A Prospective Study of Key Correlates for Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2

Background: Randomized controlled trials evaluated monoclonal antibodies for the treatment (Study 2067) and prevention (Study 2069) of coronavirus disease 2019 (COVID-19). Household contacts of the infected index case in Study 2067 were enrolled in Study 2069 and prospectively followed; these cohorts provided a unique opportunity to evaluate correlates of transmission, specifically viral load. Methods: This post hoc analysis was designed to identify and evaluate correlates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, adjusting for potential confounding factors related to source SARS-CoV-2 viral load and risk of SARS-CoV-2 acquisition in this population. Correlates of transmission were evaluated in potential transmission pairs (any infected household member plus susceptible household contact). Results: In total, 943 participants were included. In multivariable regression, 2 potential correlates were determined to have a statistically significant (P <. 05) association with transmission risk. A 10-fold increase in viral load was associated with a 40% increase in odds of transmission; sharing a bedroom with the index participant was associated with a 199% increase in odds of transmission. Conclusions: In this prospective, post hoc analysis that controlled for confounders, the 2 key correlates for transmission of SARS-CoV-2 within a household are sharing a bedroom and increased viral load, consistent with increased exposure to the infected individual

Assessing the Combined Public Health Impact of Pharmaceutical Interventions on Pandemic Transmission and Mortality: An Example in SARS CoV-2

To assess the combined role of anti-viral monoclonal antibodies (mAbs) and vaccines in reducing severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission and mortality in the United States, an agent-based model was developed that accounted for social contacts, movement/travel, disease progression, and viral shedding. The model was calibrated to coronavirus disease 2019 (COVID-19) mortality between October 2020 and April 2021 (aggressive pandemic phase), and projected an extended outlook to estimate mortality during a less aggressive phase (April–August 2021). Simulated scenarios evaluated mAbs for averting infections and deaths in addition to vaccines and aggregated non-pharmaceutical interventions. Scenarios included mAbs as a treatment of COVID-19 and for passive immunity for postexposure prophylaxis (PEP) during a period when variants were susceptible to the mAbs. Rapid diagnostic testing paired with mAbs was evaluated as an early treatment-as-prevention strategy. Sensitivity analyses included increasing mAb supply and vaccine rollout. Allocation of mAbs for use only as PEP averted up to 14% more infections than vaccine alone, and targeting individuals ≥ 65 years averted up to 37% more deaths. Rapid testing for earlier diagnosis and mAb use amplified these benefits. Doubling the mAb supply further reduced infections and mortality. mAbs provided benefits even as proportion of the immunized population increased. Model projections estimated that ~ 42% of expected deaths between April and August 2021 could be averted. Assuming sensitivity to mAbs, their use as early treatment and PEP in addition to vaccines would substantially reduce SARS-CoV-2 transmission and mortality even as vaccination increases and mortality decreases. These results provide a template for informing public health policy for future pandemic preparedness

Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19

BACKGROUND REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous REGEN-COV prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent Covid-19 in persons at high risk for infection because of household exposure to a person with SARS-CoV-2 infection is unknown. METHODS We randomly assigned, in a 1:1 ratio, participants (=12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARSCoV- 2 infection to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection. At the time of randomization, participants were stratified according to the results of the local diagnostic assay for SARS-CoV-2 and according to age. The primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28 in participants who did not have SARS-CoV-2 infection (as measured by reverse-transcriptase- quantitative polymerase-chain-reaction assay) or previous immunity (seronegativity). RESULTS Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P104 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted. CONCLUSIONS Subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load

Diagnosis and promotion of serostatus awareness in sub-Saharan Africa

Summary: Evaluation of novel and cost-effective strategies to increase HIV testing and linkage to care among women, men and couples is a key priority for sub-Saharan Africa, to link HIV positive individuals to care, including antiretroviral therapy (ART) for clinical and prevention benefits, and HIV-negative individuals to prevention strategies. To date, HIV counseling and testing (HCT) uptake through facility-based HCT has been low, with logistic, convenience and confidentiality concerns reported as barriers. Mobile and home-based HCT strategies address these barriers and achieve high population-level coverage of HCT and linkage to care and reach target groups such as men who are not otherwise tested. To achieve wide-spread knowledge of HIV serostatus, which is the corner-stone for evidence based HIV prevention, a combination of HCT strategies is likely necessary to engage women, men, couples and young people in HIV care and prevention.

