A National HIV Provider Survey of Antiretroviral Therapy Preferences for Management of Treatment-Naive and Experienced Individuals With Drug Resistance
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PROVIDER: S-EPMC10655941 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
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Project description:IntroductionSimplified HIV treatment guidelines favor integrase strand transfer inhibitors (INSTIs). However, non-infectious comorbidities and co-occurring conditions (i.e. pregnancy) often necessitate individualized antiretroviral therapy (ART) regimens. This study aimed to characterize United States HIV provider strategies for ART selection when faced with concomitant health conditions.MethodsA survey of US HIV providers was conducted using hypothetical patient cases. Standardized clinical case-vignettes were developed and providers were asked to select their preferred regimen. Eleven cases focused on cardiometabolic syndrome, renal dysfunction, weight gain, and pregnancy.Results119 providers responded across all cases (with a median 57 responses [interquartile range 55.5-72] per case), and were primarily Infectious Diseases physicians in academic settings from across the continental United States. Bictegravir/tenofovir alafenamide/emtricitabine was most commonly prescribed for three case-scenarios of cardiometabolic disease (62.3%). Diverse regimens were recommended for a case involving weight gain, with 98.5% switching from dolutegravir plus tenofovir alafenamide/emtricitabine, most commonly to doravirine/tenofovir disoproxil fumarate/lamivudine. Dolutegravir-based regimens were selected in case-scenarios of pregnancy (77.3%), with some use of bictegravir/tenofovir alafenamide/emtricitabine (13.6%). For two case-scenarios renal disease with worsening creatinine clearance to < 30 mL/minute, many providers used lamivudine or emtricitabine in fixed-dose combination (43.3%).ConclusionThis study reveals varied ART approaches for people living with HIV and non-infectious conditions, often diverging from standard regimens. While guidelines provide a framework, providers adapt treatment based on patient needs. Further research is crucial to optimize ART management in these complex situations.
| S-EPMC11871835 | biostudies-literature
Project description:The use of antiretroviral therapy in HIV infected subjects prevents AIDS-related illness and delayed occurrence of death. In Panama, rollout of ART started in 1999 and national coverage has reached 62.8% since then. The objective of this study was to determine the level and patterns of acquired drug resistance mutations of clinical relevance (ADR-CRM) and surveillance drug resistance mutations (SDRMs) from 717 HIV-1 pol gene sequences obtained from 467 ARV drug-experienced and 250 ARV drug-naïve HIV-1 subtypes B infected subjects during 2007-2013, respectively. The overall prevalence of SDRM and of ADR-CRM during the study period was 9.2% and 87.6%, respectively. The majority of subjects with ADR-CRM had a pattern of mutations that confer resistance to at least two classes of ARV inhibitors. The non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations K103N and P225H were more prevalent in both ARV drug-naïve and ARV drug-experienced subjects. The nucleoside reverse transcriptase inhibitor (NRTI) mutation M184V was more frequent in ARV drug-experienced individuals, while T215YFrev and M41L were more frequent in ARV drug-naïve subjects. Prevalence of mutations associated to protease inhibitors (PI) was lower than 4.1% in both types of subjects. Therefore, there is a high level of resistance (>73%) to Efavirenz/Nevirapine, Lamivudine and Azidothymidine in ARV drug-experienced subjects, and an intermediate to high level of resistance (5-10%) to Efavirenz/Nevirapine in ARV drug-naïve subjects. During the study period, we observed an increasing trend in the prevalence of ADR-CRM in subjects under first-line schemes, but not significant changes in the prevalence of SDRM. These results reinforce the paramount importance of a national surveillance system of ADR-CRM and SDRM for national management policies of subjects living with HIV.
