Long-term ART Research Articles

Exploring diseases burden in HIV population: Results from the CHAO (Comorbidities in HIV/AIDS outpatients) cross-sectional study in Kenya

BackgroundAfrica is the epicenter of the HIV epidemic, with over two-thirds of the global population living with HIV. It is also facing a dramatic increase in non-communicable diseases (NCDs) amidst its aging population. This necessitates a healthcare approach that addresses both infectious diseases and NCDs in HIV-positive individuals. In Kenya, with 1.4 million HIV-positive people, efforts include widespread ART access and integrating HIV services into the health system. Challenges remain in healthcare infrastructure, particularly in rural areas. The Comorbidities in HIV/AIDS Outpatients (CHAO) Project, funded by the Italian Cooperation Agency, aims to improve understanding and management of comorbidities in HIV patients, highlighting the need for cost-effective healthcare strategies to address this dual burden. MethodsThe CHAO (Comorbidities in HIV/AIDS Outpatients) project conducted a cross-sectional epidemiological study across 25 clinics in Meru County, Kenya. The study included comprehensive surveys and screenings for various comorbidities among HIV-positive patients receiving treatment, utilizing both clinical evaluations and laboratory tests to assess the prevalence of infectious diseases and NCDs. ResultsA total of 1051 HIV-positive individuals were included in the study: 75 % females, 25 % males, median age 47 years, the majority (96 %) on long-term ART, mostly Dolutegravir-based (95 %). 55.4 % had at least one comorbidity, with NCDs such as dyslipidemia (21.22 %) and hypertension (20.17 %) being the most prevalent. The study also noted significant occurrences of communicable diseases, including syphilis (5.23 %), hepatitis B (2.19 %), and hepatitis C (0.29 %). The prevalence of comorbidities varied with age, highlighting the impact of aging on disease burden. DiscussionThe high prevalence of comorbidities among HIV-positive patients in Meru County underscores the need for integrated healthcare strategies that address both infectious diseases and NCDs. The findings advocate for systematic screening and management of comorbidities within HIV care programs, emphasizing the need for holistic health approaches to improve outcomes for this population.

Mobilising Affect for Public Art: Affective practices in voluntary organising.

Voluntary organising frequently relies on affective intensities to direct organisational efforts. However, it is not well understood how these intensities are cultivated across time and different contexts to engage and coordinate heterogeneous actors. By applying a practice approach to affect, this paper proposes the concept of affective practices to theorise how affect is mobilised in materially driven (inter)actions to shape actions and relationalities around organisational goals. The analysis of ethnographic data from a long-term public art project reveals that four affective practices - enticing, envisioning, attending and asserting - are pivotal to sustaining the distributed process of voluntary organising. The sense of fascination, enthusiasm, care and discomfort that these affective practices mobilise instigates participation, support, acceptance and compliance from diverse partners, volunteers and the local public. Contributing to the affective turn in practice theory, the paper theorises how affective processes are cultivated as situative accomplishments in an ongoing and translocal organisational process, highlighting the important role played by the vibrant presence of matter in affective practices. Additionally, the study expands our understanding of how an interplay of affective intensities engages and aligns diverse individuals and groups in voluntary organising by fostering coalitional moments in the organisational process.

Machine learning approaches identify immunologic signatures of total and intact HIV DNA during long-term antiretroviral therapy.

Understanding the interplay between the HIV reservoir and the host immune system may yield insights into HIV persistence during antiretroviral therapy (ART) and inform strategies for a cure. Here, we applied machine learning approaches to cross-sectional high-parameter HIV reservoir and immunology data in order to characterize host-reservoir associations and generate new hypotheses about HIV reservoir biology. High-dimensional immunophenotyping, quantification of HIV-specific T cell responses, and measurement of genetically intact and total HIV proviral DNA frequencies were performed on peripheral blood samples from 115 people with HIV (PWH) on long-term ART. Analysis demonstrated that both intact and total proviral DNA frequencies were positively correlated with T cell activation and exhaustion. Years of ART and select bifunctional HIV-specific CD4 T cell responses were negatively correlated with the percentage of intact proviruses. A Leave-One-Covariate-Out (LOCO) inference approach identified specific HIV reservoir and clinical-demographic parameters, such as age and biological sex, that were particularly important in predicting immunophenotypes. Overall, immune parameters were more strongly associated with total HIV proviral frequencies than intact proviral frequencies. Uniquely, however, expression of the IL-7 receptor alpha chain (CD127) on CD4 T cells was more strongly correlated with the intact reservoir. Unsupervised dimension reduction analysis identified two main clusters of PWH with distinct immune and reservoir characteristics. Using reservoir correlates identified in these initial analyses, decision tree methods were employed to visualize relationships among multiple immune and clinical-demographic parameters and the HIV reservoir. Finally, using random splits of our data as training-test sets, machine learning algorithms predicted with approximately 70% accuracy whether a given participant had qualitatively high or low levels of total or intact HIV DNA. The techniques described here may be useful for assessing global patterns within the increasingly high-dimensional data used in HIV reservoir and other studies of complex biology.

