Re-evaluating the relationship between youth with HIV and BMI in an age of increasing rates of overweight and obese youth.

BACKGROUND: Newer antiretrivirals (ART) have shifted the metabolic experiences of people with HIV (PWH) from those of wasting syndrome to increases in body mass index (BMI). This study sought to examine the relationship between BMI and ART use among youth with HIV (YWH). METHODS: Charts from YWH ages 10-24 with at least two documented BMIs at least 6 months apart between 2017 and 2020 were included (N = 44). Statistical analyses were conducted in SAS 9.4. RESULTS: Clients were predominately African American (66%) males (73%) aged 19-24 years (64%), with men having sex with men (48%) being the most common mode of transmission. YWH on non-integrase inhibitor (INSTI) regimens had greater absolute increases in BMI compared to those on INSTI regimens (p = 0.03). Fourteen percent of clients using INSTI experienced an increase in BMI class from normal to overweight or overweight to obese; no non-INSTI users changed BMI class. Time since diagnosis and BMI change due to weight gain were positively associated (p = 0.03) among behaviorally-acquired YWH. CONCLUSIONS: Increasing BMI and changing BMI classes may be more likely among YWH using INSTI. More longitudinal studies inclusive of diet and exercise profiles are needed to understand the relationship between INSTI and YWH BMI.

Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review.

BACKGROUND: Dolutegravir (DTG) is a cornerstone of global antiretroviral (ARV) therapy (ART) due to its high efficacy and favorable tolerability. However, limited data exist regarding the risk of emergent integrase strand transfer inhibitor (INSTI) drug-resistance mutations (DRMs) in individuals receiving DTG-containing ART. METHODS: We performed a PubMed search using the term "Dolutegravir", last updated 18 December 2023, to estimate the prevalence of VF with emergent INSTI DRMs in people living with HIV (PLWH) without previous VF on an INSTI who received DTG-containing ART. RESULTS: Of 2131 retrieved records, 43 clinical trials, 39 cohorts, and 6 cross-sectional studies provided data across 6 clinical scenarios based on ART history, virological status, and co-administered ARVs: (1) ART-naïve PLWH receiving DTG plus two NRTIs; (2) ART-naïve PLWH receiving DTG plus lamivudine; (3) ART-experienced PLWH with VF on a previous regimen receiving DTG plus two NRTIs; (4) ART-experienced PLWH with virological suppression receiving DTG plus two NRTIs; (5) ART-experienced PLWH with virological suppression receiving DTG and a second ARV; and (6) ART-experienced PLWH with virological suppression receiving DTG monotherapy. The median proportion of PLWH in clinical trials with emergent INSTI DRMs was 1.5% for scenario 3 and 3.4% for scenario 6. In the remaining four trial scenarios, VF prevalence with emergent INSTI DRMs was ≤0.1%. Data from cohort studies minimally influenced prevalence estimates from clinical trials, whereas cross-sectional studies yielded prevalence data lacking denominator details. CONCLUSIONS: In clinical trials, the prevalence of VF with emergent INSTI DRMs in PLWH receiving DTG-containing regimens has been low. Novel approaches are required to assess VF prevalence with emergent INSTI DRMs in PLWH receiving DTG in real-world settings.

Temporary increase in circulating replication-competent latent HIV-infected resting CD4+ T cells after switch to an integrase inhibitor based antiretroviral regimen.

