Choice of antiretroviral therapy has low impact on weight gain.

OBJECTIVE: Antiretroviral therapy (ART) containing integrase inhibitors (INSTIs) and/or tenofovir alafenamide (TAF) has been associated with greater weight gain. Yet few studies have delineated between exposure to "anchor" drugs (protease inhibitors [PI], non-nucleoside reverse transcriptase inhibitors [NNRTI] or INSTIs) and exposure to nucleoside reverse transcriptase inhibitors (NRTIs). DESIGN: In this cohort of antiretroviral (ARV) naïve patients who initiated ART from 2008-2022, we analyzed body mass index (BMI) gain for 8 contemporary "anchor" drugs and 3 contemporary NRTIs during the first 3 years of ART. We censored patients if they stopped, switched, or added another ARV to their regimen. METHODS: We used generalized estimating equations (GEE) to assess the association between BMI gain and choice of ART and a non-linear mixed model for the marginal coefficients of determination. We adjusted for time, baseline demographic and HIV-characteristics, and time-updated HIV and substance use related variables. RESULTS: 4,194 patients contributed 20,528 BMI measurements which were used for multivariable modeling. Most patients were black (55%) and male (77%). Median BMI gain over 3 years was +1.9 kg/m2 (IQR 0.1-4.1). ARV use accounted for only 9% of the predicted BMI change. Only efavirenz (EFV) and tenofovir disoproxil fumarate (TDF) were independently associated with (lower) weight gain while no differences between INSTIs, PIs, or rilpivirine were observed, nor between TAF and abacavir. CONCLUSIONS: The choice of initial ART had little impact on weight gain. INSTIs or TAF were not independently associated with weight change after ART initiation, but EFV and TDF were.

Advanced HIV disease in East Africa and Nigeria, in The African Cohort Study.

BACKGROUND: Earlier antiretroviral therapy (ART) may decrease progression to advanced HIV disease (AHD) with CD4 count of <200 cells per cubic millimeter or clinical sequelae. We assessed factors associated with AHD among people living with HIV before and during the "test and treat" era. SETTING: The African Cohort Study prospectively enrolls adults with and without HIV from 12 clinics in Uganda, Kenya, Tanzania, and Nigeria. METHODS: Enrollment evaluations included clinical history, physical examination, and laboratory testing. Generalized estimating equations were used to estimate adjusted odds ratios and 95% confidence intervals for factors associated with CD4 count of <200 cells per cubic millimeter at study visits. RESULTS: From 2013 to 2021, 3059 people living with HIV with available CD4 at enrollment were included; median age was 38 years [interquartile range: 30-46 years], and 41.3% were men. From 2013 to 2021, the prevalence of CD4 count of <200 cells per cubic millimeter decreased from 10.5% to 3.1%, whereas the percentage on ART increased from 76.6% to 100% ( P <0.001). Factors associated with higher odds of CD4 count of <200 cells per cubic millimeter were male sex (adjusted odds ratio 1.56 [confidence interval: 1.29 to 1.89]), being 30-39 years (1.42 [1.11-1.82]) or older (compared with <30), have World Health Organization stage 2 disease (1.91 [1.48-2.49]) or higher (compared with stage 1), and HIV diagnosis eras 2013-2015 (2.19 [1.42-3.37]) or later (compared with <2006). Compared with ART-naive, unsuppressed participants, being viral load suppressed on ART, regardless of ART duration, was associated with lower odds of CD4 count of <200 cells per cubic millimeter (<6 months on ART: 0.45 [0.34-0.58]). CONCLUSION: With ART scale-up, AHD has declined. Efforts targeting timely initiation of suppressive ART may further reduce AHD risk.

Assessing sex differences in viral load suppression and reported deaths using routinely collected program data from PEPFAR-supported countries in sub-Saharan Africa.

