Publications by authors named "Ingrid V Bassett"

99 Publications

Prevalence and risk factors for hypertension and diabetes among those screened in a refugee settlement in Uganda.

Confl Health 2021 Jul 5;15(1):53. Epub 2021 Jul 5.

Department of Emergency Medicine, University of Washington, Seattle, WA, USA.

Background: Diabetes and hypertension are increasingly prevalent in low and middle income countries, but they are not well documented in refugee settlements in these settings. We sought to estimate the prevalence and associated characteristics of diabetes and hypertension among adults presenting for clinic-based HIV testing in Nakivale Refugee Settlement in Uganda.

Methods: HIV-negative adults presenting to outpatient clinics for HIV testing at three health centers in Nakivale Refugee Settlement were enrolled from January 2019 through January 2020. Multi-lingual research assistants administered questionnaires aloud to ascertain medical history and sociodemographic information. The research assistants used standardized procedures to measure participants' blood pressure to detect hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg), and conduct a point-of-care blood glucose test for diabetes (random blood glucose ≥11.1 mmol/L with self-reported frequent urination or thirst, or fasting blood glucose ≥7.0 mmol/L regardless of symptoms), as per Uganda Ministry of Health guidelines. We used χ-square or Fisher's exact test to test for differences in disease prevalence by refugee status and log-binomial or Poisson regression models to estimate associations of immigration status and country of origin, respectively, with hypertension and diabetes while controlling for age, sex, education level, and body mass index.

Results: Among 2127 participants, 1379 (65%) were refugees or asylum seekers and 748 (35%) were Ugandan nationals. Overall, 32 participants met criteria for diabetes (1.5%, 95% CI 1.1-2.1%) and the period prevalence was 2.3% (95% CI 1.7-3.0). There were 1067 (50%, 95% CI 48.0-52.2%) who met the criteria for pre-hypertension and 189 (9%, 95% CI 7.7-10.1%) for hypertension. These proportions did not vary by immigration status or country of origin in univariate tests or multivariable regression models.

Conclusions: Hypertension was common and diabetes was uncommon among those screened in a Ugandan refugee settlement. Routine blood pressure screening should be considered in this setting. Additional research could develop diabetes screening criteria to help identify at risk individuals in this limited resource setting.
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http://dx.doi.org/10.1186/s13031-021-00388-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256510PMC
July 2021

Medical Mistrust and Stigma Associated with COVID-19 Among People Living with HIV in South Africa.

AIDS Behav 2021 May 17. Epub 2021 May 17.

Division of Infectious Diseases, Massachusetts General Hospital, Boston, USA.

We evaluated COVID-19 stigma and medical mistrust among people living with HIV in South Africa. We conducted telephone interviews with participants in a prospective study of a decentralized antiretroviral therapy program. Scales assessing medical mistrust, conspiracy beliefs, anticipated and internalized stigma, and stereotypes specific to COVID-19 were adapted primarily from the HIV literature, with higher scores indicating more stigma or mistrust. Among 303 participants, the median stigma summary score was 4 [interquartile range (IQR) 0-8; possible range 0-24] and 6 (IQR 2-9) for mistrust (possible range 0-28). A substantial proportion of participants agreed or strongly agreed with at least one item assessing stigma (54%) or mistrust (43%). Higher COVID-19 stigma was associated with female gender and antecedent HIV stigma, and lower stigma with reporting television as a source of information on COVID-19. Further efforts should focus on effects of stigma and mistrust on protective health behaviors and vaccine hesitancy.
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http://dx.doi.org/10.1007/s10461-021-03307-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127851PMC
May 2021

Laboratory Reflex and Clinic-Based Point-of-Care Cryptococcal Antigen Screening for Preventing Meningitis and Mortality Among People Living With HIV.

J Acquir Immune Defic Syndr 2021 Aug;87(5):1205-1213

Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Introduction: Cryptococcosis remains a leading cause of meningitis and mortality among people living with HIV (PLHIV) worldwide. We sought to evaluate laboratory-based cryptococcal antigen (CrAg) reflex testing and a clinic-based point-of-care (POC) CrAg screening intervention for preventing meningitis and mortality among PLHIV in South Africa.

Methods: We conducted a prospective pre-post intervention study of adults presenting for HIV testing in Umlazi township, South Africa, over a 6-year period (2013-2019). Participants were enrolled during 3 phases of CrAg testing: CrAg testing ordered by a clinician (clinician-directed testing, 2013-2015); routine laboratory-based CrAg reflex testing for blood samples with CD4 ≤100 cells/mm3 (laboratory reflex testing, 2015-2017); and a clinic-based intervention with POC CD4 testing and POC CrAg testing for PLHIV with CD4 ≤200 cells/mm3 with continued standard-of-care routine laboratory reflex testing among those with CD4 ≤100 cells/mm3 (clinic-based testing, 2017-2019). The laboratory and clinical teams performed serum CrAg by enzyme immunoassay and lateral flow assay (Immy Diagnostics, Norman, OK). We followed up participants for up to 14 months to compare associations between baseline CrAg positivity, antiretroviral therapy and fluconazole treatment initiation, and outcomes of cryptococcal meningitis, hospitalization, and mortality.

Results: Three thousand one hundred five (39.4%) of 7877 people screened were HIV-positive, of whom 908 had CD4 ≤200 cells/mm3 and were included in the analyses. Laboratory reflex and clinic-based testing increased CrAg screening (P < 0.001) and diagnosis of CrAg-positive PLHIV (P = 0.011). When compared with clinician-directed testing, clinic-based CrAg testing showed an increase in the number of PLHIV diagnosed with cryptococcal meningitis (4.5% vs. 1.5%; P = 0.059), initiation of fluconazole preemptive therapy (7.2% vs. 2.5%; P = 0.010), and initiation of antiretroviral therapy (96.8% vs. 91.3%; P = 0.012). Comparing clinic-based testing with laboratory reflex testing, there was no significant difference in the cumulative incidence of cryptococcal meningitis (4.5% vs. 4.1%; P = 0.836) or mortality (8.1% vs. 9.9%; P = 0.557).

