The Relationship Between the Human Immunodeficiency Virus-1 Transmission Network and the HIV Care Continuum in Los Angeles County.

BACKGROUND: Public health action combating human immunodeficiency virus (HIV) includes facilitating navigation through the HIV continuum of care: timely diagnosis followed by linkage to care and initiation of antiretroviral therapy to suppress viral replication. Molecular epidemiology can identify rapidly growing HIV genetic transmission clusters. How progression through the care continuum relates to transmission clusters has not been previously characterized. METHODS: We performed a retrospective study on HIV surveillance data from 5226 adult cases in Los Angeles County diagnosed from 2010 through 2014. Genetic transmission clusters were constructed using HIV-TRACE. Cox proportional hazard models were used to estimate the impact of transmission cluster growth on the time intervals between care continuum events. Gamma frailty models incorporated the effect of heterogeneity associated with genetic transmission clusters. RESULTS: In contrast to our expectations, there were no differences in time to the care continuum events among individuals in clusters with different growth dynamics. However, upon achieving viral suppression, individuals in high growth clusters were slower to experience viral rebound (hazard ratio 0.83, P = .011) compared with individuals in low growth clusters. Heterogeneity associated with cluster membership in the timing to each event in the care continuum was highly significant (P < .001), with and without adjustment for transmission risk and demographics. CONCLUSIONS: Individuals within the same transmission cluster have more similar trajectories through the HIV care continuum than those across transmission clusters. These findings suggest molecular epidemiology can assist public health officials in identifying clusters of individuals who may benefit from assistance in navigating the HIV care continuum.

Interplay Between Geography and HIV Transmission Clusters in Los Angeles County.

BACKGROUND: Clusters of HIV diagnoses in time and space and clusters of genetically linked cases can both serve as alerts for directing prevention and treatment activities. We assessed the interplay between geography and transmission across the Los Angeles County (LAC) HIV genetic transmission network. METHODS: Deidentified surveillance data reported for 8186 people with HIV residing in LAC from 2010 through 2016 were used to construct a transmission network using HIV-TRACE. We explored geographic assortativity, the tendency for people to link within the same geographic region; concordant time-space pairs, the proportion of genetically linked pairs from the same geographic region and diagnosis year; and Jaccard coefficient, the overlap between geographical and genetic clusters. RESULTS: Geography was assortative in the genetic transmission network but less so than either race/ethnicity or transmission risk. Only 18% of individuals were diagnosed in the same year and location as a genetically linked partner. Jaccard analysis revealed that cis-men and younger age at diagnosis had more overlap between genetic clusters and geography; the inverse association was observed for trans-women and Blacks/African Americans. CONCLUSIONS: Within an urban setting with endemic HIV, genetic clustering may serve as a better indicator than time-space clustering to understand HIV transmission patterns and guide public health action.

Sorting by Race/Ethnicity Across HIV Genetic Transmission Networks in Three Major Metropolitan Areas in the United States.

An important component underlying the disparity in HIV risk between race/ethnic groups is the preferential transmission between individuals in the same group. We sought to quantify transmission between different race/ethnicity groups and measure racial assortativity in HIV transmission networks in major metropolitan areas in the United States. We reconstructed HIV molecular transmission networks from viral sequences collected as part of HIV surveillance in New York City, Los Angeles County, and Cook County, Illinois. We calculated assortativity (the tendency for individuals to link to others with similar characteristics) across the network for three candidate characteristics: transmission risk, age at diagnosis, and race/ethnicity. We then compared assortativity between race/ethnicity groups. Finally, for each race/ethnicity pair, we performed network permutations to test whether the number of links observed differed from that expected if individuals were sorting at random. Transmission networks in all three jurisdictions were more assortative by race/ethnicity than by transmission risk or age at diagnosis. Despite the different race/ethnicity proportions in each metropolitan area and lower proportions of clustering among African Americans than other race/ethnicities, African Americans were the group most likely to have transmission partners of the same race/ethnicity. This high level of assortativity should be considered in the design of HIV intervention and prevention strategies.

