Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 17 de 17
Filter
1.
Nat Microbiol ; 7(11): 1906-1917, 2022 11.
Article in English | MEDLINE | ID: covidwho-2087227

ABSTRACT

SARS-CoV-2 mutations that cause resistance to monoclonal antibody (mAb) therapy have been reported. However, it remains unclear whether in vivo emergence of SARS-CoV-2 resistance mutations alters viral replication dynamics or therapeutic efficacy in the immune-competent population. As part of the ACTIV-2/A5401 randomized clinical trial (NCT04518410), non-hospitalized participants with symptomatic SARS-CoV-2 infection were given bamlanivimab (700 mg or 7,000 mg) or placebo treatment. Here¸ we report that treatment-emergent resistance mutations [detected through targeted Spike (S) gene next-generation sequencing] were significantly more likely to be detected after bamlanivimab 700 mg treatment compared with the placebo group (7% of 111 vs 0% of 112 participants, P = 0.003). No treatment-emergent resistance mutations among the 48 participants who received 7,000 mg bamlanivimab were recorded. Participants in which emerging mAb resistant virus mutations were identified showed significantly higher pretreatment nasopharyngeal and anterior nasal viral loads. Daily respiratory tract viral sampling through study day 14 showed the dynamic nature of in vivo SARS-CoV-2 infection and indicated a rapid and sustained viral rebound after the emergence of resistance mutations. Participants with emerging bamlanivimab resistance often accumulated additional polymorphisms found in current variants of concern/interest that are associated with immune escape. These results highlight the potential for rapid emergence of resistance during mAb monotherapy treatment that results in prolonged high-level respiratory tract viral loads. Assessment of viral resistance should be prioritized during the development and clinical implementation of antiviral treatments for COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Mutation , Antibodies, Monoclonal
2.
Clin Infect Dis ; 2022 Oct 10.
Article in English | MEDLINE | ID: covidwho-2062886

ABSTRACT

Acute COVID-19 symptoms limit daily activities, but little is known about its association with SARS-CoV-2 viral burden. In this exploratory analysis of placebo recipients in the ACTIV-2/A5401 platform trial, we showed that high anterior nasal (AN) RNA levels and detectable plasma RNA were associated with delayed symptom improvement.

3.
Cell Rep Med ; 3(7): 100678, 2022 07 19.
Article in English | MEDLINE | ID: covidwho-2042205

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs) are among the treatments recommended for high-risk ambulatory persons with coronavirus 2019 (COVID-19). Here, we study viral culture dynamics post-treatment in a subset of participants receiving the mAb bamlanivimab in the ACTIV-2 trial (ClinicalTrials.gov: NCT04518410). Viral load by qPCR and viral culture are performed from anterior nasal swabs collected on study days 0 (day of treatment), 1, 2, 3, and 7. Treatment with mAbs results in rapid clearance of culturable virus. One day after treatment, 0 of 28 (0%) participants receiving mAbs and 16 of 39 (41%) receiving placebo still have culturable virus (p < 0.0001). Recrudescence of culturable virus is detected in three participants with emerging mAb resistance and viral RNA rebound. While further studies are necessary to fully define the relationship between shed culturable virus and transmission, these results raise the possibility that mAbs may offer immediate (household) and public-health benefits by reducing onward transmission.


Subject(s)
COVID-19 , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , COVID-19/drug therapy , Humans , SARS-CoV-2
4.
Nat Commun ; 13(1): 4931, 2022 08 22.
Article in English | MEDLINE | ID: covidwho-2000888

ABSTRACT

Anti-SARS-CoV-2 monoclonal antibodies are mainstay COVID-19 therapeutics. Safety, antiviral, and clinical efficacy of bamlanivimab were evaluated in the randomized controlled trial ACTIV-2/A5401. Non-hospitalized adults were randomized 1:1 within 10 days of COVID-19 symptoms to bamlanivimab or blinded-placebo in two dose-cohorts (7000 mg, n = 94; 700 mg, n = 223). No differences in bamlanivimab vs placebo were observed in the primary outcomes: proportion with undetectable nasopharyngeal SARS-CoV-2 RNA at days 3, 7, 14, 21, and 28 (risk ratio = 0.82-1.05 for 7000 mg [p(overall) = 0.88] and 0.81-1.21 for 700 mg [p(overall) = 0.49]), time to symptom improvement (median 21 vs 18.5 days [p = 0.97], 7000 mg; 24 vs 20.5 days [p = 0.08], 700 mg), or grade 3+ adverse events. However, bamlanivimab was associated with lower day 3 nasopharyngeal viral levels and faster reductions in inflammatory markers and viral decay by modeling. This study provides evidence of faster reductions in nasopharyngeal SARS-CoV-2 RNA levels but not shorter symptom durations in non-hospitalized adults with early variants of SARS-CoV-2.


