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.

Prevalence and circulation patterns of variant, atypical and resistant HIV in Los Angeles County (2007-2009).

The prevalence of transmitted HIV drug resistance (TDR) in Los Angeles County remains unknown, due in part to the absence of reliable genotypic data. The specific objectives of this study are to estimate the prevalence of TDR, to describe the demographic characteristics associated with TDR and to investigate the distribution of HIV-1 subtypes among persons newly diagnosed with HIV in Los Angeles County. From 2007 through 2009, 1,414 sequences were obtained from 7,100 persons newly diagnosed with HIV through HIV resistance surveillance. Overall, 257 (18%) sequences had some genetic evidence of drug resistance. Of these, 122 (9%) exhibited evidence of resistance to non-nucleoside reverse transcriptase inhibitors, 121 (9%) to nucleoside reverse transcriptase inhibitors and 76 (5%) to protease inhibitors. Subtype B was dominant (97%), followed by subtypes C (1.2%), CRF01_AE (0.8%), CRF02_AG (0.4%), A (0.3%), and F (0.1%). With a TDR prevalence of 18%, Los Angeles County ranks high compared with other jurisdictions across the nation. The prevalence of TDR in recent (19%) and long-standing (17%) HIV cases were similar, thus providing additional support for the notion that TDR-associated mutations may persist well beyond the period of recent infection. HIV-1 CRF01_AE, observed historically in central Africa and Asia, was observed to be circulating among men who have sex with men and heterosexuals in Los Angeles County. These findings underscore the need for continued and expanded HIV resistance surveillance to inform healthcare providers, policy makers and at-risk populations of emerging trends in HIV drug resistance.

Late HIV detection among adult males in Los Angeles County, 2000-2004.

We analyzed HIV surveillance data on white, black, and Latino males diagnosed with HIV between 2000 and 2004 in Los Angeles County (LAC) to identify associations between individual- and community-level factors and late HIV detection by race/ethnicity. We defined late HIV detection as an AIDS diagnosis within 6 months of HIV diagnosis. We conducted multilevel analysis to determine individual- and community-level risk factors associated with late HIV detection stratified by race/ethnicity. We mapped HIV-positive males with late HIV detection by race/ethnicity at the zip code level within LAC to determine high burden areas. Overall, 38% of all males met the definition of late HIV detection. By race/ethnicity, 44% of Latinos, 38% of blacks, and 30% of whites were detected late in their course of HIV infection. Latinos and whites had multiple individual-level risk factors associated with late HIV detection. Among black males, only older age at HIV diagnosis was associated with late HIV detection. The only community-level risk factor associated with late HIV detection was among Latinos living in communities with less than 6% of men who have sex with men (proxy for stigma). Mapping the distribution of late HIV detection showed late detection areas generalized across LAC for Latino males in comparison with white and black males whose maps showed clustered areas of late HIV detection. Analysis and mapping of individual- and community-level risk factors associated with late HIV detection provides an important tool for targeting prevention resources to areas and populations with the highest burden of disease.

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.

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.

Using a Multitest Algorithm to Improve the Positive Predictive Value of Rapid HIV Testing and Linkage to HIV Care in Nonclinical HIV Test Sites.

BACKGROUND: Use of a rapid HIV testing algorithm (RTA) in which all tests are conducted within one client appointment could eliminate off-site confirmatory testing and reduce the number of persons not receiving confirmed results. METHODS: An RTA was implemented in 9 sites in Los Angeles and San Francisco; results of testing at these sites were compared with 23 sites conducting rapid HIV testing with off-site confirmation. RTA clients with reactive results on more than 1 rapid test were considered HIV+ and immediately referred for HIV care. The positive predictive values (PPVs) of a single rapid HIV test and the RTA were calculated compared with laboratory-based confirmatory testing. A Poisson risk regression model was used to assess the effect of RTA on the proportion of HIV+ persons linked to HIV care within 90 days of a reactive rapid test. RESULTS: The PPV of the RTA was 100% compared with 86.4% for a single rapid test. The time between testing and receipt of RTA results was on average 8 days shorter than laboratory-based confirmatory testing. For risk groups other than men who had sex with men, the RTA increased the probability of being in care within 90 days compared with standard testing practice. CONCLUSIONS: The RTA increased the PPV of rapid testing to 100%, giving providers, clients, and HIV counselors timely information about a client's HIV-positive serostatus. Use of RTA could reduce loss to follow-up between testing positive and confirmation and increase the proportion of HIV-infected persons receiving HIV care.

HIV Infection and Linkage to HIV-Related Medical Care in Large Urban Areas in the United States, 2009.

BACKGROUND: Residents of urban areas have accounted for the majority of persons diagnosed with HIV disease in the United States. Linking persons recently diagnosed with HIV to primary medical care is an important indicator in the National HIV/AIDS Strategy. METHODS: We analyzed data reported to the HIV Surveillance System in 18 urban areas in the United States. Standardized executable SAS programs were distributed to determine the number of HIV cases living through 2008, number of HIV cases diagnosed in 2009, and the percentage of those diagnosed in 2009 who had reported CD4 lymphocyte or HIV viral load test results within 3 months of HIV diagnosis. Data were presented by jurisdiction, age group at diagnosis, race/ethnicity, sex at birth, birth country, disease stage, and transmission category. RESULTS: By jurisdiction, the percentage of persons diagnosed in 2009 with at least 1 CD4 or HIV viral load test within 3 months of diagnosis ranged from 48.5% to 92.5% (median: 70.9). The percentage of persons linked to care varied by age group and by racial/ethnic groups. Fourteen of the 18 areas reported that the percentage of persons linked to care was greater than 65%, the baseline measure indicated in the National HIV/AIDS Strategy. CONCLUSIONS: A wide range in percent linked to HIV medical care was observed between residents of 18 urban areas in the United States with noted age and racial disparities. Routine testing and linkage efforts and intensified prevention efforts should be considered to increase access to primary HIV-related medical care.

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.

Epidemiology of HIV infection in large urban areas in the United States.

BACKGROUND: While the U.S. HIV epidemic continues to be primarily concentrated in urban area, local epidemiologic profiles may differ and require different approaches in prevention and treatment efforts. We describe the epidemiology of HIV in large urban areas with the highest HIV burden. METHODS/PRINCIPAL FINDINGS: We used data from national HIV surveillance for 12 metropolitan statistical areas (MSAs) to determine disparities in HIV diagnoses and prevalence and changes over time. Overall, 0.3% to 1% of the MSA populations were living with HIV at the end of 2007. In each MSA, prevalence was >1% among blacks; prevalence was >2% in Miami, New York, and Baltimore. Among Hispanics, prevalence was >1% in New York and Philadelphia. The relative percentage differences in 2007 HIV diagnosis rates, compared to whites, ranged from 239 (San Francisco) to 1239 (Baltimore) for blacks and from 15 (Miami) to 413 (Philadelphia) for Hispanics. The epidemic remains concentrated, with more than 50% of HIV diagnoses in 2007 attributed to male-to-male sexual contact in 7 of the 12 MSAs; heterosexual transmission surpassed or equaled male-to-male sexual transmission in Baltimore, Philadelphia, and Washington, DC. Yet in several MSAs, including Baltimore and Washington, DC, AIDS diagnoses increased among men-who-have sex with men in recent years. CONCLUSIONS/SIGNIFICANCE: These data are useful to identify local drivers of the epidemic and to tailor public health efforts for treatment and prevention services for people living with HIV.