BACKGROUND: The principal barrier to an HIV cure is the presence of the latent viral reservoir (LVR), which has been understudied in African populations. From 2018 to 2019, Uganda instituted a nationwide rollout of ART consisting of Dolutegravir (DTG) with two NRTI, which replaced the previous regimen of one NNRTI and the same two NRTI. METHODS: Changes in the inducible replication-competent LVR (RC-LVR) of ART-suppressed Ugandans with HIV (n = 88) from 2015 to 2020 were examined using the quantitative viral outgrowth assay. Outgrowth viruses were examined for viral evolution. Changes in the RC-LVR were analyzed using three versions of a Bayesian model that estimated the decay rate over time as a single, linear rate (model A), or allowing for a change at time of DTG initiation (model B&C). FINDINGS: Model A estimated the slope of RC-LVR change as a non-significant positive increase, which was due to a temporary spike in the RC-LVR that occurred 0-12 months post-DTG initiation (p < 0.005). This was confirmed with models B and C; for instance, model B estimated a significant decay pre-DTG initiation with a half-life of 6.9 years, and an ∼1.7-fold increase in the size of the RC-LVR post-DTG initiation. There was no evidence of viral failure or consistent evolution in the cohort. INTERPRETATION: These data suggest that the change from NNRTI- to DTG-based ART is associated with a significant temporary increase in the circulating RC-LVR. FUNDING: Supported by the NIH (grant 1-UM1AI164565); Gilead HIV Cure Grants Program (90072171); Canadian Institutes of Health Research (PJT-155990); and Ontario Genomics-Canadian Statistical Sciences Institute.

Resistencia a los inhibidores de la integrasa en niños con el virus de la inmunodeficiencia humana por transmisión vertical: primeros casos en Uruguay / Resistance to integrase inhibitors in children with vertically-transmitted human immunodeficiency virus: First cases in Uruguay

La resistencia a los antirretrovirales (ARV) es un problema de salud pública. Con el uso de inhibidores de la integrasa (INSTI) en pediatría, también comienzan a aparecer resistencias. El objetivo de esta comunicación es describir 3 casos con resistencia a los INSTI. Se describen 3 pacientes pediátricos con transmisión vertical del virus de la inmunodeficiencia humana (VIH). Iniciaron ARV de lactantes y preescolares, con mala adherencia al tratamiento, cursaron con diferentes planes secundarios a comorbilidades asociadas y fallas virológicas por resistencia. Los 3 casos clínicos describen la rápida aparición de resistencia frente a la falla virológica y el compromiso de los INSTI. La adherencia debe ser supervisada para detectar precozmente el aumento de la viremia. La falla virológica en un paciente tratado con raltegravir obliga a un rápido cambio de esquema ARV, ya que continuar utilizándolo podría favorecer nuevas mutaciones y resistencia a los INSTI de segunda generación.

Antiretroviral (ARV) drug resistance is a public health issue. Resistance has also been observed in the case of integrase strand transfer inhibitors (INSTIs) used in pediatrics. The objective of this article is to describe 3 cases of INSTI resistance. These are the cases of 3 children with vertically-transmitted human immunodeficiency virus (HIV). They were started on ARVs as infants and preschoolers, with poor treatment adherence, and had different management plans due to associated comorbidities and virological failure due to resistance. In the 3 cases, resistance developed rapidly as a result of virological failure and INSTI involvement. Treatment adherence should be monitored so that any increase in viremia can be detected early. Virological failure in a patient treated with raltegravir forces to a rapid change in ARV therapy because its continued use may favor new mutations and resistance to second-generation INSTIs.

The effect of a treatment switch to integrase Strand transfer inhibitor-based regimens on weight gain and other metabolic syndrome-related conditions.

OBJECTIVE: This study aimed to assess weight gain associated with treatment switching to INSTI-based regimens in people living with HIV (PLWH) and to determine whether it is accompanied by worsening features of hypertension, dyslipidemia, or hyperglycemia. METHODS: In this two-center retrospective observational study, we assessed weight gain and metabolic features in PLWH who switched to an INSTI-based regimen (study group) as compared to patients who remained on a non-INSTI regimen (control group) over a 24-month follow-up period. RESULTS: One-hundred seventy-four PLWH were included in the study group, and 175 were included in the control group. The study group gained 2.51 kg ± 0.31 (mean ± standard deviation) over the 2 years of follow-up, while the control group gained 1.1 ± 0.31 kg over the same time course (p < 0.001). INSTI treatment, Caucasian origin, and lower BMI were risk factors associated with excessive weight gain during the 2 years of follow-up. Among metabolic parameters, only glucose levels increased after initiating INSTI-based regimens, although limited to males of African origin (p = 0.009). CONCLUSIONS: We observed a mild weight gain after switching to INSTI-based regimens, with no major impact on metabolic parameters over 2 years of follow-up. Longer follow-up might be needed to observe the adverse metabolic effects of INSTI-based regimens. The impact on weight gain should be discussed with every patient before the treatment switch to ensure a balanced diet and physical activity to prevent excessive weight gain that might hamper compliance with ART.