Conclusions: Laboratory reflex and clinic-based CrAg testing facilitated the diagnosis of HIV-associated cryptococcosis and fluconazole initiation but did not reduce cryptococcal meningitis or mortality. In this nonrandomized cohort, clinical outcomes were similar between laboratory reflex testing and clinic-based POC CrAg testing.
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http://dx.doi.org/10.1097/QAI.0000000000002717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263484PMC
August 2021

Urban sexual health clinic patients with 'undetermined risk' for HIV are less likely to receive PrEP.

Sex Transm Dis 2021 May 1. Epub 2021 May 1.

Division of Infectious Diseases, Massalrpchusetts General Hospital, Boston, MA Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA Harvard Medical School, Boston, MA Harvard University Center for AIDS Research, Harvard University, Boston, MA.

Background: New diagnoses of HIV increasingly occur among people who fall outside traditional transmission risk categories. This group remains poorly defined and HIV prevention efforts for this group lag behind efforts for patients in other risk groups.

Methods: We conducted a retrospective review of patient visits at sexual health clinics in Boston, Massachusetts over a 14-month period. Patients were classified into CDC-defined HIV transmission risk categories. We compared frequencies of STIs, HIV, PrEP indications, and PrEP prescriptions. Predictors of HIV or STI among patients in the undetermined risk category were assessed with logistic regression.

Results: There were 4723 clinic visits during the study period. Patients in the undetermined risk group constituted the largest proportion (55.8%), followed by men who have sex with men (MSM) (42.7%). The proportion of visits by patients in the undetermined risk group with an indication for PrEP was low (28.0%) compared to MSM (91.3%) and MSM who also inject drugs (93.8%), however, the absolute number was high (737). Among patients with an indication for PrEP, those in the undetermined risk group were least likely to receive a prescription. Behavioral risk factors were poorly predictive of STI or HIV among patients in the undetermined risk group.

Conclusion: Patients with undetermined risk for HIV constituted a large proportion of clinic visits and had a large volume of sexual health needs but rarely received PrEP when indicated. To end the HIV epidemic in the US, prevention efforts must include people who fall outside traditional risk categories.
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http://dx.doi.org/10.1097/OLQ.0000000000001460DOI Listing
May 2021

Sex differences in inflammatory markers in patients hospitalized with COVID-19 infection: Insights from the MGH COVID-19 patient registry.

PLoS One 2021 28;16(4):e0250774. Epub 2021 Apr 28.

From the Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, United States of America.

Background: Men are at higher risk for serious complications related to COVID-19 infection than women. More robust immune activation in women has been proposed to contribute to decreased disease severity, although systemic inflammation has been associated with worse outcomes in COVID-19 infection. Whether systemic inflammation contributes to sex differences in COVID-19 infection is not known.

Study Design And Methods: We examined sex differences in inflammatory markers among 453 men (mean age 61) and 328 women (mean age 62) hospitalized with COVID-19 infection at the Massachusetts General Hospital from March 8 to April 27, 2020. Multivariable linear regression models were used to examine the association of sex with initial and peak inflammatory markers. Exploratory analyses examined the association of sex and inflammatory markers with 28-day clinical outcomes using multivariable logistic regression.

Results: Initial and peak CRP were higher in men compared with women after adjustment for baseline differences (initial CRP: ß 0.29, SE 0.07, p = 0.0001; peak CRP: ß 0.31, SE 0.07, p<0.0001) with similar findings for IL-6, PCT, and ferritin (p<0.05 for all). Men had greater than 1.5-greater odds of dying compared with women (OR 1.71, 95% CI 1.04-2.80, p = 0.03). Sex modified the association of peak CRP with both death and ICU admission, with stronger associations observed in men compared with women (death: OR 9.19, 95% CI 4.29-19.7, p <0.0001 in men vs OR 2.81, 95% CI 1.52-5.18, p = 0.009 in women, Pinteraction = 0.02).

Conclusions: In a sample of 781 men and women hospitalized with COVID-19 infection, men exhibited more robust inflammatory activation as evidenced by higher initial and peak inflammatory markers, as well as worse clinical outcomes. Better understanding of sex differences in immune responses to COVID-19 infection may shed light on the pathophysiology of COVID-19 infection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250774PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081177PMC
May 2021

Health Worker Perspectives on Barriers and Facilitators of Assisted Partner Notification for HIV for Refugees and Ugandan Nationals: A Mixed Methods Study in West Nile Uganda.

AIDS Behav 2021 Apr 21. Epub 2021 Apr 21.

Departments of Emergency Medicine and Global Health, University of Washington, Seattle, WA, USA.

Assisted partner notification (APN) is recommended by the World Health Organization to notify sexual partners of HIV exposure. Since 2018, APN has been offered in Uganda to Ugandan nationals and refugees. Distinct challenges faced by individuals in refugee settlements may influence APN utilization and effectiveness. To explore APN barriers and facilitators, we extracted index client and sexual partner data from APN registers at 11 health centers providing care to refugees and Ugandan nationals in West Nile Uganda and conducted qualitative interviews with health workers (N = 32). Since APN started, 882 index clients participated in APN identifying 1126 sexual partners. Following notification, 95% (1025/1126) of partners tested for HIV; 22% (230/1025) were diagnosed with HIV with 14% (139/1025) of tested partners newly diagnosed. Fear of stigma and disclosure-related violence limit APN utilization and effectiveness. Prospective research involving index clients and sexual partners is needed to facilitate safe APN optimization in refugee settlements.
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http://dx.doi.org/10.1007/s10461-021-03265-1DOI Listing
April 2021

Placental decidual arteriopathy and vascular endothelial growth factor A (VEGF-A) expression among women with and without HIV.

