En qué sentido la tesis de Herbert Hart justifica la creación

Many studies have examined geographic or spatial heterogeneity of HIV or STI

diagnoses.36,44,51,52,230 _{On a large scale, the rates of incident HIV diagnoses are much higher in}

the US Northeast and South than the West and the Midwest. Further comparison of the higher rates US Northeast and the US South yields racial differences; in both places, 75% of people living with AIDS were either Black or Hispanic, although Hispanics accounted for a smaller percentage in the US South than in the Northeast.32

On a smaller scale, geographic core areas have been identified for several sexually transmitted infections.33 _{Risk of having primary or secondary syphilis was 4.6 times higher for}

persons living in a certain area of San Francisco between 1985 and 2007. The spatial analysis was able to separate core and outbreak areas.34 _{HIV-positive persons resided closer to their}

partners in Colorado Springs than at risk persons who are not HIV-positive and their partners.35

During a syphilis outbreak in Baltimore, two areas were identified as core areas from which the outbreak spread and a new core area was created. Even after the outbreak ended, density of cases remained higher in all 3 core areas.36 _{Syphilis was found to co-cluster with gonorrhea in}

NC; state-wide mapping of gonorrhea and syphilis over time identified 20 core areas for gonorrhea and 10 for syphilis. All of the syphilis core areas were found to have at least some overlap with at least one gonorrhea core area. All clusters, for gonorrhea and syphilis, were found to be associated with an urban area; some areas existed entirely in urban areas and some encompassed but urban and rural but none were entirely rural.50 _{The rural-urban divide}

has been noted for other STIs in NC. Drug susceptible HIV strains were significantly more genetically similar than drug resistant strains for rural-rural and rural-urban partnerships, but not for urban-urban partnerships. Urbanicity of residence was not associated with TDRM v. drug susceptible virus among persons with acute HIV infection.51 _{Geographically-associated network}

cores have been found to significantly contribute to STI spread,50,52 _{but it is unknown whether}

the same relationship is found with TDRM, particularly in rural areas.

Geographic and spatial investigation of HIV and STI outbreaks in NC has yielded important information. The CDC found that NC had the highest burden of HIV in non-urban areas in 2006.4 _{Figure 1 (section II.A.2.c.), from the 2013 HIV/STD NC Epidemiologic Profile}

report, shows incident and prevalent HIV cases across the state. The largest clusters are in the most urban areas, but the rural eastern part of the state has a high burden of HIV without having as many specialists and providers as the central part of the state.

Spatiotemporal analysis was applied to identify core clusters of gonorrhea and syphilis in NC, with an additional assessment of rurality. All of the syphilis and gonorrhea core areas included at least one urban area, and all of the syphilis core areas (N=10) overlapped with gonorrhea core areas (N=20).50 _{Similarly, in Wake County, a single urban county in central NC,}

chlamydia, gonorrhea, primary and secondary syphilis, and HIV were found to cluster with a single identifiable core area; all four core areas overlapped.53 _{These studies show that in NC,}

there is geographic overlap of several STIs. Without added analysis of the sexual networks, it is unknown whether the STIs are circulating among different groups. As HIV is more easily

transmitted in the presence of certain STIs, future areas of research should include both network and geographic or spatial analysis.

1. Phylogenetic Analysis Combined with Spatial or Geographic Analysis

Gene sequence analysis combined with spatial and geographic analyses have helped trace the spread of HIV around the world through history; looking at virus evolution in different places gives a sense of divergence.230-232 _{The F1 subtype is the second most common HIV-1}

type in Italy, although two distinct clades are seen and its origin was not known until recently. HIV-1 subtype F1 is believed to have arisen in West Africa before arriving in South America in the 1950s. From South America, the F1 subtype spread to Angola.232 _{Subtype C is most}

arrived in Italy in the 1970s directly from South America and indirectly through Angola and Romania before being introduced, which account for the distinct clades seen today.232

Angola is a unique environment. A war for independence from the Portuguese took place from 1961-1975, leading to mass migrations and mixing of groups, just after the time when the F1 variant was introduced from South America. In 1975, the Portuguese conceded and in the same year, a war for independence began between the two most dominant ethnic groups. The civil war lasted until 2002, with movement of troops and civilians throughout the country. Due to lengthy deployments, it was not uncommon for men in the military to have wives in different parts of the country. The civil war factions were split along ethnic lines and traditionally lived in different parts of the country; the creation of the colony of Angola by the Portuguese in the 1500s encompassed groups speaking 7 different Bantu languages. The ethnic group originally granted power in 1975 and currently in power retained the northern and most of the central territory and the “rebel” group retained the southern part of the country.

Subtype F1 would have been introduced just prior to the 1961 start of the war for independence232 _{and its mass migration. Subtype C appears to have been introduced multiple}

times from several different African countries, leading to distinct lineages.233 _{Pol gene subtype}

analysis somewhat follows ethnic lines as they were influenced by the war. Subtype F1 is the predominant strain in the north (20% of sequences analyzed) and subtype C is the predominant strain in the south (46% of sequences analyzed). The central part of the country is dominated by recombinants (42% of sequences analyzed).234 _{Combining geographic and phylogenetic}

data can indicate the presence of historical or contextual reasons why groups with similarities in a contained area don’t cluster.

US-born and foreign-born Latinos with acute HIV in NC did not cluster with each other and appeared to have distinct sexual networks; US-born Latinos were more likely to cluster with Black persons.49 _{Therefore, adding the genetic data to the geographic data showed that despite}

important to recognize for the present study, as 12.8% of persons living in Wake County from 2009-2013 were foreign-born.235