Portable Nanopore sequencing solution for next-generation HIV drug resistance testing.

BACKGROUND: Tackling HIV drug resistance is one of major challenges for ending AIDS epidemic, but the elevated expense of cutting-edge genomics hampers the advancement of HIV genotype testing for clinical care. METHODS: We developed a HIV genotype testing pipeline that centers on a cost-efficient portable Nanopore sequencer. Accuracy verification was conducted through comparison with parallel data obtained via fixed-site Pacbio sequencing. Our complete pol-gene sequencing strategy coupled with portable high-throughput sequencing was applied to identify drug resistance mutations across 58 samples sourced from the ART-treated Los Angeles General Medical Center Rand Schrader Clinic (LARSC) cohort (7 samples from 7 individuals) and the ART-naïve Center for HIV/AIDS Vaccine Immunology (CHAVI) cohort (51 samples from 38 individuals). RESULTS: A total of 472 HIV consensus sequences, each tagged with a unique molecular identifier, were produced from over 1.4 million bases acquired through portable Nanopore sequencing, which matched those obtained independently via Pacbio sequencing. With this desirable accuracy, we first documented the linkage of multidrug cross-resistance mutations across Integrase Strand Transfer inhibitors (INSTIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from an individual failing a second-generation INSTI regimen. By producing more than 500 full-length HIV pol gene sequences in a single portable sequencing run, we detected Protease Inhibitor (PI), Nucleoside Reverse Transcriptase Inhibitor (NRTI), NNRTI and INSTI resistance mutations. All drug resistance mutations identified through portable sequencing were cross-validated using fixed-site Pacbio sequencing. CONCLUSIONS: Our accurate and affordable HIV drug resistance testing solution is adaptable for both individual patient care and large-scale surveillance initiatives.

Resistance to integrase inhibitors in children with vertically-transmitted human immunodeficiency virus: First cases in Uruguay. / Resistencia a los inhibidores de la integrasa en niños con el virus de la inmunodeficiencia humana por transmisión vertical: primeros casos en Uruguay.

Antiretroviral (ARV) drug resistance is a public health issue. Resistance has also been observed in the case of integrase strand transfer inhibitors (INSTIs) used in pediatrics. The objective of this article is to describe 3 cases of INSTI resistance. These are the cases of 3 children with vertically-transmitted human immunodeficiency virus (HIV). They were started on ARVs as infants and preschoolers, with poor treatment adherence, and had different management plans due to associated comorbidities and virological failure due to resistance. In the 3 cases, resistance developed rapidly as a result of virological failure and INSTI involvement. Treatment adherence should be monitored so that any increase in viremia can be detected early. Virological failure in a patient treated with raltegravir forces to a rapid change in ARV therapy because its continued use may favor new mutations and resistance to second-generation INSTIs.