Prognosis of COVID-19 in patients with breast cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a pandemic in the world and posed a great threat to people's health. Several meta-analyses have indicated that many comorbidities were associated with increased risk of COVID-19 severity or mortality. The original report also showed that the mortality rate of COVID-19 in breast cancer patients is more dependent on comorbidities than previous radiation therapy or current anti-cancer therapy. However, no meta-analysis has focused on this aspect. This systematic review aims to assess whether breast cancer will increase the severity and mortality of patients infected with COVID-19 and to explore which factors that may affect the severity or mortality rate of breast cancer patients with COVID-19. METHODS: We will search the PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Wanfang database from December 1, 2019 to June 30, 2020. Cohort studies comparing the disease severity and mortality of COVID-19 patients with and without breast cancer will be included. Two independent reviewers will assess the risk of bias of the included cohort studies using the modified Newcastle-Ottawa Scale. We will conduct meta-analyses to calculate the risk ratio (RR) and 95% confidence interval (95% CI) using the random-effects model with the Mantel-Haenszel method. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will be used to rate the quality of the evidence. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will provide comprehensive evidence for medical staff to adopt effective treatment strategies for breast cancer patients during the COVID-19 pandemic. PROSPERO REGISTRATION NUMBER: CRD42020188208.

Diagnostic value of seven biomarkers for breast cancer: an overview with evidence mapping and indirect comparisons of diagnostic test accuracy.

Several meta-analyses have evaluated the value of biomarkers in diagnosing breast cancer, but which biomarker has the optimal diagnostic value remains unclear. This overview aimed to compare the accuracy of different biomarkers in diagnosing breast cancer. PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science were searched. The assessment of multiple systematic reviews-2 (AMSTAR-2) was used to assess the methodological quality and preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy (PRISMA-DTA) for reporting quality. Pairwise meta-analyses were performed to estimate the pooled results for each biomarker, and indirect comparisons were conducted to compare diagnostic accuracy between biomarkers. Eleven systematic reviews (SRs) involving 218 original studies were included. All SRs were of critically low methodological quality, 3 SRs had minimal reporting flaws and 8 SRs had minor flaws. The pooled sensitivity and specificity were 0.77 and 0.87 for miRNA, 0.70 and 0.87 for circulating cell-free DNA, 0.29 and 0.96 for APC gene promoter methylation, 0.69 and 0.99 for 14-3-3σ promoter methylation, 0.63 and 0.82 for CA153, 0.58 and 0.87 for CEA, and 0.73 and 0.56 for PSA. Compared with CA153 and PSA, miRNA had a higher sensitivity and specificity. The sensitivity of miRNA was higher than circulating cell-free DNA and CEA, although they had the same specificities. APC gene promoter methylation and 14-3-3σ promoter methylation were more specific than miRNA, but they had unacceptably low sensitivity. In conclusion, miRNA had better diagnostic accuracy than the other six biomarkers. But due to the low quality of included SRs, the results need to be interpreted with caution. Further study should investigate the diagnostic accuracy of different biomarkers in direct comparisons and focus on the value of combined biomarkers.

An overview protocol of biomarkers for breast cancer detection.

BACKGROUND: Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death over 100 countries. Generally, the prognosis of early-stage breast cancer is good. However, the prognosis is very poor when the disease is diagnosed at an advanced stage. Many screening methods have been used for early detection of breast cancer, but there are some limitations of these methods. Recently, some systematic reviews have evaluated the value of biomarkers for detecting breast cancer. However, most of the systematic reviews (SRs) only evaluated the diagnostic value of 1 biomarker, and it is unclear which biomarker is the best diagnostic test for breast cancer. This overview aims to assess the methodological and reporting quality of available systematic reviews and to compare the diagnostic value of different biomarkers. METHODS: PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science were searched to identify published systematic reviews reporting the value of biomarkers for detecting breast cancer. Title and abstracts, as well as full texts, were screened in duplicate based on inclusion and exclusion criteria. The Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool and Preferred Reporting Items for Systematic Reviews and Meta-analysis diagnostic test accuracy (PRISMA-DTA) checklist will be used to assess the methodological and reporting quality, respectively. We will conduct the pairwise meta-analysis and indirect comparisons using STATA 13.0. RESULTS: The results of this study will be published in a peer-reviewed journal CONCLUSION:: This overview will provide comprehensive evidence of different biomarkers for the diagnosis of breast cancer. PROSPERO REGISTRATION NUMBER: CRD42019125880.