Subject(s)
COVID-19 , Adult , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , Antibodies, Viral , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , RNA, Viral , SARS-CoV-2
5.
Clin Pharmacol Ther ; 112(6): 1207-1213, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1919261

ABSTRACT

AZD7442 (Evusheld) is a combination of two human anti-severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs), tixagevimab (AZD8895) and cilgavimab (AZD1061). Route of administration is an important consideration to improve treatment access. We assessed pharmacokinetics (PKs) of AZD7442 absorption following 600 mg administered intramuscularly (i.m.) in the thigh compared with 300 mg intravenously (i.v.) in ambulatory adults with symptomatic COVID-19. PK analysis included 84 of 110 participants randomized to receive i.m. AZD7442 and 16 of 61 randomized to receive i.v. AZD7442. Serum was collected prior to AZD7442 administration and at 24 hours and 3, 7, and 14 days later. PK parameters were calculated using noncompartmental methods. Following 600 mg i.m., the geometric mean maximum concentration (Cmax ) was 38.19 µg/mL (range: 17.30-60.80) and 37.33 µg/mL (range: 14.90-58.90) for tixagevimab and cilgavimab, respectively. Median observed time to maximum concentration (Tmax ) was 7.1 and 7.0 days for tixagevimab and cilgavimab, respectively. Serum concentrations after i.m. dosing were similar to the i.v. dose (27-29 µg/mL each component) at 3 days. The area under the concentration-time curve (AUC)0-7d geometric mean ratio was 0.9 for i.m. vs. i.v. Participants with higher weight or body mass index were more likely to have lower concentrations with either route. Women appeared to have higher interparticipant variability in concentrations compared with men. The concentrations of tixagevimab and cilgavimab after administration i.m. to the thigh were similar to those achieved with i.v. after 3 days from dosing. Exposure in the i.m. group was 90% of i.v. over 7 days. Administration to the thigh can be considered to provide consistent mAb exposure and improve access.


Subject(s)
COVID-19 , Humans , Adult , Male , Female , COVID-19/drug therapy , SARS-CoV-2 , Antibodies, Monoclonal
6.
J Acquir Immune Defic Syndr ; 90(4): 369-376, 2022 08 01.
Article in English | MEDLINE | ID: covidwho-1909060

ABSTRACT

BACKGROUND: Understanding the spectrum of COVID-19 in people with HIV (PWH) is critical to provide clinical guidance and risk reduction strategies. SETTING: Centers for AIDS Research Network of Integrated Clinic System, a US multisite clinical cohort of PWH in care. METHODS: We identified COVID-19 cases and severity (hospitalization, intensive care, and death) in a large, diverse HIV cohort during March 1, 2020-December 31, 2020. We determined predictors and relative risks of hospitalization among PWH with COVID-19, adjusted for disease risk scores. RESULTS: Of 16,056 PWH in care, 649 were diagnosed with COVID-19 between March and December 2020. Case fatality was 2%; 106 (16.3%) were hospitalized, and 12 died. PWH with current CD4 count <350 cells/mm 3 [aRR 2.68; 95% confidence interval (CI): 1.93 to 3.71; P < 0.001] or lowest recorded CD4 count <200 cells/mm 3 (aRR 1.67; 95% CI: 1.18 to 2.36; P < 0.005) had greater risks of hospitalization. HIV viral load and antiretroviral therapy status were not associated with hospitalization, although most of the PWH were suppressed (86%). Black PWH were 51% more likely to be hospitalized with COVID-19 compared with other racial/ethnic groups (aRR 1.51; 95% CI: 1.04 to 2.19; P = 0.03). Chronic kidney disease, chronic obstructive pulmonary disease, diabetes, hypertension, obesity, and increased cardiovascular and hepatic fibrosis risk scores were associated with higher hospitalization risk. PWH who were older, not on antiretroviral therapy, and with current CD4 count <350 cells/mm 3 , diabetes, and chronic kidney disease were overrepresented among PWH who required intubation or died. CONCLUSIONS: PWH with CD4 count <350 cells/mm 3 , and a history of CD4 count <200 cells/mm 3 , have a clear excess risk of severe COVID-19, accounting for comorbidities associated with severe outcomes. PWH with these risk factors should be prioritized for COVID-19 vaccination and early treatment and monitored closely for worsening illness.