La resistencia a los antirretrovirales (ARV) es un problema de salud pública. Con el uso de inhibidores de la integrasa (INSTI) en pediatría, también comienzan a aparecer resistencias. El objetivo de esta comunicación es describir 3 casos con resistencia a los INSTI. Se describen 3 pacientes pediátricos con transmisión vertical del virus de la inmunodeficiencia humana (VIH). Iniciaron ARV de lactantes y preescolares, con mala adherencia al tratamiento, cursaron con diferentes planes secundarios a comorbilidades asociadas y fallas virológicas por resistencia. Los 3 casos clínicos describen la rápida aparición de resistencia frente a la falla virológica y el compromiso de los INSTI. La adherencia debe ser supervisada para detectar precozmente el aumento de la viremia. La falla virológica en un paciente tratado con raltegravir obliga a un rápido cambio de esquema ARV, ya que continuar utilizándolo podría favorecer nuevas mutaciones y resistencia a los INSTI de segunda generación.

Pharmacogenetics of weight gain following switch from efavirenz- to integrase inhibitor-containing regimens.

BACKGROUND: Excessive weight gain affects some persons with HIV after switching to integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART). We studied associations between CYP2B6 genotype and weight gain after ART switch among ACTG A5001 and A5322 participants. METHODS: Eligible participants switched from efavirenz- to INSTI-containing ART, had genotype data, and had weight data at least once from 4 weeks to 2 years post-switch. Multivariable linear mixed effects models adjusted for race/ethnicity, CD4, age, BMI and INSTI type assessed relationships between CYP2B6 genotype and estimated differences in weight change. RESULTS: A total of 159 eligible participants switched ART from 2007 to 2019, of whom 138 had plasma HIV-1 RNA < 200 copies/mL (65 CYP2B6 normal, 56 intermediate, 17 poor metabolizers). Among participants with switch HIV-1 RNA < 200 copies/mL, weight increased in all 3 CYP2B6 groups. The rate of weight gain was greater in CYP2B6 poor than in CYP2B6 normal metabolizers overall, and within 9 subgroups (male, female, White, Black, Hispanic, dolutegravir, elvitegravir, raltegravir, and TDF in the pre-switch regimen); only in Hispanic and elvitegravir subgroups were these associations statistically significant ( P  < 0.05). Compared to normal metabolizers, CYP2B6 intermediate status was not consistently associated with weight gain. CONCLUSION: CYP2B6 poor metabolizer genotype was associated with greater weight gain after switch from efavirenz- to INSTI-containing ART, but results were inconsistent. Weight gain in this setting is likely complex and multifactorial.

Energy balance and body composition after switch between integrase strand transfer inhibitors and doravirine among people with HIV.

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are associated with excessive weight gain among a subset of persons with HIV (PWH), due to unclear mechanisms. We assessed energy intake (EI) and expenditure (EE) following switch off and onto INSTIs. METHODS: PWH with >10% weight gain on an INSTI-based regimen switched INSTI to doravirine for 12 weeks, then back to INSTI for 12 weeks while keeping their remaining regimen stable. Twenty-four-hour EE, EI and weight were measured on INSTI, following switch to doravirine, and upon INSTI restart. Mixed models analysed changes over time. RESULTS: Among 18 participants, unadjusted 24 h EE decreased by 83 (95% CI -181 to 14) kcal following switch to doravirine, and by 2 (-105 to 100) kcal after INSTI restart; energy balance (EE-EI) increased by 266 (-126 to 658) kcal from Week 0 to Week 12, and decreased by 3 (-429 to 423) kcal from Week 12 to Week 24. Trends toward weight loss occurred following switch to doravirine [mean -1.25 (-3.18 to 0.69) kg] and when back on INSTI [-0.47 (-2.45 to 1.52) kg]. Trunk fat decreased on doravirine [-474 (-1398 to 449) g], with some regain following INSTI restart [199 (-747 to 1145) g]. Fat-free mass decreased on doravirine [-491 (-1399 to 417) g] and increased slightly after INSTI restart [178 (-753 to 1108) g]. CONCLUSIONS: Among PWH with >10% weight gain on an INSTI, switch to doravirine was associated with a trend towards decreases in 24 h EE, weight, trunk fat mass and fat-free mass. Observed changes were not significant, but suggest a mild weight-suppressive effect of doravirine among PWH.