J Infect Dis 2021 Apr 21. Epub 2021 Apr 21.

Massachusetts General Hospital Department of Pathology, Boston, MA, USA.

Background: Women with HIV (WHIV) are at higher risk of adverse birth outcomes. Proposed mechanisms for the increased risk include placental arteriopathy (vasculopathy) and maternal vascular malperfusion (MVM) due to antiretroviral therapy (ART) and medical comorbidities. However, these features and their underlying pathophysiologic mechanisms have not been well characterized in WHIV.

Methods: We performed gross and histologic examination and immunohistochemistry staining for vascular endothelial growth factor A (VEGF-A), a key angiogenic factor, on placentas from women with one or more MVM risk factors including: weight <5 th percentile, histologic infarct or distal villous hypoplasia, nevirapine-based ART, hypertension, and pre-eclampsia/eclampsia during pregnancy. We compared pathologic characteristics by maternal HIV serostatus.

Results: A total of 27/41 (66%) placentas assessed for VEGF-A were from WHIV. Mean maternal age was 27 years. Among WHIV, median CD4 T-cell count was 440 cells/mm 3 and HIV viral load was undetectable in 74%. Of VEGF-A stained placentas, both decidua and villous endothelium tissue layers were present in 36 (88%). VEGF-A was detected in 31/36 (86%) with decidua present, and 39/40 (98%) with villous endothelium present. There were no differences in VEGF-A presence in any tissue type by maternal HIV serostatus (P=0.28-1.0). MVM was more common in placentas selected for VEGF-A staining (51 versus 8%, P<0.001).

Conclusions: VEGF-A immunostaining was highly prevalent, and staining pattern did not differ by maternal HIV serostatus among those with MVM risk factors, indicating the role of VEGF-A in placental vasculopathy may not differ by maternal HIV serostatus.
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http://dx.doi.org/10.1093/infdis/jiab201DOI Listing
April 2021

Beyond T Staging in the "Treat-All" Era: Severity and Heterogeneity of Kaposi Sarcoma in East Africa.

J Acquir Immune Defic Syndr 2021 Aug;87(5):1119-1127

University of California, San Francisco, CA.

Background: Although many patients with Kaposi sarcoma (KS) in sub-Saharan Africa are diagnosed with AIDS Clinical Trials Group (ACTG) T1 disease, T1 staging insufficiently captures clinical heterogeneity of advanced KS. Using a representative community-based sample, we detailed disease severity at diagnosis to inform KS staging and treatment in sub-Saharan Africa.

Methods: We performed rapid case ascertainment on people living with HIV, aged 18 years or older, newly diagnosed with KS from 2016 to 2019 at 3 clinic sites in Kenya and Uganda to ascertain disease stage as close as possible to diagnosis. We reported KS severity using ACTG and WHO staging criteria and detailed measurements that are not captured in the current staging systems.

Results: We performed rapid case ascertainment within 1 month for 241 adults newly diagnosed with KS out of 389 adult patients with suspected KS. The study was 68% men with median age 35 years and median CD4 count 239. Most of the patients had advanced disease, with 82% qualifying as ACTG T1 and 64% as WHO severe/symptomatic KS. The most common ACTG T1 qualifiers were edema (79%), tumor-associated ulceration (24%), extensive oral KS (9%), pulmonary KS (7%), and gastrointestinal KS (4%). There was marked heterogeneity within T1 KS, with 25% of patients having 2 T1 qualifying symptoms and 3% having 3 or more.

Conclusion: Most of the patients newly diagnosed with KS had advanced stage disease, even in the current antiretroviral therapy "treat-all" era. We observed great clinical heterogeneity among advanced stage patients, leading to questions about whether all patients with advanced KS require the same treatment strategy.
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http://dx.doi.org/10.1097/QAI.0000000000002699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263487PMC
August 2021

Modeling Adherence Interventions Among Youth with HIV in the United States: Clinical and Economic Projections.

AIDS Behav 2021 Feb 6. Epub 2021 Feb 6.

Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

The Adolescent Medicine Trials Network for HIV/AIDS Interventions is evaluating treatment adherence interventions (AI) to improve virologic suppression (VS) among youth with HIV (YWH). Using a microsimulation model, we compared two strategies: standard-of-care (SOC) and a hypothetical 12-month AI that increased cohort-level VS in YWH in care by an absolute ten percentage points and cost $100/month/person. Projected outcomes included primary HIV transmissions, deaths and life-expectancy, lifetime HIV-related costs, and incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year [QALY]). Compared to SOC, AI would reduce HIV transmissions by 15% and deaths by 12% at 12 months. AI would improve discounted life expectancy/person by 8 months at an added lifetime cost/person of $5,300, resulting in an ICER of $7,900/QALY. AI would be cost-effective at $2,000/month/person or with efficacies as low as a 1 percentage point increase in VS. YWH-targeted adherence interventions with even modest efficacy could improve life expectancy, prevent onward HIV transmissions, and be cost-effective.
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http://dx.doi.org/10.1007/s10461-021-03169-0DOI Listing
February 2021

The role of obesity in inflammatory markers in COVID-19 patients.

Obes Res Clin Pract 2021 Jan-Feb;15(1):96-99. Epub 2020 Dec 23.

The Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, United States; Division of Cardiology, Massachusetts General Hospital, Boston, MA, United States. Electronic address:

Obesity has emerged as a significant risk factor for severe COVID-19 worldwide. Given both COVID-19 infection and obesity have been associated with increased systemic inflammation, we evaluated inflammatory markers in obese and non-obese individuals hospitalized for COVID-19 at Massachusetts General Hospital. We hypothesized that obese patients would have a more exuberant inflammatory response as evidenced by higher initial and peak inflammatory markers along with worse clinical outcomes. Of the 781 patients, 349 were obese (45%). Obese individuals had higher initial and peak levels of CRP and ESR as well as higher peak d-dimer (P < 0.01 for all) in comparison to non-obese individuals, while. IL-6 and ferritin were similar. In addition, obese individuals had a higher odds of requiring vasopressor use (OR 1.54, 95% CI 1.00-2.38, P = 0.05), developing hypoxemic respiratory failure (OR 1.58, 95% CI 1.04-2.40, P = 0.03) and death (OR 2.20, 95% CI 1.31-3.70, P = 0.003) within 28 days of presentation to care. Finally, higher baseline levels of CRP and D-dimer were associated with worse clinical outcomes even after adjustment for BMI. Our findings suggest greater disease severity in obese individuals is characterized by more exuberant inflammation.
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http://dx.doi.org/10.1016/j.orcp.2020.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833898PMC
February 2021

Massachusetts general hospital Covid-19 registry reveals two distinct populations of hospitalized patients by race and ethnicity.

PLoS One 2020 22;15(12):e0244270. Epub 2020 Dec 22.

Harvard Medical School, Boston, Massachusetts, United States of America.

Objective: To evaluate differences by race/ethnicity in clinical characteristics and outcomes among hospitalized patients with Covid-19 at Massachusetts General Hospital (MGH).

Methods: The MGH Covid-19 Registry includes confirmed SARS-CoV-2-infected patients hospitalized at MGH and is based on manual chart reviews and data extraction from electronic health records (EHRs). We evaluated differences between White/Non-Hispanic and Hispanic patients in demographics, complications and 14-day outcomes among the N = 866 patients hospitalized with Covid-19 from March 11, 2020-May 4, 2020.

Results: Overall, 43% of patients hospitalized with Covid-19 were women, median age was 60.4 [IQR = (48.2, 75)], 11.3% were Black/non-Hispanic and 35.2% were Hispanic. Hispanic patients, representing 35.2% of patients, were younger than White/non-Hispanic patients [median age 51y; IQR = (40.6, 61.6) versus 72y; (58.0, 81.7) (p<0.001)]. Hispanic patients were symptomatic longer before presenting to care (median 5 vs 3d, p = 0.039) but were more likely to be sent home with self-quarantine than be admitted to hospital (29% vs 16%, p<0.001). Hispanic patients had fewer comorbidities yet comparable rates of ICU or death (34% vs 36%). Nonetheless, a greater proportion of Hispanic patients recovered by 14 days after presentation (62% vs 45%, p<0.001; OR = 1.99, p = 0.011 in multivariable adjusted model) and fewer died (2% versus 18%, p<0.001).

Conclusions: Hospitalized Hispanic patients were younger and had fewer comorbidities compared to White/non-Hispanic patients; despite comparable rates of ICU care or death, a greater proportion recovered. These results have implications for public health policy and the design and conduct of clinical trials.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244270PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755195PMC
January 2021

"You are not alone": a qualitative study to explore barriers to ART initiation and implications for a proposed community-based youth treatment club among young adults newly diagnosed with HIV in South Africa.

AIDS Care 2021 07 21;33(7):952-961. Epub 2020 Dec 21.

Harvard Medical School, Boston, MA, USA.

In South Africa, despite universal antiretroviral therapy (ART) availability, 60% of persons living with HIV (PLWH) ages 15-24 are not on treatment. This qualitative study aimed to identify barriers to ART initiation and the implications for a proposed community-based Youth Treatment Club to improve ART initiation for young PLWH in limited-resource, high HIV-prevalence communities in Cape Town, South Africa. Recruiting participants at community testing sites from 2018 to 2019, we conducted semi-structured interviews, informed by Social Action Theory (SAT), with 20 young adults, ages 18- to 24-years-old, newly diagnosed with HIV, along with 10 healthcare providers. Through systematic qualitative analysis, we found that young PLWH face barriers to treatment initiation in three SAT domains: (1) stigmatizing social norms (social regulation processes); (2) challenges coping with a new diagnosis (self-regulation processes); and (3) anticipated stigma in the clinic environment (contextual factors). Participants shared that a proposed community-based Youth Treatment Club for newly diagnosed youth would be an acceptable strategy to promote ART initiation. They emphasized that it should include supportive peers, trained facilitator support for counseling and education, and a youth-friendly environment.
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http://dx.doi.org/10.1080/09540121.2020.1861179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215080PMC
July 2021

Understanding the role of interpersonal violence in assisted partner notification for HIV: a mixed-methods study in refugee settlements in West Nile Uganda.

J Glob Health 2020 Dec;10(2):020440

Departments of Emergency Medicine and Global Health, University of Washington, Seattle, Washington, USA.

Background: Assisted partner notification (APN) for HIV was introduced in refugee settlements in West Nile Uganda in 2018 to facilitate testing of sexual partners. While APN is an effective strategy recommended by the World Health Organization, its safety has not been evaluated in a refugee settlement context in which participants have high prior exposure to interpersonal violence. The extent to which interpersonal violence influences APN utilization and the frequency with which post-APN interpersonal violence occurs remains unknown.

Methods: To explore the relationship between APN and interpersonal violence, a cross-sectional mixed-methods study was conducted at 11 health centers in refugee settlements in West Nile Uganda. Routinely collected index client and sexual partner data were extracted from APN registers and semi-structured interviews were conducted with health workers.

Results: Through APN, 1126 partners of 882 distinct index clients were identified. For 8% (75/958) of partners, index clients reported a history of intimate partner violence (IPV). For 20% (226/1126) of partners, index clients were screened for post-APN IPV; 8 cases were reported of which 88% (7/8) concerned partners with whom index clients reported prior history of IPV. In qualitative interviews (N = 32), health workers reported HIV disclosure-related physical, sexual and psychological violence and deprivation or neglect. Incidents of disclosure-related violence against health workers and dependents of index clients were also reported. Fear of disclosure-related violence was identified as a major barrier to APN that prevents index clients from listing sexual partners.