Subject(s)
COVID-19 , HIV Infections , Renal Insufficiency, Chronic , CD4 Lymphocyte Count , COVID-19/complications , COVID-19/epidemiology , COVID-19 Vaccines , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Renal Insufficiency, Chronic/complications , United States/epidemiology
7.
AIDS ; 36(8): 1095-1103, 2022 07 01.
Article in English | MEDLINE | ID: covidwho-1909054

ABSTRACT

OBJECTIVES: To define the incidence of clinically detected coronavirus disease 2019 (COVID-19) in people with HIV (PWH) in the United States and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19. DESIGN: Observational study within the CFAR Network of Integrated Clinical Systems cohort in seven cities during 2020. METHODS: We calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4+ cell count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores. RESULTS: Among 16 056 PWH in care, of whom 44.5% were black, 12.5% were Hispanic, with a median age of 52 years (IQR 40-59), 18% had a current CD4+ cell count less than 350 cells/µl, including 7% less than 200; 95.5% were on antiretroviral therapy (ART), and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and black PWH respectively, than non-Hispanic white PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or black identity, lowest historical CD4+ cell count less than 350 cells/µl (proxy for CD4+ nadir), current low CD4+ : CD8+ ratio, diabetes, and obesity. CONCLUSION: Our results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWH. PWH with immune exhaustion as evidenced by lowest historical CD4+ cell count or current low CD4+ : CD8+ ratio had greater risk of COVID-19.


Subject(s)
COVID-19 , HIV Infections , Adult , COVID-19/epidemiology , COVID-19 Testing , Ethnicity , Female , HIV Infections/drug therapy , Humans , Incidence , Middle Aged , United States/epidemiology
8.
J Infect Dis ; 225(5): 856-861, 2022 03 02.
Article in English | MEDLINE | ID: covidwho-1666006

ABSTRACT

We tested the combination of a broadly neutralizing HIV antibody with the latency reversal agent vorinostat (VOR). Eight participants received 2 month-long cycles of VRC07-523LS with VOR. Low-level viremia, resting CD4+ T-cell-associated HIV RNA (rca-RNA) was measured, and intact proviral DNA assay (IPDA) and quantitative viral outgrowth assay (QVOA) were performed at baseline and posttreatment. In 3 participants, IPDA and QVOA declines were accompanied by significant declines of rca-RNA. However, no IPDA or QVOA declines clearly exceeded assay variance or natural decay. Increased resistance to VRC07-523LS was not observed. This combination therapy did not reduce viremia or the HIV reservoir. Clinical Trials Registration. NCT03803605.


Subject(s)
HIV Infections , HIV-1 , Broadly Neutralizing Antibodies , CD4-Positive T-Lymphocytes , HIV-1/genetics , Humans , Viremia/drug therapy , Virus Latency , Vorinostat/therapeutic use
9.
Clin Infect Dis ; 75(1): e1028-e1036, 2022 Aug 24.
Article in English | MEDLINE | ID: covidwho-1621585

ABSTRACT

BACKGROUND: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectious virus isolation in outpatients with coronavirus disease 2019 (COVID-19) has been associated with viral RNA levels and symptom duration, little is known about the host, disease, and viral determinants of infectious virus detection. METHODS: COVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay. RESULTS: Among 204 participants with mild-to-moderate symptomatic COVID-19, the median nasopharyngeal viral RNA was 6.5 (interquartile range [IQR] 4.7-7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (immunoglobulin (Ig)A, IgM, IgG, and/or total Ig) at baseline. Infectious virus was recovered in 7% of participants with SARS-CoV-2 antibodies compared to 58% of participants without antibodies (prevalence ratio [PR] = 0.12, 95% confidence interval [CI]: .04, .36; P = .00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; P < .0001) and fewer days since symptom onset (PR = 0.79, 95% CI: .71, .88 per day; P < .0001). CONCLUSIONS: The presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus. Seropositivity and viral RNA levels are likely more reliable markers of infectious virus clearance than subjective measure of COVID-19 symptom duration. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion. CLINICAL TRIALS REGISTRATION: NCT04405570.