Clinical significance and management of low-level HIV viremia in the era of integrase strand transfer inhibitors.

BACKGROUND: People living with HIV (PLWH) and receiving antiretroviral therapy (ART) have a goal of achieving and maintaining viral suppression; however, the existence of PLWH that show events of low-level viremia (LLV) between 50 and 1000 copies/mL and with different virological consequences have been observed. Moreover, some reports indicate that LLV status can lead to residual immune activation and inflammation, leading to a higher occurrence of non-AIDS-defining events (nADEs) and other adverse clinical outcomes. Until now, however, published data have shown controversial results that hinder understanding of this phenomenon's actual cause(s) and origin(s). Integrase strand transfer inhibitors (INSTIs)-based therapies could lead to lower LLV over time and, therefore, more effective virological control. OBJECTIVES: This review aims to assess recent findings to provide a view of the clinical significance and management of low-level HIV viremia in the era of INSTIs.

Effect of dolutegravir-based drug combinations on the level of medication adherence and viral load among adolescents living with HIV in resource-limited setting: a pre-post design.

OBJECTIVES: The use of antiretroviral drugs among HIV-infected adolescents has been challenged with poor medication adherence, leading to an unsuppressed viral load and ultimately to drug resistance. Recently, dolutegravir has been approved for use in adolescents with HIV, but the evidence on medication adherence and viral load suppression is limited. The study determined the effect of dolutegravir-based drug regimens on the level of medication adherence and viral load among treatment-experienced adolescents. METHODS: A longitudinal pre-post design study was done among adolescents living with HIV at a paediatrics clinic in Nigeria. Assessment of medication adherence and viral load testing was done before and at six months of transitioning to dolutegravir-based regimens. McNemar-chi-square was used to determine the effectiveness of the drug on adherence and viral load suppression. Multivariate logistic regression analysis was performed to determine the predictors of drug adherence and viral suppression. RESULTS: The mean age of the participants was 14.7 years (SD=3.2), and 53.3 % were males. The mean duration of ART use was 10.3 years (SD=3.2). Six months after transitioning to dolutegravir, there was a significant decrease in viral load (Z=-7.947, p<0.001) and an increase in medication adherence score (Z=-7.554, p<0.001), among the treatment-experienced adolescents. Viral suppression was 13 times higher among respondents with good medication adherence as compared to those with poor medication adherence (AOR=13.24, CI=3.25-53.90). CONCLUSIONS: Dolutegravir is effective in improving medication adherence and viral suppression among Adolescents living with HIV. Thus, the need to transition eligible adolescents to dolutegravir to sustain better treatment outcomes.

Dolutegravir-induced growth and lifespan effects in Caenorhabditis elegans.

BACKGROUND: Integrase strand transfer inhibitor (INSTIs)-based combination antiretroviral treatment in people living with HIV (PLWH) has been reportedly correlated with several adverse effects, such as weight gain, fetal defects or psychiatric disorders. METHODS: To comprehensively understand the adverse effect of INSTIs, our study utilized Caenorhabditis Elegans (C. elegans) as a model to investigate how dolutegravir (DTG) affected its life cycle, growth, reproduction and lifespan. RESULTS: Our results indicated that DTG enhanced body growth at the early stage of treatment, but no change was detected for long-term treatment. The treatment also influenced the reproductive system, decreased egg-hatching but had no effect on egg-laying. Besides, DTG resulted in lifespan reduction, which is dependent on increased levels of reactive oxidative species (ROS) accumulation. Treatment with N-acetyl-cysteine (NAC) in worms restrained intracellular ROS accumulation and improved DTG-induced lifespan reduction. CONCLUSIONS: Our study demonstrates for the first time the effect of DTG treatment on life cycle. DTG-induced adverse effects are potentially associated with intracellular ROS accumulation. Quenching ROS accumulation might provide a novel strategy for dealing with the adverse effects of INSTIs.