BACKGROUND: In sub-Saharan Africa, more women than men access HIV testing and treatment and may have better viral load suppression (VLS). We utilized routinely reported aggregated HIV program data from 21 sub-Saharan African countries to examine sex differences in VLS and death rates within antiretroviral therapy (ART) programs supported by the United States President's Emergency Plan for AIDS Relief (PEPFAR). METHODS: We included VLS and reported death data for persons aged 15 + years on ART from October-December 2020 disaggregated by sex and age for each subnational unit (SNU). We used linear mixed-model regression to estimate VLS proportion and negative binomial mixed-model regression to estimate the rates of death and death plus interruptions in treatment (IIT). All models were weighted for SNU-level ART population size and adjusted for sex, age, HIV/tuberculosis coinfection, country, and SNU; models for reported deaths and deaths plus IIT were also adjusted for SNU-level VLS. RESULTS: Mean VLS proportion was higher among women than men (93.0% vs. 92.0%, p-value < 0.0001) and 50 + than 15-49 age group (93.7% vs. 91.2%, p-value < 0.0001). The mean rate of reported deaths was higher among men than women (2.37 vs. 1.51 per 1000 persons, p-value < 0.0001) and 50 + than 15-49 age group (2.39 vs. 1.50 per 1000, p-value < 0.0001); the mean rate of reported deaths plus IIT was higher among men (30.1 in men vs. 26.0 in women per 1000, p-value < 0.0001) and higher among 15-49 than 50 + age group (34.7 vs. 22.6 per 1000, p-value < 0.0001). CONCLUSIONS: The mean rate of reported deaths was higher among men in most models despite adjusting for VLS. Further exploration into differences in care-seeking behaviors; coverage of screening, prophylaxis, and/or treatment of opportunistic infections; and more extensive testing options for men to include CD4 is recommended.

Rapid antiretroviral therapy initiation in patients with advanced HIV disease: 6-month outcomes of an observational cohort evaluation in Lesotho.

For adults and adolescents, the World Health Organization defines advanced HIV disease (AHD) as a CD4 (cluster of differentiation 4) count of <200 cells/mm3 or a clinical stage 3 or 4 event. We describe clinical outcomes in a cohort of AHD patients at two regional hospitals in Lesotho. From November 2018-June 2019, we prospectively enrolled eligible patients (≥15 years) not on antiretroviral therapy (ART) presenting with WHO-defined AHD into a differentiated model of care for AHD (including rapid ART initiation) and followed them for six months. All patients received Tuberculosis (TB) symptom screening with further diagnostic testing; serum cryptococcal antigen (CrAg) screening was done for CD4 <100 cells/mm3 or WHO clinical stage 3 or 4. Medical record data were abstracted using visit checklist forms. Categorical and continuous variables were summarized using frequencies, percentages, and means, respectively. Kaplan-Meier was used to estimate survival. Of 537 HIV-positive patients screened, 150 (27.9%) had AHD of which 109 were enrolled. Mean age was 38 years and 62 (56.9%) were men. At initial clinic visit, 8 (7.3%) were already on treatment and 33% (36/109) had presumptive TB per symptom screening. Among 39/109 (40.2%) patients screened for CrAg at initial visit, five (12.8%) were CrAg-positive. Among 109 enrolled, 77 (70.6%) initiated ART at their initial clinic visit, while 32 delayed ART initiation (median delay: 14 days). Of the 109 participants enrolled, 76 (69.7%) completed the 6-month follow-up, 17 (15.6%) were lost to follow-up, 5 (4.6%) transferred to other health facilities and 11 (10.1%) died. The 6-month survival was 87.4%; among 74 patients with a viral load result, 6-month viral suppression (<1,000 copies/ml) was 85.1%. Our study found that even after the implementation of Test and Treat of ART in 2016 in Lesotho, over 25% of patients screened had AHD. Patients with AHD had a high prevalence of TB and CrAg positivity, underscoring the need to assess for AHD and rapidly initiate ART within a package of AHD care for optimal patient outcomes.

Modelling the impact of CD4 testing on mortality from TB and cryptococcal meningitis among patients with advanced HIV disease in nine countries.

