Novel HLA class I associations with HIV-1 control in a unique genetically admixed population.

Associations between HLA class I alleles and HIV progression in populations exhibiting Amerindian and Caucasian genetic admixture remain understudied. Using univariable and multivariable analyses we evaluated HLA associations with five HIV clinical parameters in 3,213 HIV clade B-infected, ART-naïve individuals from Mexico and Central America (MEX/CAM cohort). A Canadian cohort (HOMER, n = 1622) was used for comparison. As expected, HLA allele frequencies in MEX/CAM and HOMER differed markedly. In MEX/CAM, 13 HLA-A, 24 HLA-B, and 14 HLA-C alleles were significantly associated with at least one clinical parameter. These included previously described protective (e.g. B*27:05, B*57:01/02/03 and B*58:01) and risk (e.g. B*35:02) alleles, as well as novel ones (e.g. A*03:01, B*15:39 and B*39:02 identified as protective, and A*68:03/05, B*15:30, B*35:12/14, B*39:01/06, B*39:05~C*07:02, and B*40:01~C*03:04 identified as risk). Interestingly, both protective (e.g. B*39:02) and risk (e.g. B*39:01/05/06) subtypes were identified within the common and genetically diverse HLA-B*39 allele group, characteristic to Amerindian populations. While HLA-HIV associations identified in MEX and CAM separately were similar overall (Spearman's rho = 0.33, p = 0.03), region-specific associations were also noted. The identification of both canonical and novel HLA/HIV associations provides a first step towards improved understanding of HIV immune control among unique and understudied Mestizo populations.

Identification of major routes of HIV transmission throughout Mesoamerica.

BACKGROUND: Migration and travel are major drivers of the spread of infectious diseases. Geographic proximity and a common language facilitate travel and migration in Mesoamerica, which in turn could affect the spread of HIV in the region. METHODS: 6092 HIV-1 subtype B partial pol sequences sampled from unique antiretroviral treatment-naïve individuals from Mexico (40.7%), Guatemala (24.4%), Honduras (19%), Panama (8.2%), Nicaragua (5.5%), Belize (1.4%), and El Salvador (0.7%) between 2011 and 2016 were included. Phylogenetic and genetic network analyses were performed to infer putative relationships between HIV sequences. The demographic and geographic associations with clustering were analyzed and viral migration patterns were inferred using the Slatkin-Maddison approach on 100 iterations of random subsets of equal number of sequences per location. RESULTS: A total of 1685/6088 (27.7%) of sequences linked with at least one other sequence, forming 603 putative transmission clusters (range: 2-89 individuals). Clustering individuals were significantly more likely to be younger (median age 29 vs 33years, p<0.01) and men-who-have-sex-with-men (40.4% vs 30.3%, p<0.01). Of the 603 clusters, 30 (5%) included sequences from multiple countries with commonly observed linkages between Mexican and Honduran sequences. Eight of the 603 clusters included >10 individuals, including two comprised exclusively of Guatemalans (52 and 89 individuals). Phylogenetic and migration analyses suggested that the Central and Southern regions of Mexico along with Belize were major sources of HIV throughout the region (p<0.01) with genetic flow southward from Mexico to the other nations of Mesoamerica. We also found evidence of significant viral migration within Mexico. CONCLUSION: International clusters were infrequent, suggesting moderate migration between HIV epidemics of the different Mesoamerican countries. Nevertheless, we observed important sources of transnational HIV spread in the region, including Southern and Central Mexico and Belize.

Clinical and demographic features of HIV infection in El Salvador.

OBJECTIVE: To understand some of the clinical and demographic features of the epidemic of infection by HIV in El Salvador prior to the availability of antiretroviral therapy in that country. METHODS: We conducted a retrospective review of HIV-infected individuals who were admitted to Hospital Rosales, which is a large public teaching hospital in San Salvador, El Salvador, during the 5-year period of 1994 through 1998. Chart abstraction was done of 194 out of the 208 individuals admitted to the Infectious Diseases Unit at Hospital Rosales (14 charts could not be located). We also carried out a sampling of other HIV-infected adults treated in other parts of the hospital. RESULTS: Of the 250 patients whose records we reviewed, 67% were men and 86% were from an urban area. The mean age at HIV diagnosis was 34 years. In terms of occupation, 50% of the men were day laborers; 76% of the women were housewives, and 8% of the women were commercial sex workers. All the women studied listed only heterosexual contact as their risk behavior. Of the men, 9% of them said they had sex only with men, 17% said with both men and women, and 65% said with female commercial sex workers. In terms of drug use, 2% of the patients reported they had used injection drugs at some point. At their initial medical visit to Hospital Rosales, over half of the 250 patients presented with a respiratory complaint or with diarrhea, 6% had pulmonary tuberculosis (TB), and 5% had extrapulmonary TB. Of the 250 patients, 177 of them (71%) had AIDS at the first medical visit. Of the 250, 138 of them (55%) were lost to follow-up. Of the remaining 112 persons, 81 of them (72%) were known to have died. Of those 81, 38 of them (47%) died of unknown causes and 21 (26%) died of TB. CONCLUSIONS: The HIV-infected adults treated at the Hospital Rosales during the 1994-1998 period were usually infected through heterosexual sex, were symptomatic at the time of presentation, and were often lost to follow-up. Utilizing the results of our study and of other research, efforts to expand early intervention, counseling and testing, and targeted prevention activities should be strengthened.

Clinical and demographic features of HIV infection in El Salvador

OBJECTIVE: To understand some of the clinical and demographic features of the epidemic of infection by HIV in El Salvador prior to the availability of antiretroviral therapy in that country. METHODS: We conducted a retrospective review of HIV-infected individuals who were admitted to Hospital Rosales, which is a large public teaching hospital in San Salvador, El Salvador, during the 5-year period of 1994 through 1998. Chart abstraction was done of 194 out of the 208 individuals admitted to the Infectious Diseases Unit at Hospital Rosales (14 charts could not be located). We also carried out a sampling of other HIV-infected adults treated in other parts of the hospital. RESULTS: Of the 250 patients whose records we reviewed, 67 percent were men and 86 percent were from an urban area. The mean age at HIV diagnosis was 34 years. In terms of occupation, 50 percent of the men were day laborers; 76 percent of the women were housewives, and 8 percent of the women were commercial sex workers. All the women studied listed only heterosexual contact as their risk behavior. Of the men, 9 percent of them said they had sex only with men, 17 percent said with both men and women, and 65 percent said with female commercial sex workers. In terms of drug use, 2 percent of the patients reported they had used injection drugs at some point. At their initial medical visit to Hospital Rosales, over half of the 250 patients presented with a respiratory complaint or with diarrhea, 6 percent had pulmonary tuberculosis (TB), and 5 percent had extrapulmonary TB. Of the 250 patients, 177 of them (71 percent) had AIDS at the first medical visit. Of the 250, 138 of them (55 percent) were lost to follow-up. Of the remaining 112 persons, 81 of them (72 percent) were known to have died. Of those 81, 38 of them (47 percent) died of unknown causes and 21 (26 percent) died of TB. CONCLUSIONS: The HIV-infected adults treated at the Hospital Rosales during the 1994-1998 period were usually infected through heterosexual sex, were symptomatic at the time of presentation, and were often lost to follow-up. Utilizing the results of our study and of other research, efforts to expand early intervention, counseling and testing, and targeted prevention activities should be strengthened