| S-EPMC4847863 | biostudies-literature
Project description:BackgroundHIV integrase inhibitor use is limited by low genetic barrier to resistance and possible cross-resistance among representatives of this class of antiretrovirals. The aim of this study was to analyse integrase sequence variability among antiretroviral treatment naive and experienced patients with no prior integrase inhibitor (InI) exposure and investigate development of the InI drug resistance mutations following the virologic failure of the raltegravir containing regimen.MethodsSequencing of HIV-1 integrase region from plasma samples of 80 integrase treatment naive patients and serial samples from 12 patients with observed virologic failure on raltegravir containing treatment whenever plasma vireamia exceeded >50 copies/ml was performed. Drug resistance mutations were called with Stanford DB database and grouped into major and minor variants. For subtyping bootstrapped phylogenetic analysis was used; Bayesian Monte Carlo Marcov Chain (MCMC) model was implemented to infer on the phylogenetic relationships between the serial sequences from patients failing on raltegravir.ResultsMajority of the integrase region sequences were classified as subtype B; the remaining ones being subtype D, C, G, as well as CRF01_AE , CRF02_AG and CRF13_cpx recombinants. No major integrase drug resistance mutations have been observed in InI-treatment naive patients. In 30 (38.5%) cases polymorphic variation with predominance of the E157Q mutation was observed. This mutation was more common among subtype B (26 cases, 54.2%) than non-B sequences (5 cases, 16.7%), p=0.00099, OR: 5.91 (95% CI:1.77-22.63)]. Other variants included L68V, L74IL, T97A, E138D, V151I, R263K. Among 12 (26.1%) raltegravir treated patients treatment failure was observed; major InI drug resistance mutations (G140S, Q148H and N155H, V151I, E92EQ, V151I, G163R) were noted in four of these cases (8.3% of the total InI-treated patients). Time to the development of drug resistance ranged from 2.6 to 16.3 months with mean increase of HIV viral load of 4.34 (95% CI:1.86-6.84) log HIV-RNA copies/ml at the time of emergence of the major mutations. Baseline polymorphisms, including E157Q were not associated with the virologic failure on raltegravir.ConclusionsIn InI treatment naive patients polymorphic integrase sequence variation was common, with no major resistance mutants. In the treatment failing patients selection of drug resistance occurred rapidly and followed the typical drug resistance pathways. Preexisting integrase polymorphisms were not associated with the treatment failure.
| S-EPMC3547692 | biostudies-literature
Project description:ObjectivesDistal leg epidermal nerve fibre density (ENFD) is a validated predictor of small unmyelinated nerve fibre damage and neuropathy risk in HIV infection. As pre-existing damage may increase the risk of neuropathy following antiretroviral (ARV) therapy, particularly when the regimen contains stavudine (d4T), we assessed the relationship between ENFD and various parameters including mitochondrial factors in HIV-infected Thai individuals naïve to ARV therapy.MethodsDistal leg and proximal thigh ENFDs were quantified in HIV-infected Thai individuals without neuropathy prior to randomization to a HIV clinical trial that focused on mitochondrial toxicity issues. We assessed their association with various clinical and immunovirological parameters as well as with peripheral blood mononuclear cell (PBMC) mitochondrial (mt) DNA copies/cell, oxidative phosphorylation (OXPHOS) complex I (CI) and complex IV (CIV) enzyme activities, and mt 8-oxo-deoxyguanine (8-oxo-dG) break frequencies.ResultsIn 132 subjects, the median (interquartile range) ENFD (fibres/mm) values were 21.0 (16.2-26.6) for the distal leg and 31.7 (26.2-40.0) for the proximal thigh. By linear regression, lower CD4 count (P < 0.01), older age (P < 0.01), increased body mass index (BMI) (P = 0.04), increased height (P = 0.02), and higher PBMC OXPHOS activity as measured by CIV activity (P = 0.02) were associated with lower distal leg ENFD.ConclusionsOlder age, increased height, higher BMI, poorer immunological status and higher PBMC OXPHOS activity are associated with lower distal leg ENFD in HIV-infected subjects free of neuropathy prior to initiation of first-time ARV therapy.