INTRODUCTION: Despite antiretroviral therapy (ART) scale-up among people living with HIV (PLHIV), those with advanced HIV disease (AHD) (defined in adults as CD4 count <200 cells/mm3 or clinical stage 3 or 4), remain at high risk of death from opportunistic infections. The shift from routine baseline CD4 testing towards viral load testing in conjunction with "Test and Treat" has limited AHD identification. METHODS: We used official estimates and existing epidemiological data to project deaths from tuberculosis (TB) and cryptococcal meningitis (CM) among PLHIV-initiating ART with CD4 <200 cells/mm3 , in the absence of select World Health Organization recommended diagnostic or therapeutic protocols for patients with AHD. We modelled the reduction in deaths, based on the performance of screening/diagnostic testing and the coverage and efficacy of treatment/preventive therapies for TB and CM. We compared projected TB and CM deaths in the first year of ART from 2019 to 2024, with and without CD4 testing. The analysis was performed for nine countries: South Africa, Kenya, Lesotho, Mozambique, Nigeria, Uganda, Zambia, Zimbabwe and the Democratic Republic of Congo. RESULTS: The effect of CD4 testing comes through increased identification of AHD and consequent eligibility for protocols for AHD prevention, diagnosis and management; algorithms for CD4 testing avert between 31% and 38% of deaths from TB and CM in the first year of ART. The number of CD4 tests required per death averted varies widely by country from approximately 101 for South Africa to 917 for Kenya. CONCLUSIONS: This analysis supports retaining baseline CD4 testing to avert deaths from TB and CM, the two most deadly opportunistic infections among patients with AHD. However, national programmes will need to weigh the cost of increasing CD4 access against other HIV-related priorities and allocate resources accordingly.

Tuberculosis treatment within differentiated service delivery models in global HIV/TB programming.

INTRODUCTION: Providing more convenient and patient-centred options for service delivery is a priority within global HIV programmes. These efforts improve patient satisfaction and retention and free up time for providers to focus on new HIV diagnoses or severe illness. Recently, the coronavirus disease 2019 (COVID-19) pandemic precipitated expanded eligibility criteria for these differentiated service delivery (DSD) models to decongest clinics and protect patients and healthcare workers. This has resulted in dramatic scale-up of DSD for antiretroviral therapy, cotrimoxazole and tuberculosis (TB) preventive treatment. While TB treatment among people living with HIV (PLHIV) has traditionally involved frequent, facility-based management, TB treatment can also be adapted within DSD models. Such adaptations could include electronic tools to ensure appropriate clinical management, treatment support, adherence counselling and adverse event (AE) monitoring. In this commentary, we outline considerations for DSD of TB treatment among PLHIV, building on best practices from global DSD model implementation for HIV service delivery. DISCUSSION: In operationalizing TB treatment in DSD models, we consider the following: what activity is being done, when or how often it takes place, where it takes place, by whom and for whom. We discuss considerations for various programme elements including TB screening and diagnosis; medication dispensing; patient education, counselling and support; clinical management and monitoring; and reporting and recording. General approaches include multi-month dispensing for TB medications during intensive and continuation phases of treatment and standardized virtual adherence and AE monitoring. Lastly, we provide operational examples of TB treatment delivery through DSD models, including a conceptual model and an early implementation experience from Zambia. CONCLUSIONS: COVID-19 has catalysed the rapid expansion of differentiated patient-centred service delivery for PLHIV. Expanding DSD models to include TB treatment can capitalize on existing platforms, while providing high-quality, routine treatment, follow-up and patient education and empowerment.

Addressing advanced HIV disease and mortality in global HIV programming.

