Declining HIV incidence in sub-Saharan Africa: a systematic review and meta-analysis of empiric data

Introduction: UNAIDS models suggest HIV incidence is declining in sub-Saharan Africa. The objective of this study was to assess whether modelled trends are supported by empirical evidence. Methods: We conducted a systematic review and meta-analysis of adult HIV incidence data from sub-Saharan Africa by searching Embase, Scopus, PubMed and OVID databases and technical reports published between 1 January 2010 and 23 July 2019. We included prospective and cross-sectional studies that directly measured incidence from blood samples. Incidence data were abstracted according to population risk group, geographic location, sex, intervention arm and calendar period. Weighted regression models were used to assess incidence trends across general population studies by sex. We also identified studies reporting greater than or equal to three incidence measurements since 2010 and assessed trends within them. Results: Total 291 studies, including 22 sub-Saharan African countries, met inclusion criteria. Most studies were conducted in South Africa (n = 102), Uganda (n = 46) and Kenya (n = 41); there were 26 countries with no published incidence data, most in western and central Africa. Data were most commonly derived from prospective observational studies (n = 163; 56%) and from geographically defined populations with limited demographic or risk-based enrolment criteria other than age (i.e., general population studies; n = 151; 52%). Across general population studies, average annual incidence declines since 2010 were 0.12/100 person-years (95% CI: 0.06–0.18; p = 0.001) among men and 0.10/100 person-years (95% CI: −0.02–0.22; p = 0.093) among women in eastern Africa, and 0.25/100 person-years (95% CI: 0.17–034; p < 0.0001) among men and 0.42/100 person-years (95% CI: 0.23–0.62; p = 0.0002) among women in southern Africa. In nine of 10 studies with multiple measurements, incidence declined over time, including in two studies of key populations. Across all population risk groups, the highest HIV incidence estimates were observed among men who have sex with men, with rates ranging from 1.0 to 15.4/100 person-years. Within general population studies, incidence was typically higher in women than men with a median female-to-male incidence rate ratio of 1.47 (IQR: 1.11 to 1.83) with evidence of a growing sex disparity over time. Conclusions: Empirical incidence data show the rate of new HIV infections is declining in eastern and southern Africa. However, recent incidence data are non-existent or very limited for many countries and key populations

Comparison of allocation strategies of convalescent plasma to reduce excess infections and mortality from SARS-CoV-2 in a US-like population

Background: While the use of convalescent plasma (CP) in the ongoing COVID-19 pandemic has been inconsistent, CP has the potential to reduce excess morbidity and mortality in future pandemics. Given constraints on CP supply, decisions surrounding the allocation of CP must be made. Study Design and Methods: Using a discrete-time stochastic compartmental model, we simulated implementation of four potential allocation strategies: administering CP to individuals in early hospitalization with COVID-19; administering CP to individuals in outpatient settings; administering CP to hospitalized individuals and administering any remaining CP to outpatient individuals and administering CP in both settings while prioritizing outpatient individuals. We examined the final size of SARS-CoV-2 infections, peak and cumulative hospitalizations, and cumulative deaths under each of the allocation scenarios over a 180-day period. We compared the cost per weighted health benefit under each strategy. Results: Prioritizing administration to patients in early hospitalization, with remaining plasma administered in outpatient settings, resulted in the highest reduction in mortality, averting on average 15% more COVID-19 deaths than administering to hospitalized individuals alone (95% CI [11%–18%]). Prioritizing administration to outpatients, with remaining plasma administered to hospitalized individuals, had the highest percentage of hospitalizations averted (22% [21%–23%] higher than administering to hospitalized individuals alone). Discussion: Convalescent plasma allocation strategy should be determined by the relative priority of averting deaths, infections, or hospitalizations. Under conditions considered, mixed allocation strategies (allocating CP to both outpatient and hospitalized individuals) resulted in a larger percentage of infections and deaths averted than administering CP in a single setting

The Role of Viral Introductions in Sustaining Community-Based HIV Epidemics in Rural Uganda: Evidence from Spatial Clustering, Phylogenetics, and Egocentric Transmission Models

Background:It is often assumed that local sexual networks play a dominant role in HIV spread in sub-Saharan Africa. The aim of this study was to determine the extent to which continued HIV transmission in rural communities-home to two-thirds of the African population-is driven by intra-community sexual networks versus viral introductions from outside of communities.Methods and Findings:We analyzed the spatial dynamics of HIV transmission in rural Rakai District, Uganda, using data from a cohort of 14,594 individuals within 46 communities. We applied spatial clustering statistics, viral phylogenetics, and probabilistic transmission models to quantify the relative contribution of viral introductions into communities versus community- and household-based transmission to HIV incidence. Individuals living in households with HIV-incident (n = 189) or HIV-prevalent (n = 1,597) persons were 3.2 (95% CI: 2.7-3.7) times more likely to be HIV infected themselves compared to the population in general, but spatial clustering outside of households was relatively weak and was confined to distances <500 m. Phylogenetic analyses of gag and env genes suggest that chains of transmission frequently cross community boundaries. A total of 95 phylogenetic clusters were identified, of which 44% (42/95) were two individuals sharing a household. Among the remaining clusters, 72% (38/53) crossed community boundaries. Using the locations of self-reported sexual partners, we estimate that 39% (95% CI: 34%-42%) of new viral transmissions occur within stable household partnerships, and that among those infected by extra-household sexual partners, 62% (95% CI: 55%-70%) are infected by sexual partners from outside their community. These results rely on the representativeness of the sample and the quality of self-reported partnership data and may not reflect HIV transmission patterns outside of Rakai.Conclusions:Our findings suggest that HIV introductions into communities are common and account for a significant proportion of new HIV infections acquired outside of households in rural Uganda, though the extent to which this is true elsewhere in Africa remains unknown. Our results also suggest that HIV prevention efforts should be implemented at spatial scales broader than the community and should target key populations likely responsible for introductions into communities.Please see later in the article for the Editors' Summary

Boosting of cross-reactive antibodies to endemic coronaviruses by SARS-CoV-2 infection but not vaccination with stabilized spike

Preexisting antibodies to endemic coronaviruses (CoV) that cross-react with SARS-CoV-2 have the potential to influence the antibody response to COVID-19 vaccination and infection for better or worse. In this observational study of mucosal and systemic humoral immunity in acutely infected, convalescent, and vaccinated subjects, we tested for cross-reactivity against endemic CoV spike (S) protein at subdomain resolution. Elevated responses, particularly to the β-CoV OC43, were observed in all natural infection cohorts tested and were correlated with the response to SARS-CoV-2. The kinetics of this response and isotypes involved suggest that infection boosts preexisting antibody lineages raised against prior endemic CoV exposure that cross-react. While further research is needed to discern whether this recalled response is desirable or detrimental, the boosted antibodies principally targeted the better-conserved S2 subdomain of the viral spike and were not associated with neutralization activity. In contrast, vaccination with a stabilized spike mRNA vaccine did not robustly boost cross-reactive antibodies, suggesting differing antigenicity and immunogenicity. In sum, this study provides evidence that antibodies targeting endemic CoV are robustly boosted in response to SARS-CoV-2 infection but not to vaccination with stabilized S, and that depending on conformation or other factors, the S2 subdomain of the spike protein triggers a rapidly recalled, IgG-dominated response that lacks neutralization activity.SCOPUS: ar.jinfo:eu-repo/semantics/publishe