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To assess the prevalence of persistent functional impairment after COVID-19, we assessed 118 individuals 3-4 months after their initial COVID-19 diagnosis with a symptom survey, work productivity and activity index questionnaire, and 6-minute walk test. We found significant persistent symptoms and functional impairment, even in non-hospitalized patients with COVID-19.

We investigated feasibility and accuracy of an interferon-gamma release assay (IGRA) for detection of T cell responses to SARS-CoV-2. Whole blood IGRA accurately distinguished between convalescents and uninfected healthy blood donors with a predominantly CD4+ T cell response. SARS-CoV-2 IGRA may serve as a useful diagnostic tool in managing the COVID-19 pandemic.

Despite the recent rollout of Isoniazid Preventive Therapy (IPT) to prevent TB in people living with HIV in South Africa, adherence and completion rates are low. To explore barriers to IPT completion in rural KwaZulu-Natal, South Africa, we conducted individual semi-structured interviews among 30 HIV patients who had completed or defaulted IPT. Interview transcripts were analyzed according to the framework method of qualitative analysis. Facilitators of IPT completion included knowledge of TB and IPT, accepting one’s HIV diagnosis, viewing IPT as similar to antiretroviral therapy, having social support in the community and the clinic, trust in the healthcare system, and desire for health preservation. Barriers included misunderstanding of IPT’s preventive role in the absence of symptoms, inefficient health service delivery, ineffective communication with healthcare workers, financial burden of transport to clinic and lost wages, and competing priorities. HIV-related stigma was not identified as a significant barrier to IPT completion, and participants felt confident in their ability to manage stigma, for example by pretending their medications were for unrelated conditions. Completers were more comfortable communicating with health care workers than were defaulters. Efforts to facilitate successful IPT completion must include appropriate counseling and education for individual patients and addressing inefficiencies within the health care system in order to minimize patients’ financial and logistical burden. These patient-level and structural changes are necessary for IPT to successfully reduce TB incidence in this resource-limited setting.

Type III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized, single-blind, placebo-controlled trial (NCT04331899) in 120 outpatients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) within 72 hours of diagnosis could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively, and symptom duration did not differ significantly between groups (HR 0.94; 95% CI 0.64 to 1.39). Both Lambda and placebo were well-tolerated, though liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.

Type III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized placebo-controlled trial in 120 patients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint, NCT04331899). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively (HR 0.94; 95% CI 0.64 to 1.39). At enrollment; 41% of subjects were SARS-CoV-2 IgG seropositive; compared to placebo, lambda tended to delay shedding cessation in seronegatives (aHR 0.66, 95% CI 0.39-1.10) and to hasten shedding cessation in seropositives (aHR 1.58, 95% CI 0.88-2.86; p for interaction = 0.03). Liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.

BackgroundHIV and tuberculosis (TB) coinfection remains a major public health threat in sub-Saharan Africa. Integration and decentralization of HIV and TB treatment services are being implemented, but data on outcomes of this strategy are lacking in rural, resource-limited settings. We evaluated TB treatment outcomes in TB/HIV coinfected patients in an integrated and decentralized system in rural KwaZulu-Natal, South Africa.MethodsWe retrospectively studied a cohort of HIV/TB coinfected patients initiating treatment for drug-susceptible TB at a district hospital HIV clinic from January 2012-June 2013. Patients were eligible for down-referral to primary health clinics(PHCs) for TB treatment completion if they met specific clinical criteria. Records were reviewed for patients’ demographic, baseline clinical and laboratory information, past HIV and TB history, and TB treatment outcomes.ResultsOf 657(88.7%) patients, 322(49.0%) were female, 558(84.9%) were new TB cases, and 572(87.1%) had pulmonary TB. After TB treatment initiation, 280(42.6%) were down-referred from the district level HIV clinic to PHCs for treatment completion; 377(57.4%) remained at the district hospital. Retained patients possessed characteristics indicative of more severe disease. In total, 540(82.2%) patients experienced treatment success, 69(10.5%) died, and 46(7.0%) defaulted. Down-referred patients experienced higher treatment success, and lower mortality, but were more likely to default, primarily at the time of transfer to PHC.ConclusionDecentralization of TB treatment to the primary care level is feasible in rural South Africa. Treatment outcomes are favorable when patients are carefully chosen for down-referral. Higher mortality in retained patients reflects increased baseline disease severity while higher default among down-referred patients reflects failed linkage of care. Better linkage mechanisms are needed including improved identification of potential defaulters, increased patient education, active communication between hospitals and PHCs, and tracing of patients lost to follow up. Decentralized and integrated care is successful for carefully selected TB/HIV coinfected patients and should be expanded.

The integrase strand transfer inhibitor (INSTI) class of antiretroviral therapy (ART) may result in faster time to virologic suppression compared with regimens that contain protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, differences in time to achieve virologic suppression are not well-defined in routine clinical settings with contemporary antiretroviral agents.Study was a retrospective single-center study of treatment-naïve human immunodeficiency virus (HIV) patients initiating ART between 2013 and 2016. Among patients on different ART regimen types, we compared rates of and median time to virologic suppression [viral load (VL) <50 copies/mL].A total of 155 patients—45 (29%) female and 110 (71%) male—met study inclusion criteria. Median age was 42 years (interquartile range 31–52), and median baseline CD4 count was 288 cells/μL and VL was 60,000 copies/mL. Seventy-one (46%) initiated an INSTI-based regimen, 58 (37%) were on NNRTI-based regimens, and 26 (17%) on PI-based regimens. In total, 112 (72%) patients achieved virologic suppression at 12 months. Patients on INSTI-based regimens were more likely to achieve virologic suppression by 3, 6, and 12 months (P < .01), and had lower median time to suppression (60 vs 137 days on NNRTI-based regimens and 147 days on PI-based regimens, P < .01).Patients on INSTI-based ART regimens in a real-world setting experienced higher rates of virologic suppression and shorter time from ART initiation to virologic suppression. For HIV patients on INSTI-based ART regimens, virologic failure should be suspected in those with VLs >50 copies/mL before the current recommendation of 48 weeks.