Empowering patients to link to care and treatment: qualitative findings about the role of a home-based HIV counselling, testing and linkage intervention in South Africa

To explore the barriers and facilitators of linkage to and retention in care amongst persons who tested positive for HIV, qualitative research was conducted in a home-based HIV counselling and testing (HBCT) project with interventions to facilitate linkages to HIV care in rural KwaZulu-Natal, South Africa. The intervention tested 1272 adults for HIV in Vulindlela of whom 32% were HIV positive, received point-of-care (POC) CD4 testing and referral to local HIV clinics. Those testing positive also received follow-up visits from a counsellor to evaluate linkages to care. The study employed a qualitative methodology collecting data through in-depth semi-structured interviews. Respondents included 25 HI positive persons who had tested as part of HBCT project, 4 intervention research counsellors who delivered the HBCT intervention and 9 government clinic staff who received referrals for care. The results show that HBCT helped to facilitate linkage to care through providing education and support to help overcome fears of stigma and discrimination. The results show the perceived value of receiving a POC CD4 result during post-test counselling, both for those newly diagnosed and those previously diagnosed as HIV positive. The results also demonstrate that in-depth counselling creates an educated consumer facilitating engagement with clinical services. The study provides qualitative insights into the acceptability of confidential HBCT with same day POC CD4 testing and counselling as factors that influenced HIV-positive persons' decisions to link to care. This model warrants further evaluation in non-research settings to determine impact and cost-effectiveness relative to other HIV testing and referral strategies.

Cost-effectiveness of community-based strategies to strenghthen the continuum of HIV care in rural South Africa: a health economic modelling analysis

Home HIV counselling and testing (HTC) achieves high coverage of testing and linkage to care compared with existing facility-based approaches, particularly among asymptomatic individuals. In a modelling analysis the authors aimed to assess the effect on population-level health and cost-effectiveness of a community-based package of home HTC in KwaZulu-Natal, South Africa.

Home testing and counselling to reduce HIV incidence in a generalised epidemic setting: a mathematical modelling analysis

Home HIV testing and counselling (HTC) achieves high levels of HIV testing and linkage to care. Periodic home HTC, particularly targeted to those with high HIV viral load, might facilitate expansion of antiretroviral therapy (ART) coverage. We used a mathematical model to assess the eff ect of periodic home HTC programmes on HIV incidence in KwaZulu-Natal, South Africa.

High HIV testing uptake and linkage to care in a novel program of home-based HIV counseling and testing with facilitated referral in KwaZulu-Natal, South Africa

For antiretroviral therapy (ART) to have a population level HIV prevention impact, high levels of HIV testing and effective linkages to HIV care among HIV-infected persons are required. Methods: We piloted home-based counseling and testing (HBCT) with point-of-care CD4 count testing and follow-up visits to facilitate linkage of HIV-infected persons to local HIV clinics and uptake of ART in rural KwaZulu-Natal, South Africa. Lay counselor follow-up visits at months one, three and six evaluated the primary outcome of linkage to care. Plasma viral load was measured at baseline and month six. 671 adults were tested for HIV (91% coverage) and 201 (30%) were HIV-infected, of which 73 (36%) were new diagnoses. By month three, 90% of HIV-infected persons not on ART at baseline had visited an HIV clinic and 80% of those eligible for ART at baseline by South African guidelines (CD4?200 cells/mL at the time of the study) had initiated ART. Among HIV-infected participants who were eligible for ART at baseline, mean viral load decreased by 3.23 log10 copies/mL (p<0.001) and the proportion with viral load suppression increased from 20% to 80% between baseline and month six. In this pilot of HBCT and linkages to care in KwaZulu-Natal, 91% of adults were tested for HIV. Linkage to care was ;90% both among newly-identified HIV-infected persons as well as known HIVinfected persons who were not engaged in care.