Conclusions: Incidents of interpersonal violence have been reported following HIV-disclosure and fear of interpersonal violence strongly influences APN participation. Addressing HIV perception and stigma may contribute to APN uptake and program safety. Prospective research on interpersonal violence involving index clients and sexual partners in refugee settlements is needed to facilitate safe engagement in APN for this vulnerable population.
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http://dx.doi.org/10.7189/jogh.10.020440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719270PMC
December 2020

A Social-Ecological Framework to Understand Barriers to HIV Clinic Attendance in Nakivale Refugee Settlement in Uganda: a Qualitative Study.

AIDS Behav 2021 Jun 2;25(6):1729-1736. Epub 2020 Dec 2.

Center for Global Health, Massachusetts General Hospital, Boston, MA, USA.

The social-ecological model proposes that efforts to modify health behaviors are influenced by constraints and facilitators at multiple levels. We conducted semi-structured interviews with 47 clients in HIV care and 8 HIV clinic staff to explore how such constraints and facilitators (individual, social environment, physical environment, and policies) affect engaging in HIV clinical care in Nakivale Refugee Settlement in Uganda. Thematic analysis revealed that participants were motivated to attend the HIV clinic because of the perceived quality of services and the belief that antiretroviral therapy improves health. Barriers to clinic attendance included distance, cost, unemployment, and climate. Those that disclosed their status had help in overcoming barriers to HIV care. Nondisclosure and stigma disrupted community support in overcoming these obstacles. Interventions to facilitate safe disclosure, mobilize social support, and provide more flexible HIV services may help overcome barriers to HIV care in this setting.
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http://dx.doi.org/10.1007/s10461-020-03102-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081685PMC
June 2021

A cohort study to assess a communication intervention to improve linkage to HIV care in Nakivale Refugee Settlement, Uganda.

Glob Public Health 2020 Nov 21:1-8. Epub 2020 Nov 21.

Department of Medicine, Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA.

Communication interventions to enhance linkage to HIV care have been successful in sub-Saharan Africa but have not been assessed among refugees. Refugees and Ugandan nationals participating in HIV testing in Nakivale Refugee Settlement were offered weekly phone call and short message service (SMS) reminders. We assessed linkage to care and predictors of linkage within 90 days of testing, comparing Intervention participants to those unwilling or ineligible to participate (Non-Intervention). Of 208 individuals diagnosed with HIV, 101 (49%) participated in the intervention. No difference existed between Intervention and Non-intervention groups in linkage to care (73 [72%] vs. 76 [71%],  = 0.88). Excluding those who linked prior to receipt of intervention, the intervention improved linkage (69 [68%] vs. 50 [47%],  = 0.002). Participants were more likely to link if they were older (aOR 2.39 [1.31, 4.37],  = 0.005) or Ugandan nationals (aOR 3.76 [1.12, 12.66],  = 0.033). Although the communication intervention did not significantly improve linkage to HIV care, the linkage was improved when excluding those with same-day linkage. Excluding participants without a phone was a significant limitation; these data are meant to inform more rigorous designs moving forward. Innovative methods to improve linkage to HIV care for this vulnerable population are urgently needed.
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http://dx.doi.org/10.1080/17441692.2020.1847310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137716PMC
November 2020

COVID-19 severity in hospitalized patients with asthma: A matched cohort study.

J Allergy Clin Immunol Pract 2021 01 22;9(1):497-500. Epub 2020 Oct 22.

Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, Mass; Clinical Epidemiology Program, Mongan Institute, Department of Medicine, Massachusetts General Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.

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http://dx.doi.org/10.1016/j.jaip.2020.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580590PMC
January 2021

Changing contextual factors from baseline to 9-months post-HIV diagnosis predict 5-year mortality in Durban, South Africa.

AIDS Care 2020 Nov 2:1-8. Epub 2020 Nov 2.

Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA.

Changes in an individual's contextual factors following HIV diagnosis may influence long-term outcomes. We evaluated how changes to contextual factors between HIV diagnosis and 9-month follow-up predict 5-year mortality among HIV-infected individuals in Durban, South Africa enrolled in the Sizanani Trial (NCT01188941). We used random survival forests to identify 9-month variables and changes from baseline predictive of time to mortality. We incorporated these into a Cox proportional hazards model including age, sex, and starting ART by 9 months , 9-month social support and competing needs, and changes in mental health between baseline and 9 months. Among 1,154 participants with South African ID numbers, 900 (78%) had baseline and 9-month data available of whom 109 (12%) died after 9-month follow-up. Those who reported less social support at 9 months had a 16% higher risk of mortality. Participants who went without basic needs or healthcare at 9 months had a 2.6 times higher hazard of death compared to participants who did not. Low social support and competing needs at 9-month follow-up substantially increase long-term mortality risk. Reassessing contextual factors during follow-up and targeting interventions to increase social support and affordability of care may reduce long-term mortality for HIV-infected individuals in South Africa.
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http://dx.doi.org/10.1080/09540121.2020.1837338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088454PMC
November 2020

The Treatment Ambassador Program: A Highly Acceptable and Feasible Community-Based Peer Intervention for South Africans Living with HIV Who Delay or Discontinue Antiretroviral Therapy.

AIDS Behav 2021 Apr 30;25(4):1129-1143. Epub 2020 Oct 30.

Health Services and Outcomes Research, Children's Mercy Kansas City, Kansas City, MO, USA.