HIV transmission networks among transgender women in Los Angeles County, CA, USA: a phylogenetic analysis of surveillance data.

BACKGROUND: Transgender women are among the groups at highest risk for HIV infection, with a prevalence of 27·7% in the USA; and despite this known high risk, undiagnosed infection is common in this population. We set out to identify transgender women and their partners in a molecular transmission network to prioritise public health activities. METHODS: Since 2006, HIV protease and reverse transcriptase gene (pol) sequences from drug resistance testing have been reported to the Los Angeles County Department of Public Health and linked to demographic data, gender, and HIV transmission risk factor data for each case in the enhanced HIV/AIDS Reporting System. We reconstructed a molecular transmission network by use of HIV-TRAnsmission Cluster Engine (with a pairwise genetic distance threshold of 0·015 substitutions per site) from the earliest pol sequences from 22 398 unique individuals, including 412 (2%) self-identified transgender women. We examined the possible predictors of clustering with multivariate logistic regression. We characterised the genetically linked partners of transgender women and calculated assortativity (the tendency for people to link to other people with the same attributes) for each transmission risk group. FINDINGS: 8133 (36·3%) of 22 398 individuals clustered in the network across 1722 molecular transmission clusters. Transgender women who indicated a sexual risk factor clustered at the highest frequency in the network, with 147 (43%) of 345 being linked to at least one other person (adjusted odds ratio [aOR] 2·0, p=0·0002). Transgender women were assortative in the network (assortativity 0·06, p<0·001), indicating that they tended to link to other transgender women. Transgender women were more likely than expected to link to other transgender women (OR 4·65, p<0·001) and cisgender men who did not identify as men who have sex with men (MSM; OR 1·53, p<0·001). Transgender women were less likely than expected to link to MSM (OR 0·75, p<0·001), despite the high prevalence of HIV among MSM. Transgender women were distributed across 126 clusters, and cisgender individuals linked to one transgender woman were 9·2 times more likely to link to a second transgender woman than other individuals in the surveillance database. Reconstruction of the transmission network is limited by sample availability, but sequences were available for more than 40% of diagnoses. INTERPRETATION: Clustering of transgender women and the observed tendency for linkage with cisgender men who did not identify as MSM, shows the potential to use molecular epidemiology both to identify clusters that are likely to include undiagnosed transgender women with HIV and to improve the targeting of public health prevention and treatment services to transgender women. FUNDING: California HIV and AIDS Research Program and National Institutes of Health-National Institute of Allergy and Infectious Diseases.

Molecular and phylogenetic analyses of a new amphotropic murine leukemia virus (MuLV-1313).