A specific natural killer cells phenotypic signature associated to long term elite control of HIV infection.

Elite controllers (ECs) are an exceptional group of people living with HIV (PLWH) that control HIV replication without therapy. Among the mechanisms involved in this ability, natural killer (NK)-cells have recently gained much attention. We performed an in-deep phenotypic analysis of NK-cells to search for surrogate markers associated with the long term spontaneous control of HIV. Forty-seven PLWH (22 long-term EC [PLWH-long-term elite controllers(LTECs)], 15 noncontrollers receiving antiretroviral treatment [ART] [PLWH-onART], and 10 noncontrollers cART-naïve [PLWH-offART]), and 20 uninfected controls were included. NK-cells homeostasis was analyzed by spectral flow cytometry using a panel of 15 different markers. Data were analyzed using FCSExpress and R software for unsupervised multidimensional analysis. Six different subsets of NK-cells were defined on the basis of CD16 and CD56 expression, and the multidimensional analysis revealed the existence of 68 different NK-cells clusters based on the expression levels of the 15 different markers. PLWH-offART presented the highest disturbance of NK-cells homeostasis and this was not completely restored by long-term ART. Interestingly, long term spontaneous control of HIV (PLWH-LTEC group) was associated with a specific profile of NK-cells homeostasis disturbance, characterized by an increase of CD16dimCD56dim subset when compared to uninfected controls (UC) group and also to offART and onART groups (p < 0.0001 for the global comparison), an increase of clusters C16 and C26 when compared to UC and onART groups (adjusted p-value < 0.05 for both comparisons), and a decrease of clusters C10 and C20 when compared to all the other groups (adjusted p-value < 0.05 for all comparisons). These findings may provide clues to elucidate markers of innate immunity with a relevant role in the long-term control of HIV.

CRF08_BC subtype is more prone to ART failure and new-generation NNRTI-resistance under long-term first-line ART

ObjectiveTo investigate the characteristics of drug resistance mutations (DRMs) and their contextual influence on drug susceptibility in CRF07_BC and CRF_08BC subtypes. MethodsPatients with virological failure were genotyped using phylogenetic analysis. DRMs and susceptibility to antiretroviral drugs were analysed using the Stanford University HIV Drug Resistance Database. ResultsSix HIV subtypes were identified among 1296 successfully amplified sequences, with the CRF07_BC subtype prevailing at a rate of 91.7%, followed by CRF08_BC. Overall, the CRF07_BC and CRF08_BC subtypes were similar in the distribution and frequency of DRMs, the most common DRMs were K103N and M184V. However, among patients with antiretroviral therapy duration of ≥3 y who developed resistance, CRF08_BC exhibited a higher mutation frequency at sites 184, 138, 221, and 188 (Chi-square test, P < 0.05), and compared with CRF07_BC, patients with CRF08_BC had higher prevalence of abacavir, emtricitabine, lamivudine, doravirine, etravirine, and rilpivirine resistance. Moreover, there was an increased prevalence of cross-resistance between efavirenz/nevirapine and new-generation NNRTIs in patients with CRF08_BC; doravirine (r = 1.0), rilpivirine (r = 0.93), and etravirine (r = 0.86) resistance highly correlated with efavirenz/nevirapine. ConclusionsThe present study provides valuable insights into the profile of DRMs and resistance patterns in patients with CRF07_BC and CRF08_BC experiencing treatment failure in Butuo. These findings have the potential to contribute to future strategies for HIV control and treatment.