We conducted a novel pilot randomized controlled trial of the Treatment Ambassador Program (TAP), an 8-session, peer-based, behavioral intervention for people with HIV (PWH) in South Africa not on antiretroviral therapy (ART). PWH (43 intervention, 41 controls) completed baseline, 3- and 6-month assessments. TAP was highly feasible (90% completion), with peer counselors demonstrating good intervention fidelity. Post-intervention interviews showed high acceptability of TAP and counselors, who supported autonomy, assisted with clinical navigation, and provided psychosocial support. Intention-to-treat analyses indicated increased ART initiation by 3 months in the intervention vs. control arm (12.2% [5/41] vs. 2.3% [1/43], Fisher exact p-value = 0.105; Cohen's h = 0.41). Among those previously on ART (off for > 6 months), 33.3% initiated ART by 3 months in the intervention vs. 14.3% in the control arm (Cohen's h = 0.45). Results suggest that TAP was highly acceptable and feasible among PWH not on ART.
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http://dx.doi.org/10.1007/s10461-020-03063-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979476PMC
April 2021

CoVA: An Acuity Score for Outpatient Screening that Predicts Coronavirus Disease 2019 Prognosis.

J Infect Dis 2021 01;223(1):38-46

Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Background: We sought to develop an automatable score to predict hospitalization, critical illness, or death for patients at risk for coronavirus disease 2019 (COVID-19) presenting for urgent care.

Methods: We developed the COVID-19 Acuity Score (CoVA) based on a single-center study of adult outpatients seen in respiratory illness clinics or the emergency department. Data were extracted from the Partners Enterprise Data Warehouse, and split into development (n = 9381, 7 March-2 May) and prospective (n = 2205, 3-14 May) cohorts. Outcomes were hospitalization, critical illness (intensive care unit or ventilation), or death within 7 days. Calibration was assessed using the expected-to-observed event ratio (E/O). Discrimination was assessed by area under the receiver operating curve (AUC).

Results: In the prospective cohort, 26.1%, 6.3%, and 0.5% of patients experienced hospitalization, critical illness, or death, respectively. CoVA showed excellent performance in prospective validation for hospitalization (expected-to-observed ratio [E/O]: 1.01; AUC: 0.76), for critical illness (E/O: 1.03; AUC: 0.79), and for death (E/O: 1.63; AUC: 0.93). Among 30 predictors, the top 5 were age, diastolic blood pressure, blood oxygen saturation, COVID-19 testing status, and respiratory rate.

Conclusions: CoVA is a prospectively validated automatable score for the outpatient setting to predict adverse events related to COVID-19 infection.
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http://dx.doi.org/10.1093/infdis/jiaa663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665643PMC
January 2021

Brief Report: Chronic Placental Inflammation Among Women Living With HIV in Uganda.

J Acquir Immune Defic Syndr 2020 11;85(3):320-324

Pathology, Massachusetts General Hospital, Boston, MA.

Background: HIV-exposed, uninfected (HEU) children have poorer early-life outcomes than HIV-unexposed children. The determinants of adverse health outcomes among HEU children are poorly understood but may result from chronic placental inflammation (CPI).

Setting And Methods: We enrolled 176 pregnant women living with HIV (WLWH) taking antiretroviral therapy in southwestern Uganda and 176 HIV-uninfected women to compare CPI prevalence by maternal HIV serostatus. Placentas were evaluated histologically by an expert pathologist for presence of CPI, defined as chronic chorioamnionitis, plasma cell deciduitis, villitis of unknown etiology, or chronic histiocytic intervillositis. Placentas with CPI were additionally immunostained with CD3 (T cell), CD20 (B cell), and CD68 (macrophage) markers to characterize inflammatory cell profiles.

Results: WLWH and HIV-uninfected women had similar age, parity, and gestational age. Among WLWH, the mean CD4 count was 480 cells/µL, and 74% had an undetectable HIV viral load. We detected CPI in 16 (9%) placentas from WLWH and 24 (14%) from HIV-uninfected women (P = 0.18). Among WLWH, CPI was not associated with the CD4 count or HIV viral load. Villitis of unknown etiology was twice as common among HIV-uninfected women than WLWH (10 vs. 5%, P = 0.04). Among placentas with CPI, more villous inflammatory cells stained for CD3 or CD68 among HIV-uninfected women than WLWH (79% vs. 46%, P = 0.07).

Conclusions: CPI prevalence did not differ by HIV serostatus. T-cell (CD3) and macrophage (CD68) markers were more prevalent in placental inflammatory cells from HIV-uninfected women. Our results do not support CPI as a leading mechanism for poor outcomes among HEU children in the antiretroviral therapy era.
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http://dx.doi.org/10.1097/QAI.0000000000002446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668230PMC
November 2020

Identifying and predicting longitudinal trajectories of care for people newly diagnosed with HIV in South Africa.

PLoS One 2020 21;15(9):e0238975. Epub 2020 Sep 21.

Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.

Background: Predicting long-term care trajectories at the time of HIV diagnosis may allow targeted interventions. Our objective was to uncover distinct CD4-based trajectories and determine baseline demographic, clinical, and contextual factors associated with trajectory membership.

Methods: We used data from the Sizanani trial (NCT01188941), in which adults were enrolled prior to HIV testing in Durban, South Africa from August 2010-January 2013. We ascertained CD4 counts from the National Health Laboratory Service over 5y follow-up. We used group-based statistical modeling to identify groups with similar CD4 count trajectories and Bayesian information criteria to determine distinct CD4 trajectories. We evaluated baseline factors that predict membership in specific trajectories using multinomial logistic regression. We examined calendar year of participant enrollment, age, gender, cohabitation, TB positivity, self-identified barriers to care, and ART initiation within 3 months of diagnosis.

Results: 688 participants had longitudinal data available. Group-based trajectory modeling identified four distinct trajectories: one with consistently low CD4 counts (21%), one with low CD4 counts that increased over time (22%), one with moderate CD4 counts that remained stable (41%), and one with high CD4 counts that increased over time (16%). Those with higher CD4 counts at diagnosis were younger, less likely to have TB, and less likely to identify barriers to care. Those in the least favorable trajectory (consistently low CD4 count) were least likely to start ART within 3 months.