INTRODUCTION: The US President's Emergency Plan for AIDS Relief (PEPFAR) was launched to increase access to antiretroviral treatment (ART) among people living with HIV (PLHIV) and to prevent new HIV infections globally. As new infections have decreased in many PEPFAR-supported countries, PEPFAR is increasingly focusing on understanding and decreasing mortality among PLHIV, specifically by addressing advanced HIV disease (AHD) and its attendant opportunistic infections (OIs). Several developments in identifying AHD, in preventing, diagnosing, and treating selected OIs, and in PEPFAR's support for mortality surveillance make this an opportune moment for PEPFAR to address HIV-related mortality. DISCUSSION: AHD upon diagnosis or re-engagement in HIV care is not uncommon, and it substantially increases risk of death from OIs. The World Health Organization provides evidence-based guidelines for a package of interventions for preventing, diagnosing, and treating common OIs, including tuberculosis (TB), cryptococcal meningitis, and severe bacterial infections. PEPFAR facilitates implementation of these guidelines. To identify PLHIV with low CD4, PEPFAR plans to support expanded access to CD4 testing, including a point-of-care assay that differentiates CD4 cell count as a binary of greater than or less than 200 cells/µL. To prevent AHD-related mortality, PEPFAR supports rapid ART initiation with integrase inhibitor-based regimens and implementation and documentation of TB preventive treatment. To diagnose selected OIs, PEPFAR is implementing urine lateral flow lipoarabinomannan use to identify TB among PLHIV who have a CD4 cell count < 200 cells/µL. To treat selected OIs, PEPFAR has focused on improving patient-centered care in TB/HIV co-infection services and scaling up implementation of new drug regimens for cryptococcal meningitis. To better understand mortality, PEPFAR has introduced an indicator, TX_ML, to routinely and systematically categorize outcomes, including deaths, among PLHIV on ART. CONCLUSIONS: PEPFAR is increasing its efforts to identify AHD; to prevent, diagnose, and treat OIs; and to track mortality in its programs. These ongoing efforts, done in collaboration with other stakeholders, seek to decrease mortality among PLHIV.

Loss to follow-up before and after initiation of antiretroviral therapy in HIV facilities in Lilongwe, Malawi.

INTRODUCTION: Although several studies have explored factors associated with loss to follow-up (LTFU) from HIV care, there remains a gap in understanding how these factors vary by setting, volume of patient and patients' demographic and clinical characteristics. We determined rates and factors associated with LTFU in HIV care Lilongwe, Malawi. METHODS: We conducted a retrospective cohort study of HIV-infected individuals aged 15 years or older at the time of registration for HIV care in 12 ART facilities, between April 2012 and March 2013. HIV-positive individuals who had not started ART (pre-ART patients) were clinically assessed to determine ART eligibility at registration and during clinic follow-up visits. ART-eligible patients were initiated on triple antiretroviral combination. Study data were abstracted from patients' cards, facility ART registers or electronic medical record system from the date of registration for HIV care to a maximum follow-up period of 24 months. Descriptive statistics were undertaken to summarize characteristics of the study patients. Separate univariable and multivariable poisson regression models were used to explore factors associated with LTFU in pre-ART and ART care. RESULTS: A total of 10,812 HIV-infected individuals registered for HIV care. Of these patients, 1,907 (18%) and 8,905 (82%) enrolled in pre-ART and ART care, respectively. Of the 1,907 pre-ART patients, 490 (26%) subsequently initiated ART and were included in both the pre-ART and ART analyses. The LTFU rates among patients in pre-ART and ART care were 48 and 26 per 100 person-years, respectively. Of the 9,105 ART patients with reasons for starting ART, 2,451 (27%) were initiated on ART because of pregnancy or breastfeeding (Option B+) status. Multivariable analysis showed that being ≥35 years and female were associated with decreased risk of LTFU in the pre-ART and ART phases of HIV care. However, being in WHO clinical stage 3 (adjusted risk ratio (aRR) 1.35, 95% confidence interval (CI): 1.20-1.51) and stage 4 (aRR 1.87, 95% CI: 1.62-2.18), body mass index ≤ 18.4 (aRR 1.24, 95% CI: 1.11-1.39) at ART initiation, poor adherence to clinic appointments (aRR 4.55, 95% CI: 4.16-4.97) and receiving HIV care in rural facilities (aRR 2.32, 95% CI: 1.94-2.87) were associated with increased risk of LTFU among ART patients. Being re-initiated on ART once (aRR 0.20, 95% CI: 0.17-0.22), more than once (aRR 0.06, 95% CI: 0.05-0.07), and being enrolled at a low-volume facility (aRR 0.25, 95% CI: 0.20-0.30) were associated with decreased risk of LTFU from ART care. CONCLUSION: A sizeable proportion of ART LTFU occurred among women enrolled during pregnancy or breast-feeding. Non- compliance to clinic and receiving ART in a rural facility or high-volume facility were associated with increased risk of LTFU from ART care. Developing effective interventions that target high-risk subgroups and contexts may help reduce LTFU from HIV care.