Indicators of endocrine function of muscle and fat tissue in athletes participating in martial arts

Purpose of the study: the aim of that study was an investigation of the level of adipokines, myokines and growth factors in the blood of athletes involved in acyclic sports — martial arts.Materials and methods: we have investigated 15 male athletes aged 15–19 years. The control group included 15 healthy men of the same age who did not engage in sports. In the blood serum of the all subjects, leptin, adiponectin, resistin, apelin, irisin, adipsin, myostatin, FGF21, osteocrin and oncostatin were determined using a multiplex analysis.Results: studies have shown that long-term regular martial arts training is accompanied by a decrease in the level of leptin, resistin and oncostatin M in the blood of athletes and a change in correlations between the content of the studied myokines, adipokines and growth factors compared with their values in the control group.Conclusions: regular long-term martial arts training is accompanied by a decrease in the level of leptin, resistin and oncostatin M in the blood of athletes. Their occurrence is associated with changes in the state of regulatory systems that control the production and secretion of myokines, adipokines and growth factors in adipose, muscle, nervous and bone tissue. The resulting shifts ensure adaptation of the athletes’ bodies to physical activity.

Using art as a tool for holistic development

Exploring the benefits of a long-term art project inspired by Paul Klee's Castle and Sun.

Dominant CD4+ T cell receptors remain stable throughout antiretroviral therapy-mediated immune restoration in people with HIV

In people with HIV (PWH), the post-antiretroviral therapy (ART) window is critical for immune restoration and HIV reservoir stabilization. We employ deep immune profiling and Tcell receptor (TCR) sequencing and examine proliferation to assess how ART impacts Tcell homeostasis. In PWH on long-term ART, lymphocyte frequencies and phenotypes are mostly stable. By contrast, broad phenotypic changes in natural killer (NK) cells, γδ Tcells, B cells, and CD4+ and CD8+ Tcells are observed in the post-ART window. Whereas CD8+ Tcells mostly restore, memory CD4+ T subsets and cytolytic NK cells show incomplete restoration 1.4 years post ART. Surprisingly, the hierarchies and frequencies of dominant CD4 TCR clonotypes (0.1%-11% of all CD4+ Tcells) remain stable post ART, suggesting that clonal homeostasis can be independent of homeostatic processes regulating CD4+ Tcell absolute number, phenotypes, and function. The slow restoration of host immunity post ART also has implications for the design of ART interruption studies.

Distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric HIV infection.

Our understanding of HIV-associated gut microbial dysbiosis in children perinatally-infected with HIV (CLWH) lags behind that of adults living with HIV. Childhood represents a critical window for the gut microbiota. Any disturbances, including prolonged exposure to HIV, antiretroviral drugs, and antibiotics are likely to have a significant impact on long-term health, resulting in a less resilient gut microbiome. The objective of our study was to characterize the gut microbiota in CLWH, and compare it with HIV-unexposed and -uninfected children. We enrolled 31 children aged 3 to 15 years; 15 were CLWH and 16 were HUU. We assessed dietary patterns and quality; quantified soluble and cellular markers of HIV disease progression by flow cytometry, enzyme-linked immunosorbent and multiplex-bead assays, and profiled the gut microbiota by 16S rRNA sequencing. We explored relationships between the gut microbiota, antibiotic exposure, dietary habits, soluble and cellular markers and host metadata. Children had a Western-type diet, their median health eating index score was 67.06 (interquartile range 58.76-74.66). We found no discernable impact of HIV on the gut microbiota. Alpha diversity metrics did not differ between CLWH and HUU. Sex impacted the gut microbiota (R-squared= 0.052, PERMANOVA p=0.024). Male children had higher microbial richness compared with female children. Two taxa were found to discriminate female from male children independently from HIV status: Firmicutes for males, and Bacteroides for females. Markers of HIV disease progression were comparable between CLWH and HUU, except for the frequency of exhausted CD4+ T cells (PD-1+) which was increased in CLWH (p=0.0024 after adjusting for confounders). Both the frequency of exhausted CD4+ and activated CD4+ T cells (CD38+ HLADR+) correlated positively with the relative abundance of Proteobacteria (rho=0.568. false discovery rate (FDR)-adjusted p= 0.029, and rho=0.62, FDR-adjusted p=0.0126, respectively). The gut microbiota of CLWH appears similar to that of HUU, and most markers of HIV disease progression are normalized with long-term ART, suggesting a beneficial effect of the latter on the gut microbial ecology. The relationship between exhausted and activated CD4+ T cells and Proteobacteria suggests a connection between the gut microbiome, and premature aging in CLWH.

