers to cite distance to testing sites as a reason for not having previously tested (OR 2.17 [1.05 to 4.48] for males; OR 5.95 [2.85 to 12.45] for females). HIV-related stigma, fears of testing or test disclosure, and not being able to leave work were strongly associated with non-participation in MVCT (ORs from 0.11 to 0.84). CONCLUSIONS: MVCT attracted clients with increased exposure risk and fewer economic resources; HIV related stigma and testing-related fears remained barriers to testing. MVCT did not disproportionately attract either first-time or frequent repeat testers. Educational campaigns to reduce stigma and fears of testing could improve the effectiveness of MVCT in attracting new and high-risk populations.

Community-acquired bloodstream infections in Africa: a systematic review and meta-analysis.

Data on the prevalence and causes of community-acquired bloodstream infections in Africa are scarce. We searched three databases for studies that prospectively studied patients admitted to hospital with at least a blood culture, and found 22 eligible studies describing 58 296 patients, of whom 2051 (13.5%) of 15 166 adults and 3527 (8.2%) of 43 130 children had bloodstream infections. 1643 (29.1%) non-malaria bloodstream infections were due to Salmonella enterica (58.4% of these non-typhoidal Salmonella), the most prevalent isolate overall and in adults, and 1031 (18.3% overall) were due to Streptococcus pneumoniae, the most common isolate in children. Other common isolates included Staphylococcus aureus (531 infections; 9.5%) and Escherichia coli (412; 7.3%). Mycobacterium tuberculosis complex accounted for 166 (30.7%) of 539 isolates in seven studies that used mycobacterial culture techniques. HIV infection was associated with any bloodstream infection, particularly with S enterica and M tuberculosis complex bacteraemia. Where recorded, patients with bloodstream infections had an in-hospital case fatality of 18.1%. Our results show that bloodstream infections are common and associated with high mortality. Improved clinical microbiology services and reassessment of empirical treatment guidelines that account for the epidemiology of bloodstream infections might contribute to better outcomes.

Predicting virologic failure among HIV-1-infected children receiving antiretroviral therapy in Tanzania: a cross-sectional study.

BACKGROUND: Many HIV care and treatment programs in resource-limited settings rely on clinical and immunologic monitoring of antiretroviral therapy (ART), but accuracy of this strategy to detect virologic failure (VF) among children has not been evaluated. METHODS: A cross-sectional sample of HIV-infected children aged 1-16 years on ART >or=6 months receiving care at a Tanzanian referral center underwent clinical staging, CD4 lymphocyte measurement, plasma HIV-1 RNA level, and complete blood count. Associations with VF (HIV-1 RNA >or=400 copies/mL) were determined utilizing bivariable and multivariate analyses; accuracy of current clinical and immunologic guidelines in identifying children with VF was assessed. FINDINGS: Of 206 children (median age 8.7 years, ART duration 2.4 years), 65 (31.6%) demonstrated VF at enrollment. Clinical and immunological criteria identified 2 (3.5%) of 57 children with VF on first-line therapy, exhibiting 3.5% sensitivity and 100% specificity. VF was associated with younger age, receipt of nevirapine vs. efavirenz-based regimen, CD4% < 25%, and physician documentation of maladherence (P < 0.05 on bivariable analysis); the latter 2 factors remained significant on multivariate logistic regression. INTERPRETATION: This study demonstrates poor performance of clinical and immunologic criteria in identifying children with virologic failure. Affordable techniques for measuring HIV-1 RNA level applicable in resource-limited settings are urgently needed.