Trends in Prevalence of Advanced HIV Disease at Antiretroviral Therapy Enrollment - 10 Countries, 2004-2015.

Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/µL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.*,†,§ To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence.

Oseltamivir Use Among Children and Adults Hospitalized With Community-Acquired Pneumonia.

BACKGROUND: Data on oseltamivir treatment among hospitalized community-acquired pneumonia (CAP) patients are limited. METHODS: Patients hospitalized with CAP at 6 hospitals during the 2010-2012 influenza seasons were included. We assessed factors associated with oseltamivir treatment using logistic regression. RESULTS: Oseltamivir treatment was provided to 89 of 1627 (5%) children (<18 years) and 143 of 1051 (14%) adults. Among those with positive clinician-ordered influenza tests, 39 of 61 (64%) children and 37 of 48 (77%) adults received oseltamivir. Among children, oseltamivir treatment was associated with hospital A (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 1.36-4.88), clinician-ordered testing performed (aOR, 2.44; 95% CI, 1.47-5.19), intensive care unit (ICU) admission (aOR, 2.09; 95% CI, 1.27-3.45), and age ≥2 years (aOR, 1.43; 95% CI, 1.16-1.76). Among adults, oseltamivir treatment was associated with clinician-ordered testing performed (aOR, 8.38; 95% CI, 4.64-15.12), hospitals D and E (aOR, 3.46-5.11; 95% CI, 1.75-11.01), Hispanic ethnicity (aOR, 2.06; 95% CI, 1.18-3.59), and ICU admission (aOR, 2.05; 95% CI, 1.34-3.13). CONCLUSIONS: Among patients hospitalized with CAP during influenza season, oseltamivir treatment was moderate overall and associated with clinician-ordered testing, severe illness, and specific hospitals. Increased clinician education is needed to include influenza in the differential diagnosis for hospitalized CAP patients and to test and treat patients empirically if influenza is suspected.

Outbreak of Middle East Respiratory Syndrome at Tertiary Care Hospital, Jeddah, Saudi Arabia, 2014.

During March-May 2014, a Middle East respiratory syndrome (MERS) outbreak occurred in Jeddah, Saudi Arabia, that included many persons who worked or received medical treatment at King Fahd General Hospital. We investigated 78 persons who had laboratory-confirmed MERS during March 2-May 10 and documented contact at this hospital. The 78 persons with MERS comprised 53 patients, 16 healthcare workers, and 9 visitors. Among the 53 patients, the most probable sites of acquisition were the emergency department (22 patients), inpatient areas (17), dialysis unit (11), and outpatient areas (3). Infection control deficiencies included limited separation of suspected MERS patients, patient crowding, and inconsistent use of infection control precautions; aggressive improvements in these deficiencies preceded a decline in cases. MERS coronavirus transmission probably was multifocal, occurring in multiple hospital settings. Continued vigilance and strict application of infection control precautions are necessary to prevent future MERS outbreaks.

Benefit of Early Initiation of Influenza Antiviral Treatment to Pregnant Women Hospitalized With Laboratory-Confirmed Influenza.