BACKGROUND: The amphotropic murine leukemia viruses (MuLV-A's) are naturally occurring, exogenously acquired gammaretroviruses that are indigenous to the Southern California wild mice. These viruses replicate in a wide range of cell types including human cells in vitro and they can cause both hematological and neurological disorders in feral as well as in the inbred laboratory mice. Since MuLV-A's also exhibit discrete interference and neutralization properties, the envelope proteins of these viruses have been extremely useful for studying virus-host cell interactions and as vehicles for transfer of foreign genes into a variety of hosts including human cells. However, the genomic structure of any of the several known MuLV-A's has not been established and the evolutionary relationship of amphotropic retroviruses to the numerous exogenous or endogenous MuLV strains remains elusive. Herein we present a complete genetic structure of a novel amphotropic virus designated MuLV-1313 and demonstrate that this retrovirus together with other MuLV-A's belongs to a distinct molecular, biological and phylogenetic class among the MuLV strains isolated from a large number of the laboratory inbred or feral mice. RESULTS: The host range of MuLV-1313 is similar to the previously isolated MuLV-A's except that this virus replicates efficiently in mammalian as well as in chicken cells. Compared to ENV proteins of other MuLV-A's (4070A, 1504A and 10A-1), the gp70 protein of MuLV-1313 exhibits differences in its signal peptides and the proline-rich hinge regions. However, the MuLV-1313 envelope protein is totally unrelated to those present in a broad range of murine retroviruses that have been isolated from various inbred and feral mice globally. Genetic analysis of the entire MuLV-1313 genome by dot plot analyses, which compares each nucleotide of one genome with the corresponding nucleotide of another, revealed that the genome of this virus, with the exception of the env gene, is more closely related to the biologically distinct wild mouse ecotropic retrovirus (Cas-Br-E) isolated from another region of the Southern California, than to any of the 15 MuLV strains whose full-length sequences are present in the GenBank. This finding was corroborated by phylogenetic analyses and hierarchical clustering of the entire genomic sequence of MuLV-1313, which also placed all MULV-A's in a genetically distinct category among the large family of retroviruses isolated from numerous mouse strains globally. Likewise, construction of separate dendrograms for each of the Gag, Pol and Env proteins of MuLV-1313 demonstrated that the amphotropic retroviruses belong to a phylogenetically exclusive group of gammaretroviruses compared to all known MuLV strains. CONCLUSION: The molecular, biological and phylogenetic properties of amphotropic retroviruses including MuLV-1313 are distinct compared to a large family of exogenously- or endogenously-transmitted ecotropic, polytropic and xenotropic MuLV strains of the laboratory and feral mice. Further, both the naturally occurring amphotropic and a biologically discrete ecotropic retrovirus of the Southern California wild mice are more closely related to each other on the evolutionary tree than any other mammalian gammaretrovirus indicating a common origin of these viruses. This is the first report of a complete genomic analysis of a unique group of phylogenetically distinct amphotropic virus.

Using laboratory surveillance data to estimate engagement in care among persons living with HIV in Los Angeles County, 2009.

Poor engagement in HIV care has been associated with delayed access to antiretroviral treatment and increased HIV transmission. Using viral load (VL) results from HIV laboratory surveillance data to conduct longitudinal and cross-sectional analyses, we examined linkage to care, retention in care, and their associated factors in 37,325 persons living with HIV (PLWH) in Los Angeles County (LAC). Linkage to care was considered timely if a VL test result was present ≤3 months of diagnosis. Successful retention in care was defined as having two or more VL test results ≥90 days apart during 2009. Of 6841 persons newly diagnosed with HIV in 2007-2009, 67% were linked to care within 3 months of diagnosis. Factors associated with delayed linkage to care included being African American, Latino, and Asian/Pacific Islander (adjusted hazard ratio [AHR]=0.81; 95% CI=0.75-0.87, AHR=0.83; 95% CI=0.77-0.89, AHR=0.82; 95% CI=0.71-0.94, respectively). Of the 37,325 PLWH, 52% were retained in care during 2009. Factors associated with lack of retention in care included injection drug use (adjusted prevalence ratio [APR]=0.88; 95% CI=0.84-0.93), incarceration at diagnosis (APR=0.56; 95% CI=0.51-0.61), being diagnosed in pre-highly active antiretroviral therapy (HAART) era (APR=0.94; 95% CI=0.92-0.96) or at a public facility (APR=0.97; 95% CI=0.95-1.00), age <45 years (APR=0.87; 95% CI=0.86-0.89), and having concurrent HIV/AIDS diagnoses (APR=0.94; 95% CI=0.92-0.96). This study demonstrates the value of using VL surveillance data to monitor engagement in care among PLWH, and its potential to improve linkage and retention efforts where disparities in care are observed.