Conclusions: One-fifth of people newly-diagnosed with HIV presented with low CD4 counts that failed to rise over time. Less than 40% were in a trajectory characterized by increasing CD4 counts. Patients in more favorable trajectories were younger, less likely to have TB, and less likely to report barriers to healthcare. Better understanding barriers to early care engagement and ART initiation will be necessary to improve long-term clinical outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238975PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505419PMC
October 2020

Diabetes as a Risk Factor for Poor Early Outcomes in Patients Hospitalized With COVID-19.

Diabetes Care 2020 12 26;43(12):2938-2944. Epub 2020 Aug 26.

Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA.

Objective: Diabetes and obesity are highly prevalent among hospitalized patients with coronavirus disease 2019 (COVID-19), but little is known about their contributions to early COVID-19 outcomes. We tested the hypothesis that diabetes is a risk factor for poor early outcomes, after adjustment for obesity, among a cohort of patients hospitalized with COVID-19.

Research Design And Methods: We used data from the Massachusetts General Hospital (MGH) COVID-19 Data Registry of patients hospitalized with COVID-19 between 11 March 2020 and 30 April 2020. Primary outcomes were admission to the intensive care unit (ICU), need for mechanical ventilation, and death within 14 days of presentation to care. Logistic regression models were adjusted for demographic characteristics, obesity, and relevant comorbidities.

Results: Among 450 patients, 178 (39.6%) had diabetes-mostly type 2 diabetes. Among patients with diabetes versus patients without diabetes, a higher proportion was admitted to the ICU (42.1% vs. 29.8%, respectively, = 0.007), required mechanical ventilation (37.1% vs. 23.2%, = 0.001), and died (15.9% vs. 7.9%, = 0.009). In multivariable logistic regression models, diabetes was associated with greater odds of ICU admission (odds ratio 1.59 [95% CI 1.01-2.52]), mechanical ventilation (1.97 [1.21-3.20]), and death (2.02 [1.01-4.03]) at 14 days. Obesity was associated with greater odds of ICU admission (2.16 [1.20-3.88]) and mechanical ventilation (2.13 [1.14-4.00]) but not with death.

Conclusions: Among hospitalized patients with COVID-19, diabetes was associated with poor early outcomes, after adjustment for obesity. These findings can help inform patient-centered care decision making for people with diabetes at risk for COVID-19.
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http://dx.doi.org/10.2337/dc20-1506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770271PMC
December 2020

Pediatric Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Clinical Presentation, Infectivity, and Immune Responses.

J Pediatr 2020 12 20;227:45-52.e5. Epub 2020 Aug 20.

Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA.

Objectives: As schools plan for re-opening, understanding the potential role children play in the coronavirus infectious disease 2019 (COVID-19) pandemic and the factors that drive severe illness in children is critical.

Study Design: Children ages 0-22 years with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presenting to urgent care clinics or being hospitalized for confirmed/suspected SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) at Massachusetts General Hospital were offered enrollment in the Massachusetts General Hospital Pediatric COVID-19 Biorepository. Enrolled children provided nasopharyngeal, oropharyngeal, and/or blood specimens. SARS-CoV-2 viral load, ACE2 RNA levels, and serology for SARS-CoV-2 were quantified.

Results: A total of 192 children (mean age, 10.2 ± 7.0 years) were enrolled. Forty-nine children (26%) were diagnosed with acute SARS-CoV-2 infection; an additional 18 children (9%) met the criteria for MIS-C. Only 25 children (51%) with acute SARS-CoV-2 infection presented with fever; symptoms of SARS-CoV-2 infection, if present, were nonspecific. Nasopharyngeal viral load was highest in children in the first 2 days of symptoms, significantly higher than hospitalized adults with severe disease (P = .002). Age did not impact viral load, but younger children had lower angiotensin-converting enzyme 2 expression (P = .004). Immunoglobulin M (IgM) and Immunoglobulin G (IgG) to the receptor binding domain of the SARS-CoV-2 spike protein were increased in severe MIS-C (P < .001), with dysregulated humoral responses observed.

Conclusions: This study reveals that children may be a potential source of contagion in the SARS-CoV-2 pandemic despite having milder disease or a lack of symptoms; immune dysregulation is implicated in severe postinfectious MIS-C.
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http://dx.doi.org/10.1016/j.jpeds.2020.08.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438214PMC
December 2020

COVID-19 Outpatient Screening: a Prediction Score for Adverse Events.

medRxiv 2020 Jun 22. Epub 2020 Jun 22.

Background: We sought to develop an automatable score to predict hospitalization, critical illness, or death in patients at risk for COVID-19 presenting for urgent care during the Massachusetts outbreak.

Methods: Single-center study of adult outpatients seen in respiratory illness clinics (RICs) or the emergency department (ED), including development (n = 9381, March 7-May 2) and prospective (n = 2205, May 3-14) cohorts. Data was queried from Partners Enterprise Data Warehouse. Outcomes were hospitalization, critical illness or death within 7 days. We developed the COVID-19 Acuity Score (CoVA) using automatically extracted data from the electronic medical record and learning-to-rank ordinal logistic regression modeling. Calibration was assessed using predicted-to-observed event ratio (E/O). Discrimination was assessed by C-statistics (AUC).

Results: In the development cohort, 27.3%, 7.2%, and 1.1% of patients experienced hospitalization, critical illness, or death, respectively; and in the prospective cohort, 26.1%, 6.3%, and 0.5%. CoVA showed excellent performance in the development cohort (concurrent validation) for hospitalization (E/O: 1.00, AUC: 0.80); for critical illness (E/O: 1.00, AUC: 0.82); and for death (E/O: 1.00, AUC: 0.87). Performance in the prospective cohort (prospective validation) was similar for hospitalization (E/O: 1.01, AUC: 0.76); for critical illness (E/O 1.03, AUC: 0.79); and for death (E/O: 1.63, AUC=0.93). Among 30 predictors, the top five were age, diastolic blood pressure, blood oxygen saturation, COVID-19 testing status, and respiratory rate.