Subject(s)
COVID-19 , Communicable Diseases , Adult , Antibodies, Viral , COVID-19 Testing , Humans , Immunoglobulin A , Outpatients , RNA, Viral , SARS-CoV-2
10.
Sci Transl Med ; 14(628): eabl7430, 2022 Jan 19.
Article in English | MEDLINE | ID: covidwho-1593318

ABSTRACT

There is an urgent need for an effective, oral, direct-acting therapeutic to block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent progression to severe coronavirus disease 2019 (COVID-19). In a phase 2a double-blind, placebo-controlled, randomized, multicenter clinical trial, we evaluated the safety, tolerability, and antiviral efficacy of the nucleoside analog molnupiravir in 202 unvaccinated participants with confirmed SARS-CoV-2 infection and symptom duration <7 days. Participants were randomized 1:1 to receive molnupiravir (200 mg) or placebo and then 3:1 to receive molnupiravir (400 or 800 mg) or placebo, orally twice daily for 5 days. Antiviral activity was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 RNA in nasopharyngeal swabs. Infectious virus was assessed by inoculation of cultured Vero cells with samples from nasopharyngeal swabs and was detected by RT-PCR. Time to viral RNA clearance (primary endpoint) was decreased in the 800-mg molnupiravir group (median 14 days) compared to the placebo group (median 15 days) (log rank P value = 0.013). Of participants receiving 800 mg of molnupiravir, 92.5% achieved viral RNA clearance compared with 80.3% of placebo recipients by study end (4 weeks). Infectious virus (secondary endpoint) was detected in swabs from 1.9% of the 800-mg molnupiravir group compared with 16.7% of the placebo group at day 3 of treatment (P = 0.016). At day 5 of treatment, infectious virus was not isolated from any participants receiving 400 or 800 mg of molnupiravir compared with 11.1% of placebo recipients (P = 0.034 and 0.027, respectively). Molnupiravir was well tolerated across all doses.


Subject(s)
COVID-19 , Animals , Chlorocebus aethiops , Cytidine/analogs & derivatives , Humans , Hydroxylamines , RNA, Viral/genetics , SARS-CoV-2 , Treatment Outcome , Vero Cells
12.
Open forum infectious diseases ; 8(Suppl 1):S807-S808, 2021.
Article in English | EuropePMC | ID: covidwho-1564094