BACKGROUND: We describe the impact of early initiation of influenza antiviral treatment among pregnant women hospitalized with laboratory-confirmed influenza during the 2010-2014 influenza seasons. METHODS: Severe influenza was defined as illness with ≥1 of the following: intensive care unit admission, need for mechanical ventilation, respiratory failure, pulmonary embolism, sepsis, or death. Within severity stratum, we used parametric survival analysis to compare length of stay by timing of antiviral treatment, adjusting for underlying conditions, influenza vaccination, and pregnancy trimester. RESULTS: Among 865 pregnant women, the median age was 27 years (interquartile range [IQR], 23-31 years). Most (68%) were healthy, and 85% received antiviral treatment. Sixty-three women (7%) had severe influenza, and 4 died. Severity was associated with preterm delivery and fetal loss. Women with severe influenza were less likely to be vaccinated than those without severe influenza (14% vs 26%; P = .03). Among women treated with antivirals ≤2 days versus those treated >2 days from illness onset, the median length of stay was 2.2 days (interquartile range [IQR], 0.9-5.8 days; n = 8) versus 7.8 days (IQR, 3.0-20.6 days; n = 7), respectively, for severe influenza (P = .03) and 2.4 days (IQR, 2.3-2.5 days; n = 153) versus 3.1 days (IQR, 2.8-3.5 days; n = 62), respectively, for nonsevere influenza (P < .01). CONCLUSIONS: Early initiation of influenza antiviral treatment to pregnant women hospitalized with influenza may reduce the length of stay, especially among those with severe influenza. Influenza during pregnancy is associated with maternal and infant morbidity, and annual influenza vaccination is warranted.

Association of Higher MERS-CoV Virus Load with Severe Disease and Death, Saudi Arabia, 2014.

Middle East respiratory syndrome coronavirus (MERS-CoV) causes a spectrum of illness. We evaluated whether cycle threshold (Ct) values (which are inversely related to virus load) were associated with clinical severity in patients from Saudi Arabia whose nasopharyngeal specimens tested positive for this virus by real-time reverse transcription PCR. Among 102 patients, median Ct of 31.0 for the upstream of the E gene target for 41 (40%) patients who died was significantly lower than the median of 33.0 for 61 survivors (p=0.0087). In multivariable regression analyses, risk factors for death were age>60 years), underlying illness, and decreasing Ct for each 1-point decrease in Ct). Results were similar for a composite severe outcome (death and/or intensive care unit admission). More data are needed to determine whether modulation of virus load by therapeutic agents affects clinical outcomes.

Hospitalizations and Deaths Because of Respiratory and Diarrheal Diseases Among Haitian Children Under Five Years of Age, 2011-2013.

BACKGROUND: Respiratory and diarrheal diseases are leading causes of morbidity and mortality among children younger than 5 years in developing countries. Data on the burden of these diseases in Haiti are scarce. METHODS: We conducted a retrospective review of hospital admission registries during January 1, 2011-December 31, 2013 for children younger than 5 years in 6 hospitals in Haiti. We recorded the number of all-cause, respiratory and diarrheal disease admissions and deaths by epidemiologic week and age. RESULTS: A total of 31,565 hospital admissions and 1763 deaths were recorded among children aged <5 years during the study period. Respiratory diseases accounted for 9183 (29%) hospitalizations and 301 (17%) deaths. Children aged 6-23 months had the highest percentage of hospitalizations attributable to respiratory diseases (38%), whereas children aged 36-47 months had the highest proportion of deaths attributable to respiratory diseases (37%). Respiratory disease hospitalizations followed a bimodal seasonal pattern, with peaks during May-June and October-December. Diarrheal diseases accounted for 8063 (26%) hospitalizations and 224 (13%) deaths. Children aged 6-11 months had the highest percentage of diarrhea-associated hospitalizations (39%) and deaths (29%). Diarrheal disease admissions peaked in January-April before the rainy season. CONCLUSIONS: Respiratory and diarrheal diseases contributed to more than half of hospitalizations and almost a third of deaths in children younger than 5 years in Haiti. These data are essential to assess the impact of pneumococcal and rotavirus vaccines and other interventions in Haiti.