Prospective pilot study on the relationship between seminal HIV-1 shedding and genital schistosomiasis in men receiving antiretroviral therapy along Lake Malawi

Male genital schistosomiasis (MGS) is hypothesized to increase seminal shedding of HIV-1. This prospective pilot study assessed seminal HIV-1 RNA shedding in men on long-term ART with and without a diagnosis of MGS. Study visits occurred at 0, 1, 3, 6 and 12 months. MGS was diagnosed by egg positivity on semen microscopy or PCR of seminal sediment. After optimization of the HIV-RNA assay, we examined 72 paired plasma and semen samples collected from 31 men (15 with and 16 without MGS) over 12 months. HIV-1 RNA was detected in 7/72 (9.7%) seminal samples and 25/72 (34.7%) plasma samples. When comparing sample pairs, 5/72 (6.9%) showed HIV-1 RNA detection only in the seminal sample. Overall, 3/31 (9.7%) participants, all with MGS, had detectable HIV-1 RNA in semen while plasma HIV-1 RNA was undetectable (< 22 copies/mL), with seminal levels ranging up to 400 copies/mL. Two participants showing HIV-1 RNA in seminal fluid from the MGS-negative group also had concomitant HIV-1 RNA detection in plasma. The findings suggest that MGS can be associated with low-level HIV-1 RNA shedding despite virologically suppressive ART. Further studies are warranted to confirm these observations and assess its implications.

Impact of obefazimod on viral persistence, inflammation, and immune activation in people with HIV on suppressive antiretroviral therapy.

Persistence of viral reservoirs has been observed in people with HIV (PWH), despite long-term ART, and likely contributes to chronic immune activation and inflammation. Obefazimod is a novel drug that inhibits HIV-1 replication and reduces inflammation. Here we assess whether obefazimod is safe and might impact HIV-1 persistence, chronic immune activation, and inflammation in ART-suppressed PWH. We evaluated obefazimod-related adverse events, changes in cell-associated HIV-1 DNA and RNA, residual viraemia, immunophenotype, and inflammation biomarkers in blood and rectal tissue. We compared 24 ART-suppressed PWH who received daily doses of 50 mg of obefazimod for 12wks (n = 13), or 150 mg for 4wks (n = 11) and 12 HIV-negative individuals who received 50 mg for 4wks. 50 or 150 mg doses of obefazimod were safe, although 150 mg dose showed inferior tolerability. 150 mg dose reduced HIV-1 DNA (p = 0.008, median fold-change = 0.6), and residual viraemia in all individuals with detectable viraemia at baseline. Furthermore, obefazimod upregulated miR-124 in all participants, reduced the activation markers CD38, HLA-DR, and PD-1, and several inflammation biomarkers. The effect of obefazimod by reducing chronic immune activation and inflammation suggests a potential role for the drug in virus remission strategies involving other compounds that can activate immune cells, such as latency-reversing agents.

Quantitative Ultrasound Examination (QUS) of the Calcaneus in Long-Term Martial Arts Training on the Example of Long-Time Practitioners of Okinawa Kobudo/Karate Shorin-Ryu.

Quantitative research of bone tissue related to physical activity (PA) and sport has a preventive dimension. Increasing the parameters of bone tissue strength, especially reaching the maximum value of peak bone strength in childhood, adolescence, and early adulthood due to practicing sports can contribute to maintaining bone health throughout life. Practicing martial arts (tai chi, traditional karate, judo, and boxing) can effectively improve the quality of bone and reduce the risk of falls and fractures. The study aimed to evaluate the calcaneus bones among Okinawa Kobudo/Karate Shorin-Ryu practitioners using the quantitative ultrasound method as an indicator for assessing bone fracture risk. Forty-four adult martial arts practitioners with a mean age of 36.4 participated in this study. Quantitative ultrasound (QUS) with a portable Bone Ultrasonometer was used in this study. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and the stiffness index (SI) were measured. Subjects were assigned to two groups of black and color belts, according to the advancement in Kobudo/karate practice. The measurements of the SI, BUA, SOS, T-score, and Z-score were significantly higher in subjects from the advanced, long-term practice (black belts) (p < 0.05). The long-term martial arts training in traditional karate and Kobudo significantly impacts the parameters of the calcaneus quantitative ultrasound measurements. Significantly higher bone density was observed among the black belt holders. Long-term practice subjects achieved results far beyond the norm for their age groups. Further studies using non-invasive methods of bone quantification are needed to determine the specific conditions for preventing osteoporosis through physical activity, sports, and martial arts, particularly the duration of the activity, the magnitude of loads, and other related factors.

The impact of zygote vitrification timing on pregnancy rate in frozen-thawed IVF/ICSI cycles.