ABSTRACT

Background SARS-CoV-2 continues to spread and the development of safe and effective therapeutics for the prevention of severe disease remains a priority. BRII-196 and BRII-198 are non-competing anti-SARS-CoV-2 mAbs with YTE triple amino acid substitution in Fc to extend half-life and reduce receptor binding, that are being studied for treatment of COVID-19 in the ACTIV-2 Trial, sponsored by NIAID and led by ACTG. Methods ACTIV-2 evaluates safety/efficacy of investigational agents for treatment of non-hospitalized adults with mild-moderate COVID-19 under a randomized, blinded, controlled adaptive platform. BRII-196/BRII-198 (1000 mg each) as a single dose given as sequential infusions, or placebo to those at high risk of clinical progression (i.e., age ≥ 60 years or presence of other medical conditions) within 10 days of symptom onset and positive test for SARS-CoV-2. The primary endpoint was hospitalization and/or death through day 28. We report Phase 3 BRII-196/BRII-198 trial results per DSMB recommendation following an interim analysis. Results Between January and July 2021, 837 participants (418 active, 419 placebo) from sites in the US (66%), Brazil, South Africa, Mexico, Argentina and the Philippines were randomized and received study product at time of emerging variants. Median age 49 years (Q1, Q3: 39, 58), 51% female, 17% Black/African-American and 49% Hispanic/Latino, with median 6 days from symptom onset. At interim analysis 71% and 97% had a day 28 and 7 visit, respectively. For all available data at interim review, BRII-196/BRII-198 compared to placebo had fewer hospitalizations (12 vs. 45) and deaths (1 vs. 9). At day 28 of follow-up, there was an estimated 78% reduction in hospitalization and/or death (2.4 vs. 11.1%), relative risk 0.22 (95% CI: 0.05, 0.86), P=0.00001 (nominal one-sided). Grade 3 or higher adverse events (AEs) were observed less frequently among BRII-196/BRII-198 participants than placebo (3.8% vs. 13.4%) with no severe infusion reactions or drug related serious AEs. Conclusion BRII-196/BRII-198 was safe, well-tolerated, and demonstrated significant reduction compared to placebo in the risk of hospitalization and/or death among adults with mild-moderate COVID-19 at high risk for progression to severe disease. Disclosures Kara W. Chew, MD, MS, Amgen (Individual(s) Involved: Self): Grant/Research Support;Merck Sharp & Dohme (Individual(s) Involved: Self): Grant/Research Support David Alain Wohl, MD, Gilead Sciences (Individual(s) Involved: Self): Advisor or Review Panel member, Consultant, Research Grant or Support, Scientific Research Study Investigator;Janssen (Individual(s) Involved: Self): Advisor or Review Panel member;Merck (Individual(s) Involved: Self): Advisor or Review Panel member, Research Grant or Support;ViiV (Individual(s) Involved: Self): Advisor or Review Panel member, Research Grant or Support Joseph J. Eron, MD, Gilead Sciences (Consultant, Research Grant or Support)Janssen (Consultant, Research Grant or Support)Merck (Consultant)ViiV (Consultant, Research Grant or Support) David A. Margolis, MD MPH, Brii Biosciences (Employee) Courtney Fletcher, Pharm.D., National Institute of Allergy and Infectious Diseases, NIH (Grant/Research Support) Davey Smith, M.D., Linear Therapies, Matrix Biomed, Bayer (Consultant, Shareholder) Eric Daar, Gilead (Consultant, Grant/Research Support)Merck (Consultant)ViiV (Consultant, Grant/Research Support)

13.
Clin Infect Dis ; 73(9): 1717-1721, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501059

ABSTRACT

As of March 2021, coronavirus disease 2019 (COVID-19) had caused more than 123 million infections and almost 3 million deaths worldwide. Dramatic advances have been made in vaccine development and nonpharmaceutical interventions to stop the spread of infection. However, treatments to stop disease progression are limited. A wide variety of "repurposed" drugs evaluated for treatment of COVID-19 have had little or no benefit. More recently, intravenous monoclonal antibody (mAb) combinations have been authorized by the US Food and Drug Administration for emergency use for outpatients with mild to moderate COVID-19 including some active against emerging severe acute respiratory syndrome coronavirus 2 variants of concern. Easier to administer therapeutics including intramuscular and subcutaneous mAbs and oral antivirals are in clinical trials. Reliable, safe, effective COVID-19 treatment for early infection in the outpatient setting is of urgent and critical importance. Availability of such treatment should lead to reduced progression of COVID-19.


Subject(s)
COVID-19 , Pharmaceutical Preparations , COVID-19/drug therapy , Humans , Outpatients , SARS-CoV-2
14.
Healthc (Amst) ; 9(4): 100581, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1401487

ABSTRACT

The interleukin-6 receptor antagonist tocilizumab became widely used early in the coronavirus disease 2019 (COVID-19) pandemic based on small observational studies that suggested clinical benefit in COVID-19 patients with a hyperinflammatory state. To inform our local treatment algorithms in the absence of randomized clinical trial results, we performed a rapid analysis of the first 11 hospitalized COVID-19 patients treated with tocilizumab at our academic medical center. We report their early clinical outcomes and describe the process by which we assembled a team of diverse trainees and stakeholders to extract, analyze, and disseminate data during a time of clinical uncertainty.