2014 MERS-CoV outbreak in Jeddah--a link to health care facilities.

BACKGROUND: A marked increase in the number of cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred in Jeddah, Saudi Arabia, in early 2014. We evaluated patients with MERS-CoV infection in Jeddah to explore reasons for this increase and to assess the epidemiologic and clinical features of this disease. METHODS: We identified all cases of laboratory-confirmed MERS-CoV infection in Jeddah that were reported to the Saudi Arabian Ministry of Health from January 1 through May 16, 2014. We conducted telephone interviews with symptomatic patients who were not health care personnel, and we reviewed hospital records. We identified patients who were reported as being asymptomatic and interviewed them regarding a history of symptoms in the month before testing. Descriptive analyses were performed. RESULTS: Of 255 patients with laboratory-confirmed MERS-CoV infection, 93 died (case fatality rate, 36.5%). The median age of all patients was 45 years (interquartile range, 30 to 59), and 174 patients (68.2%) were male. A total of 64 patients (25.1%) were reported to be asymptomatic. Of the 191 symptomatic patients, 40 (20.9%) were health care personnel. Among the 151 symptomatic patients who were not health care personnel, 112 (74.2%) had data that could be assessed, and 109 (97.3%) of these patients had had contact with a health care facility, a person with a confirmed case of MERS-CoV infection, or someone with severe respiratory illness in the 14 days before the onset of illness. The remaining 3 patients (2.7%) reported no such contacts. Of the 64 patients who had been reported as asymptomatic, 33 (52%) were interviewed, and 26 of these 33 (79%) reported at least one symptom that was consistent with a viral respiratory illness. CONCLUSIONS: The majority of patients in the Jeddah MERS-CoV outbreak had contact with a health care facility, other patients, or both. This highlights the role of health care-associated transmission. (Supported by the Ministry of Health, Saudi Arabia, and by the U.S. Centers for Disease Control and Prevention.).

Identification of molecular markers associated with alteration of receptor-binding specificity in a novel genotype of highly pathogenic avian influenza A(H5N1) viruses detected in Cambodia in 2013.

Human infections with influenza A(H5N1) virus in Cambodia increased sharply during 2013. Molecular characterization of viruses detected in clinical specimens from human cases revealed the presence of mutations associated with the alteration of receptor-binding specificity (K189R, Q222L) and respiratory droplet transmission in ferrets (N220K with Q222L). Discovery of quasispecies at position 222 (Q/L), in addition to the absence of the mutations in poultry/environmental samples, suggested that the mutations occurred during human infection and did not transmit further.

The impact of combined antiretroviral therapy on biologic false-positive rapid plasma reagin serologies in a longitudinal cohort of HIV-infected persons.

BACKGROUND: Our objective was to determine the impact of combination antiretroviral therapy (cART) and the degree of immunosuppression on biologic false-positive (BFP) rapid plasma reagin (RPR) tests among persons infected with human immunodeficiency virus (HIV). METHODS: This was a nested retrospective study of HIV-infected patients enrolled in the Johns Hopkins HIV Clinical Cohort. BFP RPR was defined as a reactive RPR and a nonreactive fluorescent treponemal antibody-absorption (FTA-ABS) test. Patients with BFP tests were compared to 2 control groups: HIV-infected patients (1) with active syphilis (reactive RPR and FTA-ABS) and (2) without current syphilis (nonreactive RPR). A persistent BFP test was defined by having at least 2 visits with consistent BFP at all visits. RESULTS: Of 711 patients with HIV, 96 (13.5%) had BFP tests and 342 (48.1%) had syphilis. Twenty-two of 96 (23%) had persistent BFP tests. cART use was associated with decreased odds of BFP tests compared to having syphilis (adjusted odds ratio [AOR], 0.31; 95% CI, .15-.63) and those with nonreactive RPR (AOR, 0.42; 95% CI, .22-.81). cART use was also associated with decreased odds of BFP persistence (AOR, 0.07; 95% CI, .01-.33). Neither CD4 count nor HIV RNA was significantly associated with BFP test results. Lower RPR titers, younger age, and injection drug use were associated with increased odds of BFP. CONCLUSIONS: The use of cART appears to decrease the odds of BFP RPR tests. This finding suggests that nontreponemal titer fluctuations in persons with HIV may reflect the influence of factors unrelated to syphilis disease activity.