| S-EPMC3654839 | biostudies-literature
Project description:ObjectiveTo analyze and compare HIV-1 env sequences from the eye to those from the blood of individuals with uveitis attributed to HIV with the goal of gaining insight into the pathogenesis of HIV-associated eye disease.DesignA prospective case series of five HIV-infected antiretroviral-naive individuals with uveitis negative for other pathogens.MethodsRNA from blood plasma and ocular aqueous humor was reverse transcribed using random hexamers. HIV env C2-V5 (HXB2: 6990-7668) sequences were generated by single-genome amplification using nested polymerase chain reaction followed by bidirectional Sanger sequencing. Sequence analyses by Geneious, Geno2Pheno, N-GLYCOSITE, DIVEIN, and HyPhy evaluated relationships between HIV in plasma and aqueous humor.ResultsA median of 20 (range: 13-22) plasma and 15 (range: 9-18) aqueous humor sequences were generated from each individual. The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients. Aqueous humor sequences had lower median genetic diversity compared with plasma across all patients, but similar divergence, in four of five patients. Aqueous humor HIV sequences were compartmentalized from plasma across subjects by Critchlow correlation coefficient, Slatkin and Maddison, nearest-neighbor statistic, and Fixation index.ConclusionAmong antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
| S-EPMC5529222 | biostudies-literature
Project description:Memory CD4 T cells are the primary targets of HIV-1 infection, which then subsequently spreads to other T lymphocyte subsets. Antiretroviral therapy (ART) alters the pattern of HIV-1 distribution. Blood samples were collected from ART-naïve or -experienced HIV-1 patients, and the memory and naïve subsets of CD4(+) and CD8(+) T lymphocytes, respectively, were isolated by cell sorting. DNA was extracted and the HIV-1 env C2/V3 region PCR amplified. Amplicons were cloned and sequenced, and genetic relatedness among different HIV-1 compartments was determined by the phylogenetic analysis of clonal sequences. The viral V3 sequence of HIV-1 in each compartment was analyzed by using webPSSM to determine CCR5 or CXCR4 coreceptor binding property of the virus. The direction of viral migration among involved compartments was determined by using the MacClade program. In ART-naïve patients, HIV-1 was generally confined to the memory CD4 T (mT4) cell compartment, even though in a few cases, naïve CD4 T (nT4) cells were also infected. When this occurred, the HIV-1 gene migrated from nT4 to mT4. In contrast, HIV-1 was detected in nT4 and mT4 as well as in the memory CD8 T (mT8) compartments of ART-experienced patients. However, no clear pattern of directional HIV-1 gene flow among the compartments could be determined because of the small sample size. All HIV-1-infected T cell compartments housed the virus that used either CCR5 or CXCR4 as the coreceptor.
| S-EPMC3065334 | biostudies-literature
Project description:To evaluate associations between traditional cardiovascular disease (CVD) risk factors, inflammatory markers and markers of HIV disease activity with ultrasonographic measures of CVD risk in patients with HIV who are not receiving antiretroviral therapy (ART).Cross-sectional, baseline evaluation of ART-naive HIV-infected individuals without known CVD or diabetes mellitus enrolled in a randomized ART treatment trial.Prior to ART initiation, carotid artery intima-media thickness (CIMT) and brachial artery flow-mediated dilation (FMD) were measured. Additional parameters included CD4 cell count, HIV viral load, body composition, lipoproteins and inflammatory markers. Associations with common CIMT, bifurcation CIMT, presence of carotid artery lesions and brachial artery FMD were evaluated.The 331 enrolled individuals were a median (first-third quartile) of 36 (28-45) years old. Common and bifurcation CIMT values were higher and lesions more prevalent with older age (P?<?0.001). FMD was lower with older age (P?=?0.009). Those with a Framingham Risk Score of at least 6% per 10 years (N?=?44) had higher common and bifurcation CIMT (P?<?0.001), carotid lesion prevalence (P?<?0.001) and lower FMD (P?=?0.035). Independent associations with common CIMT were identified for increasing age, height, weight, small low-density lipoprotein (LDL) particles and black race; these were similar for bifurcation CIMT. Presence of carotid artery lesions was associated with increasing age, presence of metabolic syndrome, interleukin-6 and lower HIV-1 RNA.In a contemporary cohort of ART-naive HIV-infected individuals, ultrasonographic measures of CVD risk were more strongly associated with traditional risk factors than CD4 cell counts, HIV replication or inflammatory markers.
| S-EPMC3664137 | biostudies-other
Project description:BackgroundThe presence of HBV resistance mutations upon initiation or during antiretroviral therapy (ART) in HIV-coinfected patients is an important determinant of treatment response. The main objective of the study was to determine the prevalence of HBV resistance mutations in antiretroviral treatment-naive and treatment-experienced HBV-HIV-coinfected Ghanaian patients with detectable HBV viraemia.MethodsHBV-HIV-coinfected patients who were ART-naive or had received at least 9 months of lamivudine (3TC)-containing ART were enrolled in a cross-sectional study. Demographic and clinical data were collected and HBV DNA quantified. Partial HBV sequences were amplified by PCR and sequenced bi-directionally to obtain a 2.1-2.2 kb fragment for phylogenetic analysis of HBV genotypes and evaluation of drug resistance mutations.ResultsOf the 100 HBV-HIV-coinfected study patients, 75 were successfully PCR-amplified, and 63 were successfully sequenced. Of these 63 patients, 27 (42.9%) were ART-experienced and 58 (92.1%) had HBV genotype E. No resistance mutations were observed in the 36 ART-naive patients, while 21 (77.8%) of 27 treatment-experienced patients had resistance mutations. All patients with resistance mutations had no tenofovir in their regimens, and 80% of them had HIV RNA <40 copies/ml. The 3TC resistance mutations rtL180M and rtM204V were observed in 10 (47.6%) of the 21 patients, while 5 patients (23.8%) had rtV173L, rtL180M and rtM204V mutations.ConclusionsA high proportion of HBV-HIV-coinfected patients with detectable viraemia on 3TC-containing ART had resistance mutations despite good ART adherence as determined by HIV RNA suppression. This study emphasizes the need for dual therapy as part of a fully suppressive ART in all HBV-HIV-coinfected patients in Ghana.