Introduction: Cryopreservation of bipronuclear (2PN) stage zygotes is an integral part of IVF laboratory practice in countries with strict embryo culture legislation. Vitrification of zygotes is compatible with several strategies in infertility treatments holding a freeze-all indication and allows for effective workload management in settings with limited resources. Although it yields high survival rates and clinical outcomes, the ideal timing to commence vitrification of zygotes is elusive while it is empirically practiced in the window between 17 and 21h post-insemination (hpi). We aimed to deduce the association between pregnancy rate and the time interval from insemination (IVF and ICSI) to vitrification to contribute to the standardization ofzygote cryopreservation. Methods: A retrospective analysis of data on vitrification timings and pregnancy outcomes collected between 2011 and 2019 was performed. All included women received an embryo transfer after warming of vitrified zygotes at the 2PN stage. Results: A total of 468 embryo transfers were included of which 182 (38.9%) resulted in pregnancy and 286 (61.1%) not. Vitrification was on average performed 18.74 ±0.63 hpi in the pregnant group and 18.62 ± 0.64 hpi in the non-pregnant group (OR 1.36, 95% CI 1.01; 1.83, p = 0.045). A multivariate analysis controlling for uterine pathologies, maternal age, AMH, the number of MII oocytes, previous history of pregnancy success, endometriosis, AFC, nicotine intake and male factor infertility showed no predictive value of vitrification timing on pregnancy rate. Three time intervals between insemination and vitrification were defined: 17:00 to 18:00 hpi (Group A), 18:01 to 19:00 hpi (Group B) and 19:01 to 21:00 hpi (Group C). Pregnancy occurred in 40/130 women (30.80%) in Group A, in 115/281 women (40.90%) in Group B and in 27/57 women (47.40%) in Group C. Univariate but not multivariate analysis showed a significantly higher pregnancy rate after the latest time interval between insemination and 2PN vitrification when compared to the earliest (Group C vs. A, OR 2.03, 95% CI 1.07; 3.84, p = 0.031). Discussion: These findings encourage further investigation on the impact of vitrification timing on clinical outcomes and hold the potential to standardize cryopreservation of zygotes from IVF/ICSI cycles to eventually improve the quality of long-term ART outcomes.

또래 중심 생태 미술 활동이 지적장애 학생의 공격성 완화에 미치는 효과

Objectives Purpose The purpose of this study is to investigate the effect of peer-centered ecological art activities on alleviating aggression of students with intellectual disabilities.&#x0D; Methods To this end, it was pointed out that among the students in the third grade of middle school requested by the homeroom teacher, they received a score of 21 or higher on the aggression scale of the shortened Conner rating scale, as they were having difficulties adjusting to school life due to their aggressive attitude among the classes of H special school located in Busan. Four students with disabilities (1 male, 3 female) were selected as the research subjects.&#x0D; Results TLooking at the results, it was found that before the peer-centered ecological art program was implemented, all five areas of the adaptive behavior test standardized test (K-ABS) aggression decreased after the peer-centered ecological art program was implemented. Among the sub-items, ‘61. The most significant decrease was in the category of 'I am violent or angry.’ In addition, looking at the observation log of the peer-centered ecological art program, as the sessions progressed during the program, the students' attitudes toward natural subjects and materials and their finished works became more serious and calm, and their aggressive behavior decreased. It was found that there was also a positive change in the action.&#x0D; Conclusions In conclusion, it was found that the aggression of students with intellectual disabilities was reduced through the development and application of a peer-centered ecological art program. Recognizing that many students with intellectual disabilities have this problem of maladaptive behavior in the future, if a more systematic and long-term peer-centered ecological art program is developed, it will be of more help in reducing the aggression of students with intellectual disabilities, and continuous research is required.

Safety and Tolerability of Oral Cannabinoids in People Living with HIV on Long-Term ART: A Randomized, Open-Label, Interventional Pilot Clinical Trial (CTNPT 028).