Initiation of antiretroviral therapy and viral suppression after home HIV testing and counselling in KwaZulu-Natal, South Africa, and Mabarara district, Uganda: a prospective, observational intervention study

Antiretroviral therapy significantly decreases HIV-associated morbidity, mortality, and HIV transmission through HIV viral load suppression. In settings of high prevalence, outreach strategies are needed to find asymptomatic HIV-positive people, to link them to HIV care, to initiate antiretroviral therapy, and to achieve viral suppression. We aimed to assess the effect of a community-based strategy of HIV testing and counselling (HTC) and linkage to care in households. We did an uncontrolled prospective intervention study in 1600 households in two rural communities in KwaZulu-Natal, South Africa, and Mbabara district, Uganda, between Sept 27, 2011, and May 6, 2013. The intervention consisted of home HTC and, for HIV-positive people, point-of-care CD4 count testing, referral to care, and follow-up visits by lay counsellors, including the off er of couples HTC. We identifi ed 3545 adults in 1549 households in the two communities. 3393 adults (96%) were enrolled and tested for HIV, of whom 635 (19%) were HIV positive. At baseline, 229 (36%) HIV-positive people were newly identifi ed, 406 (64%) were previously known to be HIV positive, and 254 (40%) were taking antiretroviral therapy. By month 12, 619 (97%) HIV-positive people had visited an HIV clinic, and of 123 participants eligible for antiretroviral therapy, 94 (76%) had initiated antiretroviral therapy by 12 months. Of the 77 participants on antiretroviral therapy by month 9, 59 (77%) achieved viral suppression by month 12. Among all HIV-positive people, the number with viral suppression (<1000 copies per mL) increased from 287 (50%) to 370 (65%; p<0.0001) at 12 months. There were no reported cases of study-related social harm during the study. Community-based HTC in rural South Africa and Uganda achieved high coverage of testing and linkage to care. Among people eligible for antiretroviral therapy, a high proportion initiated antiretroviral therapy and achieved viral suppression, suggesting high adherence. Our results could be generalisable to other southern African countries with a high burden of HIV, but pilot studies would be useful in other settings before initiation of clinical trials to estimate the effectiveness and cost-effectiveness of the intervention.

Associations between schistosomiasis and HIV-1 acquisition risk in four prospective cohorts: a nested case-control analysis

Introduction Globally, schistosomes infect approximately 200 million people, with 90% of infections in sub-Saharan Africa. Schistosomiasis is hypothesized to increase HIV-1 acquisition risk, and multiple cross-sectional studies reported strong associations. We evaluated this hypothesis within four large prospective cohorts. Methods We conducted nested case-control analyses within three longitudinal cohorts of heterosexual HIV-1 serodiscordant couples and one female sex worker (FSW) cohort from Kenya and Uganda. The serodiscordant couples studies were conducted between 2004 and 2012 while the FSW cohort analysis included participant follow-up from 1993 to 2014. Cases HIV-1 seroconverted during prospective follow-up; three controls were selected per case. The presence of circulating anodic antigen in archived serum, collected prior to HIV-1 seroconversion, identified participants with active schistosomiasis; immunoblots determined the schistosome species. Data from serodiscordant couples cohorts were pooled, while the FSW cohort was analysed separately to permit appropriate confounder adjustment. Results We included 245 HIV-1 seroconverters and 713 controls from the serodiscordant couples cohorts and 330 HIV-1 seroconverters and 962 controls from the FSW cohort. The prevalence of active schistosomiasis was 20% among serodiscordant couples and 22% among FSWs. We found no association between schistosomiasis and HIV-1 acquisition risk among males (adjusted odds ratio (aOR) = 0.99, 95% CI 0.59 to 1.67) or females (aOR = 1.21, 95% CI 0.64 to 2.30) in serodiscordant couples. Similarly, in the FSW cohort we detected no association (adjusted incidence rate ratio (aIRR) = 1.11, 95% CI 0.83 to 1.50). Exploring schistosome species-specific effects, there was no statistically significant association between HIV-1 acquisition risk andSchistosoma mansoni(serodiscordant couples: aOR = 0.90, 95% CI 0.56 to 1.44; FSW: aIRR = 0.83, 95% CI 0.53 to 1.20) orSchistosoma haematobium(serodiscordant couples: aOR = 1.06, 95% CI 0.46 to 2.40; FSW: aIRR = 1.64, 95% CI 0.93 to 2.87) infection. Conclusions Schistosomiasis was not a strong risk factor for HIV-1 acquisition in these four prospective studies.S. mansoniwas responsible for the majority of schistosomiasis in these cohorts, and our results do not support the hypothesis thatS. mansoniinfection is associated with increased HIV-1 acquisition risk.S. haematobiuminfection was associated with a point estimate of elevated HIV-1 risk in the FSW cohort that was not statistically significant, and there was no trend towards a positive association in the serodiscordant couples cohorts.Host-parasite interactio