Subject(s)
COVID-19 , Antibodies, Monoclonal, Humanized , COVID-19/drug therapy , Clinical Decision-Making , Cytokine Release Syndrome , Humans , Off-Label Use , Pandemics , SARS-CoV-2 , Treatment Outcome , Uncertainty
15.
EClinicalMedicine ; 37: 100968, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1290307

ABSTRACT

BACKGROUND: We evaluated features of HIV transmission networks involving persons diagnosed during incident HIV infection (IHI) to assess network-based opportunities to curtail onward transmission. METHODS: Transmission networks were constructed using partial pol sequences reported to North Carolina surveillance among persons with recent (2014-2018) and past (<2014) HIV diagnoses. IHI were defined as documented acute infections or seroconversion. Demographic and virologic features of HIV genetic clusters (<1.5% pairwise genetic distance) involving ≥ 1 IHI were assessed. Persons with viral genetic links and who had diagnoses >90 days prior to an IHI were further characterized. We assessed named partner outcomes among IHI index persons using contact tracing data. FINDINGS: Of 4,405 HIV diagnoses 2014-2018 with sequences, there were 323 (7%) IHI index persons; most were male (88%), Black (65%), young (68% <30 years), and reported sex with men (MSM) risk (79%). Index persons were more likely to be cluster members compared to non-index persons diagnosed during the same period (72% vs. 49%). In total, 162 clusters were identified involving 233 IHI, 577 recent diagnoses, and 163 past diagnoses. Most IHI cases (53%) had viral linkages to ≥1 previously diagnosed person without evidence of HIV viral suppression in the year prior to the diagnosis of the IHI index. In contact tracing, only 53% IHI cases named an HIV-positive contact, resulting in 0.5 previously diagnosed persons detected per IHI investigated. When combined with viral analyses, the detection rate of viremic previously diagnosed persons increased to 1.3. INTERPRETATION: Integrating public health with molecular epidemiology, revealed that more than half of IHI have viral links to persons with previously diagnosed unsuppressed HIV infection which was largely unrecognized by traditional contact tracing. Enhanced partner services to support engagement and retention in HIV care and improved case finding supported by rapid phylogenetic analysis are tools to substantially reduce onward HIV transmission.

16.
Clin Infect Dis ; 72(6): 1093-1100, 2021 03 15.
Article in English | MEDLINE | ID: covidwho-1132462

ABSTRACT

There is a proliferation of clinical trials worldwide to find effective therapies for patients diagnosed with coronavirus disease 2019 (COVID-19). The endpoints that are currently used to evaluate the efficacy of therapeutic agents against COVID-19 are focused on clinical status at a particular day or on time to a specific change of clinical status. To provide a full picture of the clinical course of a patient and make complete use of available data, we consider the trajectory of clinical status over the entire follow-up period. We also show how to combine the evidence of treatment effects on the occurrences of various clinical events. We compare the proposed and existing endpoints through extensive simulation studies. Finally, we provide guidelines on establishing the benefits of treatments.


Subject(s)
COVID-19 , Clinical Trials as Topic , Humans , SARS-CoV-2
17.
JAMA ; 324(16): 1651-1669, 2020 10 27.
Article in English | MEDLINE | ID: covidwho-865967

ABSTRACT

Importance: Data on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices. Objective: To evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV. Evidence Review: New evidence was collected since the previous International Antiviral (formerly AIDS) Society-USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations. Findings: From 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic. Conclusion and Relevance: Advances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.


Subject(s)
Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/prevention & control , AIDS-Related Opportunistic Infections/drug therapy , Age Factors , Anti-Retroviral Agents/economics , Betacoronavirus , COVID-19 , Comorbidity , Coronavirus Infections/epidemiology , Drug Administration Schedule , Drug Costs , Drug Resistance, Viral/genetics , Drug Substitution/standards , Drug Therapy, Combination/methods , Female , HIV Infections/blood , HIV Infections/diagnosis , Humans , International Agencies , Male , Pandemics , Pneumonia, Viral/epidemiology , Polypharmacy , Pre-Exposure Prophylaxis/methods , Pregnancy , Pregnancy Complications, Infectious/drug therapy , RNA, Viral/blood , SARS-CoV-2 , Societies, Medical , United States , Viral Load/genetics
SELECTION OF CITATIONS
SEARCH DETAIL