Tenofovir use and urinary biomarkers among HIV-infected women in the Women's Interagency HIV Study (WIHS).

BACKGROUND: Tenofovir (TDF) has been associated with renal tubular injury. Biomarkers that signal early tubular dysfunction are needed because creatinine rise lags behind TDF-associated kidney dysfunction. We examined several urinary biomarkers to determine if rises accompanying TDF initiation preceded creatinine changes. METHODS: Three urinary biomarkers of tubular impairment--neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-ß-D-glucosaminidase (NAG), and ß-2-microglobulin (ß2MG)--were measured across 3 time points (one pre-TDF visit and 2 post-TDF visits) in 132 HIV-positive women from the Women's Interagency HIV Study. Women initiating highly active antiretroviral therapy (HAART) containing TDF were propensity score matched to women initiating HAART without TDF and women not on HAART. RESULTS: There were no differences between groups for NGAL or NAG, but ß2MG was 19 times more likely to be elevated among TDF users at the second post-TDF visit compared with non-TDF users at the pre-TDF visit (P < 0.01). History of proteinuria was associated with elevated NGAL (P < 0.01). Factors associated with elevated NAG were glomerular filtration rate <60 mL/minute, history of proteinuria, hepatitis C (P < 0.01 for all), and diabetes mellitus (P = 0.05). Factors associated with increased odds of elevated ß2MG were HIV RNA >100,000 copies/mL, hepatitis C, boosted protease inhibitor use, and glomerular filtration rate <60 mL/minute (P ≤ 0.01 for all). CONCLUSIONS: ß2MG levels are elevated in women on TDF, indicating probable early renal dysfunction. Biomarker elevation is additionally associated with baseline chronic kidney disease, uncontrolled viremia, and boosted protease inhibitor use. Future studies are needed to explore urinary biomarker thresholds in identifying treated HIV-infected individuals at risk for renal dysfunction.

Clinical factors associated with plasma F2-isoprostane levels in HIV-infected adults.

PURPOSE: Oxidant stress may be an effect of antiretroviral therapy (ART) or chronic HIV infection. Plasma F2-isoprostanes (F2-IsoP) reflect lipid peroxidation and oxidant stress and have been described in ART-associated toxicities. We explored factors associated with F2-IsoP in HIV-infected adults. METHODS: HIV-infected adults enrolled in this cross-sectional study were (a) on ART including zidovudine or stavudine but not non-nucleoside reverse transcriptase inhibitors (NNRTI), (b) on ART including NNRTI, or (c) not on ART. Plasma F2-IsoP levels were quantified by GC/MS, and clinical and laboratory data were collected at enrollment. RESULTS: Among 285 participants, 24% were female, 37% were African American, and 194 (68%) were on ART; 44 (23%) of whom were receiving efavirenz, 45 (23%) nevirapine, and 85 (44%) protease inhibitors. Median F2-IsoP was lower in those on NNRTI than those on ART without NNRTI (p = .02). In a multivariable model, factors independently associated with increased F2-IsoP were female sex (p = .002), higher BMI (p = .01), and heavy smoking (p = .004). There was a trend toward lower F2-IsoP among nevirapine users (p = .054). CONCLUSIONS: Among HIV-infected adults, oxidant stress status differs by sex, BMI, smoking status, and perhaps specific ART. Prospective studies should better define relationships between oxidant stress and complications of HIV infection and its therapy.