ObjectiveThe Honduran HIV/AIDS Program began to scale up access to HIV therapy in 2002. Up to May 2008, more than 6000 patients received combination antiretroviral therapy (cART). As HIV drug resistance is the major obstacle for effective treatment, the purpose of this study was to assess the prevalence of antiretroviral drug resistance in Honduran HIV-1-infected individuals. MethodsWe collected samples from 138 individuals (97 adults and 41 children) on cART with virological, immunological or clinical signs of treatment failure. HIV-1 pol sequences were obtained using an in-house method. Resistance mutations were identified according to the 2007 International AIDS Society (IAS)-USA list and predicted susceptibility to cART was scored using the ANRS algorithm. ResultsResistance mutations were detected in 112 patients (81%), 74% in adults and 98% in children. Triple-, dual-and single-class drug resistance was documented in 27%, 43% and 11% of the study subjects, respectively. Multiple logistic regression showed that resistance was independently associated with type of treatment failure [virological failure (odds ratio (OR) 5 1) vs. immunological failure (OR 5 0.11; 95% confidence interval (CI) 0.030-0.43) vs. clinical failure (OR 5 0.037; 95% CI 0.0063-0.22)], route of transmission (OR 5 42.8;, and years on therapy (OR 5 1.81; 95% CI 1.11-2.93). ConclusionThe prevalence of antiretroviral resistance was high in Honduran HIV-infected patients with signs of treatment failure. A majority of study subjects showed dual-or triple-class resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Virologically defined treatment failure was a strong predictor of resistance, indicating that viral load testing is needed to correctly identify patients with treatment failure attributable to resistance.Keywords: antiretroviral treatment, drug resistance, HIV, mutations, treatment failure IntroductionThe mortality of HIV-1 infection has decreased dramatically in the developed parts of the world following the introduction of combination antiretroviral therapy (cART) in 1996 [1][2][3]. cART typically involves therapy with two Honduras is estimated to have one of the highest HIV-1 prevalences (0.7%; range 0.4-1.4%) in Latin America [6].Of the large number of HIV-positive individuals, 12 000 are estimated to be in need of cART (Table 1). The National HIV/AIDS Program in Honduras began to scale up access to therapy in 2002, and since then many patients have gained access to cART. At present approximately 6000 patients have been under treatment, of whom around 700 have interrupted therapy and more than 800 have died [7].The goal of modern cART is to suppress viral replication and maintain plasma HIV-1 RNA levels in treated patients below the detection limit of sensitive assays (i.e. o50 HIV-1 RNA copies/mL plasma) [3,4]. Treatment failure during cART is a significant clinical problem. Poor adherence is the most common cause of treatment failure, but failure can al...
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.
The Honduran Ministry of Health (MOH) HIV antiretroviral treatment program began widespread treatment in 2003. We investigated the prevalence of antiretroviral genotypic resistance in specimens collected and archived from HIV-1-infected antiretroviral-naive patients presenting to initiate treatment between 1 July, 2002 and 30 June, 2003 in San Pedro Sula and Tegucigalpa, Honduras. Of 416 specimens collected, 336 (80.8%) were successfully genotyped. All genotypes were HIV-1, group M and 99.1% were subtype B. The prevalence of nucleoside reverse transcriptase inhibitor mutations was 7.7% with M184V and T215F/Y present in 6.0% and 3.0%, respectively. The prevalence of nonnucleoside reverse transcriptase inhibitor mutations was 7.1%. K103N mutations were present in 3.0% of study specimens. The prevalence of major protease inhibitor mutations was 2.7%. Overall, 9.2% of the specimens harbored clinically significant mutations that predict at least intermediate resistance to the Honduran first-line antiretroviral medications. These mutations were more common in San Pedro Sula (14.0%) than in Tegucigalpa (6.5%, p = 0.02). A significant number of patients presenting to initiate antiretroviral therapy in Honduran MOH clinics harbored HIV-1 isolates resistant to the MOH's first-line regimen and resistance varied by region. Further studies to assess the impact of the Honduran antiretroviral program on genotypic resistance are warranted.
Background: Mucormycosis is a life-threatening invasive fungal infection most commonly observed in immunocompromised patients. Throughout the COVID-19 pandemic, a growing number of Mucorales associated infections, now termed COVID-19 associated mucormycosis (CAM), have been reported. Despite an increase in fatality reports, no cases of rhino-orbital CAM complicated with gangrenous bone necrosis have been described in the literature to date. Case: A 56-year-old male with a recent COVID-19 diagnosis developed rhino-orbital mucormycosis after 22 days of treatment with dexamethasone. Cultures and histopathological assessment of tissue biopsy confirmed the diagnosis. The patient survived after treatment with amphotericin B. Conclusions: Mucormycosis is an invasive fungal infection affecting mostly immunocompromised patients. Along with the COVID-19 pandemic, the inappropriate use of steroids, in addition to concurrent risk factors, such as diabetes, has led to an increase in the occurrence of these devastating mycoses, leading to the development of severe presentations and complications, as observed in many cases. Early diagnosis and prompt treatment are crucial in order to avoid dissemination and fatal outcomes.
IntroductionWe assessed HIV drug resistance (DR) in individuals failing ART (acquired DR, ADR) and in ART-naïve individuals (pre-ART DR, PDR) in Honduras, after 10 years of widespread availability of ART.Methods365 HIV-infected, ART-naïve, and 381 ART-experienced Honduran individuals were enrolled in 5 reference centres in Tegucigalpa, San Pedro Sula, La Ceiba, and Choluteca between April 2013 and April 2015. Plasma HIV protease-RT sequences were obtained. HIVDR was assessed using the WHO HIVDR mutation list and the Stanford algorithm. Recently infected (RI) individuals were identified using a multi-assay algorithm.ResultsPDR to any ARV drug was 11.5% (95% CI 8.4–15.2%). NNRTI PDR prevalence (8.2%) was higher than NRTI (2.2%) and PI (1.9%, p<0.0001). No significant trends in time were observed when comparing 2013 and 2014, when using a moving average approach along the study period or when comparing individuals with >500 vs. <350 CD4+ T cells/μL. PDR in recently infected individuals was 13.6%, showing no significant difference with PDR in individuals with longstanding infection (10.7%). The most prevalent PDR mutations were M46IL (1.4%), T215 revertants (0.5%), and K103NS (5.5%). The overall ADR prevalence in individuals with <48 months on ART was 87.8% and for the ≥48 months on ART group 81.3%. ADR to three drug families increased in individuals with longer time on ART (p = 0.0343). M184V and K103N were the most frequent ADR mutations. PDR mutation frequency correlated with ADR mutation frequency for PI and NNRTI (p<0.01), but not for NRTI. Clusters of viruses were observed suggesting transmission of HIVDR both from ART-experienced to ART-naïve individuals and between ART-naïve individuals.ConclusionsThe global PDR prevalence in Honduras remains at the intermediate level, after 10 years of widespread availability of ART. Evidence of ADR influencing the presence of PDR was observed by phylogenetic analyses and ADR/PDR mutation frequency correlations.
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