With anti-inflammatory properties, cannabinoids may be a potential strategy to reduce immune activation in people living with HIV (PLWH) but more information on their safety and tolerability is needed. We conducted an open-label interventional pilot study at the McGill University Health Centre in Montreal, Canada. PLWH were randomized to oral Δ9-tetrahydrocannabinol (THC): cannabidiol (CBD) combination (THC 2.5 mg/CBD 2.5 mg) or CBD-only capsules (CBD 200 mg). Individuals titrated doses as tolerated to a maximum daily dose THC 15 mg/CBD 15 mg or 800 mg CBD, respectively, for 12 weeks. The primary outcome was the percentage of participants without any significant toxicity based on the WHO toxicity scale (Grades 0-2 scores). Out of ten individuals, eight completed the study. Two from the CBD-only arm were withdrawn for safety concerns: phlebotomy aggravating pre-existing anemia and severe hepatitis on 800 mg CBD with newly discovered pancreatic adenocarcinoma, respectively. Seven did not have any significant toxicity. Cannabinoids did not alter hematology/biochemistry profiles. CD4 count, CD4/CD8 ratio, and HIV suppression remained stable. Most adverse effects were mild-moderate. In PLWH, cannabinoids seem generally safe and well-tolerated, though larger studies are needed. Screening for occult liver pathology should be performed and hepatic enzymes monitored, especially with high CBD doses.

PP 3.6 – 00122 Heterogeneous associations between HIV genomic integrity and proviral longevity during long-term ART

PP 3.6 – 00122 Heterogeneous associations between HIV genomic integrity and proviral longevity during long-term ART

OP 4.7 – 00121 Circulating immune predictors of intact HIV reservoir decay during long-term ART

OP 4.7 – 00121 Circulating immune predictors of intact HIV reservoir decay during long-term ART

P 4.2 – 00029 Innate Immune Correlates of Cell-Associated HIV RNA And DNA During Long-Term Suppressive ART

P 4.2 – 00029 Innate Immune Correlates of Cell-Associated HIV RNA And DNA During Long-Term Suppressive ART

Art Therapy as a Complementary Treatment to Address Psychosocial Wellbeing of Aphasia Patients

Aphasia is an acquired neurological disorder resulting from traumatic brain injuries that affect patients’ ability to process various aspects of language. Aphasia patients most notably have difficulty communicating effectively and expressing their thoughts verbally. Because aphasia is a language processing disorder, it does not affect a patient’s intelligence, hearing, or muscle activity. Due to the sudden inability to perform previously attainable tasks, this disorder may drastically affect the mental health of a patient. Currently, aphasia patients are merely directed to traditional speech and language therapy, as speech and language therapists aim to improve aphasia patients’ muscle movements and ultimately help recover their ability to speak. Seeking mental health care may be restrictive due to costs and difficulty navigating the system. &#x0D; While art therapy has been a subject of interest in aiding the treatment of patients with neurological disorders in general, it has not yet been fully explored in the context of aphasia treatments, which prioritize the exercise of motor skills. Though there have been recent studies showing art therapy’s promise in improving mental health, there is a lack of interest in implementing methods other than speech and language therapy. My paper emphasizes the importance of mental health in aphasia patients, establishes the benefits of art therapy, and proposes long-term art therapy programs that are accessible and informative to be complemented with speech and language therapies at medical offices and aphasia centers. Future research should assess the effectiveness of speech and language therapy in concert with complementary art therapy.

CYP3A and CYP2B6 Genotype Predicts Glucose Metabolism Disorder among HIV Patients on Long-Term Efavirenz-Based ART: A Case-Control Study.

Long-term antiretroviral treatment (cART) increases the risk of glucose metabolism disorders (GMDs). Genetic variation in drug-metabolizing enzymes and transporters may influence susceptibility to cART-associated GMDs. We conducted a case-control study to investigate the association of pharmacogenetic variations with cART-induced GMDs. A total of 240 HIV patients on long-term efavirenz-based cART (75 GMD cases and 165 controls without GMDs) were genotyped for CYP3A4*1B, CYP3A5 (*3,*6), CYP2B6*6, UGT2B7*2, ABCB1 (c.3435C>T, c.4036A>G), and SLCO1B1 (*1b, *5). GMD cases were defined as the presence of impaired fasting glucose, insulin resistance, or diabetes mellitus (DM). Case-control genotype/haplotype association and logistic regression analysis were performed by adjusting for age, sex, and BMI. The major CYP3A haplotype were CYP3A5*3 (53.8%), CYP3A4*1B (17.3%), combinations of CYP3A4*1B, and CYP3A5*6 (10.9%), and CYP3A wild type (7%). CYP3A5*6 allele (p = 0.005) and CYP3A5*6 genotype (p = 0.01) were significantly associated with GMD cases. Multivariate analysis indicated CYP3A haplotype as a significant predictor of GMD (p = 0.02) and IFG (p = 0.004). CYP2B6*6 significantly predicted DM (p = 0.03). CYP3A haplotype and CYP2B6*6 genotype are independent significant predictors of GMD and DM, respectively, among HIV patients on long-term EFV-based cART.