| S-EPMC5106338 | biostudies-literature
Project description:ObjectivesA national survey evaluated the availability of naltrexone as a treatment for alcohol use disorder and/or opioid use disorder for pregnant individuals. Provider perceptions of barriers to treatment with naltrexone during pregnancy were also examined.MethodsSites were selected from a national registry of naltrexone prescribers (N = 5208). A 10% sampling of sites within 150 miles of each state's capital was selected (n = 2073). Survey of 11 questions included availability of naltrexone for pregnant individuals, standard practices for treating pregnant individuals already on naltrexone, and barriers to treatment. Survey responses were summarized to identify top barriers and national trends in service availability.ResultsOf the 236 sites contacted, 78 (33.1%) completed the survey. There was significant geographic variation in number of available sites, with Northeast United States having the most sites. Of the 78 responding sites, only 23 (35.9%) offered naltrexone for pregnant individuals. The most common barriers to prescribing naltrexone included the following: sites without pregnant patients (15.6%), lack of national guidelines in using naltrexone for pregnant patients (14.1%), providers' discomfort with prescribing naltrexone during pregnancy due to safety concerns (9.4%), and providers' discomfort due to inexperience (4.7%).ConclusionsAccessibility of naltrexone and related care for pregnant individuals with alcohol use disorder and opioid use disorder varies greatly across the United States with numerous barriers and educational gaps identified. Additional research and resources are needed to expand naltrexone treatment access for pregnant individuals.
| S-EPMC10873530 | biostudies-literature
Project description:BACKGROUND:The presence of drug resistance mutations (DRMs) against antiretroviral agents is one of the main concerns in the clinical management of individuals with human immunodeficiency virus-1 (HIV-1) infection, especially in regions of the world where treatment options are limited. The current study aimed at assessing the prevalence of HIV-1 DRMs among naïve and treatment-experienced HIV-1-infected patients in Iran. METHODS:From April 2013 to September 2018, the HIV-1 protease and reverse transcriptase genes were amplified and sequenced in plasma specimens of 60 newly diagnosed antiretroviral-naive individuals and 46 participants receiving antiretroviral therapies (ARTs) for at least six months with an HIV viral load of more than 1000 IU/mL to determine the HIV-1 DRMs and subtypes. RESULTS:Among the 60 treatment-naïve HIV-1-infected participants, 8.3% were infected with HIV-1 variants with surveillance DRMs (SDRMs). The SDRMs, D67N and D67E, belonged to the NRTIs class in two patients and K103N and V106A belonged to the NNRTIs class in three patients. The phylogenetic analysis showed that 91.7% of the subjects were infected with subtype CRF35_AD, followed by subtype B (5.0%) and CRF01_AE (3.3%). Among the 46 ART-experienced participants, 33 (71.7%) carried HIV-1 variants with SDRMs (9.1% against PIs, 78.8% against NRTIs, and 100% against NNRTIs). M46I and I47V were the most common mutations for PIs, M184V was the most common mutation for the NRTIs, and K103N/S was the most common mutation for NNRTIs. Phylogenetic analysis of the polymerase region showed that all of the 46 HIV-1-infected patients who failed on ART carried CRF35_AD. CONCLUSIONS:The moderate prevalence of SDRMs (8.3%) in treatment-naïve and ART-failed (77.1%) Iranian patients with HIV-1-infection emphasizes the need for systematic viral load monitoring, expanding drug resistance testing, carefully surveilling individuals on ART regimens, and facilitating access to new antiretrovirals by health authorities.
| S-EPMC7051075 | biostudies-literature