Conclusions: CoVA is a prospectively validated automatable score to assessing risk for adverse outcomes related to COVID-19 infection in the outpatient setting.
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http://dx.doi.org/10.1101/2020.06.17.20134262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325189PMC
June 2020

Accuracy of Resident-Performed Point-of-Care Lung Ultrasound Examinations Versus Chest Radiography in Pneumothorax Follow-up After Tube Thoracostomy in Rwanda.

J Ultrasound Med 2020 Mar 6;39(3):499-506. Epub 2019 Sep 6.

Department of Emergency Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Objectives: The aim of this study was to evaluate the accuracy and timeliness of resident-performed point-of-care lung ultrasound (LUS) examinations for the follow-up of pneumothorax (PTX) after tube thoracostomy.

Methods: After brief training, Rwandan surgical residents blinded to chest radiography (CXR) performed and interpreted LUS examinations for PTX in participants undergoing CXR for PTX follow-up. Treating clinicians interpreted CXR for the presence of PTX for therapeutic decisions. Lung ultrasound was later reviewed by ultrasound experts, and CXR was reviewed by a radiologist. We defined expert LUS interpretation as the reference standard. The sensitivity and specificity of resident-performed LUS examinations for diagnosing PTX were calculated. We assessed agreement between trained resident versus expert LUS and clinician versus radiology CXR using the Cohen κ coefficient. We compared the time to results between LUS and CXR.

Results: Over an 8-month period, 51 participants were enrolled. Compared to expert LUS interpretation, the sensitivity and specificity (95% confidence intervals) of resident LUS were 100% (85%-100%) and 96% (82%-100%), respectively, whereas the sensitivity and specificity of clinician-interpreted CXR were 48% (27%-69%) and 100% (88%-100%). The agreement between resident and expert LUS was excellent (κ = 0.96), whereas the agreement between clinician and radiologist CXR was only moderate (κ = 0.60). The time to results was significantly longer for CXR than LUS (mean, 1335 versus 396 minutes; P = .0001).

Conclusions: A resident-performed LUS examination was a quicker imaging modality with superior sensitivity compared to clinician-interpreted CXR for PTX follow-up after tube thoracostomy in this Rwandan study. Lung ultrasound can be a valuable imaging tool for PTX follow-up, especially in resource-limited settings.
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http://dx.doi.org/10.1002/jum.15126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028462PMC
March 2020

Assessing rates and contextual predictors of 5-year mortality among HIV-infected and HIV-uninfected individuals following HIV testing in Durban, South Africa.

BMC Infect Dis 2019 Aug 28;19(1):751. Epub 2019 Aug 28.

Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA.

Background: Little is known about contextual factors that predict long-term mortality following HIV testing in resource-limited settings. We evaluated the impact of contextual factors on 5-year mortality among HIV-infected and HIV-uninfected individuals in Durban, South Africa.

Methods: We used data from the Sizanani trial (NCT01188941) in which adults (≥18y) were enrolled prior to HIV testing at 4 outpatient sites. We ascertained vital status via the South African National Population Register. We used random survival forests to identify the most influential predictors of time to death and incorporated these into a Cox model that included age, gender, HIV status, CD4 count, healthcare usage, health facility type, mental health, and self-identified barriers to care (i.e., service delivery, financial, logistical, structural and perceived health).

Results: Among 4816 participants, 39% were HIV-infected. Median age was 31y and 49% were female. 380 of 2508 with survival information (15%) died during median follow-up of 5.8y. For both HIV-infected and HIV-uninfected participants, each additional barrier domain increased the HR of dying by 11% (HR 1.11, 95% CI 1.05-1.18). Every 10-point increase in mental health score decreased the HR by 7% (HR 0.93, 95% CI 0.89-0.97). The hazard ratio (HR) for death of HIV-infected versus HIV-uninfected varied by age: HR of 6.59 (95% CI: 4.79-9.06) at age 20 dropping to a HR of 1.13 (95% CI: 0.86-1.48) at age 60.

Conclusions: Independent of serostatus, more self-identified barrier domains and poorer mental health increased mortality risk. Additionally, the impact of HIV on mortality was most pronounced in younger persons. These factors may be used to identify high-risk individuals requiring intensive follow up, regardless of serostatus.

Trial Registration: Clinical Trials.gov Identifier NCT01188941. Registered 26 August 2010.
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http://dx.doi.org/10.1186/s12879-019-4373-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712739PMC
August 2019

Reaching the second 90: the strategies for linkage to care and antiretroviral therapy initiation.

Curr Opin HIV AIDS 2019 11;14(6):494-502

Medical Practice Evaluation Center.

Purpose Of Review: We present recent literature describing interventions for linkage to HIV care in the era of Universal Test and Treat (UTT) policies. We also provide information for ongoing studies of linkage to care strategies registered with ClinicalTrials.gov.

Recent Findings: Differentiated service delivery for linkage to care involves implementing strategies that simplify and adapt HIV services to better serve individual needs and reduce unnecessary burdens on the health system. Recent strategies have focused not only on clinic-based populations testing for HIV but also emphasize community-based services and HIV self-testing, which create different challenges for linkage to the healthcare system. Some recent developments in linkage to care strategies include: case management, care integration with other desirable health services, financial incentives, home-based, and peer-led services. The demonstrated strategies have varying levels of success and engagement in care; further work is needed to address ongoing barriers in HIV care.

Summary: Progress towards meeting the 90-90-90 benchmarks has left gaps in linkage to care that require care-system development to facilitate increased access to care under UTT policies. Most notably, new strategies will need to focus on addressing the distinct needs of key populations and bolstering linkage to care from community-based and self-testing services.
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http://dx.doi.org/10.1097/COH.0000000000000579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798739PMC
November 2019
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