No abstract

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.

Background HIV pretreatment drug resistance (PDR) to NNRTIs in persons initiating ART is increasing in Mexico. Objectives To compare HIV PDR in eight sub-regions of Mexico. Patients and methods A large PDR survey was implemented in Mexico (September 2017–March 2018) across eight sub-regions. All larger clinics (which provide ART to 90% of all initiators) were included, allocating sample size using the probability-proportional-to-size method. Both antiretroviral-naive and prior antiretroviral-exposed persons were included. HIV PDR levels were estimated from pol Sanger sequences obtained at a WHO-designated laboratory. Results A total of 2006 participants were enrolled from 74 clinics. PDR to NNRTIs was higher than to other drug classes (P < 0.0001), crossing the 10% threshold in the North-East, East, South-West and South-East. NNRTI PDR was higher in the South-West (P = 0.02), coinciding with the highest proportion of restarters in this sub-region (14%). We observed higher PDR prevalence to any drug in women compared with men (16.5% versus 12.2%, P = 0.04). After multivariable adjustment, higher NNRTI PDR remained significantly associated with previous antiretroviral exposure in the Centre-North, North-West, South-West and South-East [adjusted OR (aOR): 21, 5, 8 and 25, respectively; P < 0.05]. Genetic network analyses showed high assortativity by sub-region (P < 0.0001), with evidence of drug resistance mutation transmission within local clusters. Conclusions Diversification of the public health response to HIV drug resistance based on sub-regional characteristics could be considered in Mexico. Higher NNRTI PDR levels were associated with poorer regions, suggesting opportunities to strengthen local HIV programmes. Price and licensing negotiations of drug regimens containing integrase inhibitors are warranted.

Our study suggests different NNRTI PDR prevalence and transmission dynamics in three geographical areas of Mexico. Even when increasing trends in efavirenz resistance were observed in the three areas, our observations support that, in a large country such as Mexico, subnational surveillance and locally tailored interventions to address drug resistance may be a reasonable option.

In response to increasing pretreatment drug resistance (PDR), Mexico changed its national antiretroviral treatment (ART) policy, recommending and procuring second-generation integrase strand-transfer inhibitor (INSTI)-based regimens as preferred first-line options since 2019. We present a four-year observational study describing PDR trends across 2017–2020 at the largest HIV diagnosis and primary care center in Mexico City. A total of 6688 baseline protease-reverse transcriptase and 6709 integrase sequences were included. PDR to any drug class was 14.4% (95% CI, 13.6–15.3%). A significant increasing trend for efavirenz/nevirapine PDR was observed (10.3 to 13.6%, p = 0.02). No increase in PDR to second-generation INSTI was observed, remaining under 0.3% across the study period. PDR was strongly associated with prior exposure to ART (aOR: 2.9, 95% CI: 1.9–4.6, p < 0.0001). MSM had higher odds of PDR to efavirenz/nevirapine (aOR: 2.0, 95% CI: 1.0–3.7, p = 0.04), reflecting ongoing transmission of mutations such as K103NS and E138A. ART restarters showed higher representation of cisgender women and injectable drug users, higher age, and lower education level. PDR to dolutegravir/bictegravir remained low in Mexico City, although further surveillance is warranted given the short time of ART optimization. Our study identifies demographic characteristics of groups with higher risk of PDR and lost to follow-up, which may be useful to design differentiated interventions locally.