A Comprehensive Literature Review of Treatment-Emergent Integrase Resistance with Dolutegravir-Based Regimens in Real-World Settings.

After a decade of dolutegravir (DTG) use in various antiretroviral therapy combinations and in diverse populations globally, it is critical to identify HIV strains with reduced drug susceptibility and monitor emergent resistance in people living with HIV who experience virologic failure while on DTG-based regimens. We searched the PubMed, Embase, and Cochrane databases to identify studies that reported DTG resistance-associated mutations (RAMs) emerging under selection pressure. Our review showed that RAMs conferring resistance to DTG were rare in 2-drug and 3-drug regimens used in real-world cohorts, corroborating data from clinical trials. The potency of DTG in maintaining virologic suppression was demonstrated, even in cases of pre-existing resistance to companion drugs in the regimen. Estimates of DTG RAMs depended on the population and certain risk factors, including monotherapy, baseline resistance or lack of genotypic testing, treatment history and prior virologic failure, and suboptimal treatment adherence. The RAMs detected after virologic failure, often in heavily treatment-experienced individuals with prior exposure to integrase strand transfer inhibitors, were G118R, E138K, G140A/C/R/S, Q148H/K/R, N155H, and R263K. Overall, these data highlight the durable effectiveness and high barrier to resistance of DTG as part of combination antiretroviral therapy in a wide variety of settings.

Prevalence and analysis of acquired and transmitted integrase strand transfer inhibitor-associated HIV-1 drug resistance in Chongqing, China.

In this study, we examined the occurrence of acquired and transmitted drug resistance to integrase strand transfer inhibitor (INSTI) in HIV-1 strains in Chongqing (China) for guiding for the routine testing of INSTI-associated HIV-1 genotype resistance. Plasma samples were obtained from HIV-1 patients at Chongqing Public Health Medical Center from July 2019 to August 2022. Besides, amplification, sequence, and analysis of the portion of the HIV-1 pol gene that encodes the integrase protein were implemented to identify INSTI resistance. Integrase sequence data was harvested for a comprehensive cohort of 1032 patients infected with HIV-1. This cohort consisted of 564 ART-naive patients, 465 ART-treated patients, and 3 patients with an unknown treatment history. Within the study group, we identified INSTI resistance in 21 patients (2.03%, 21/1032), including 17 ART-treated patients (3.66%, 17/465). Among the ART-treated patients, 12 were INSTI-treated (11.76%, 12/102), 5 were INSTI-naive (1.38%, 5/363), and 4 were ART-ineffective patients (0.71%, 4/564). The prevalent major resistance mutation was Q148R (0.48%, 5/1032), while the most prevalent accessory resistance mutation was E157Q (1.65%, 17/1032). In light of the above, it is recommended that the incidence of accessory genotype analysis should be considered before starting any future INSTI-based therapy, especially in patients with drug resistance to NRTIs and NNRTIs and the reduction of INSTI sensitivity should be carefully monitored and investigated. Regular monitoring for resistance should be implemented after the use of INSTIs, and, importantly, ongoing monitoring of the decreasing susceptibility to INSTIs is crucial following the initiation of treatment with INSTIs.

Comparison of Metabolic Effects of Three Different Treatment Combinations with Retrospective Real-life Data in People Living with HIV.

INTRODUCTION: Comorbidities are increasing in people living with HIV (PLHIV), and different treatment options have advantages and disadvantages. It is important to compare information from real-life treated cases. The aim of this study was to retrospectively evaluate the data on efficacy and clinical and laboratory findings during different antiretroviral therapies. METHODS: Retrospective file data of 47 PLHIV using Dolutegravir and Lamivudine (3TC/DTG), Tenofovir Alafenamide Emtricitabine and Elvitegravir Cobicistat (EVG/c/TAF/FTC) and Tenofovir Disoproxil Fumarate and Emtricitabine and Efavirenz (EFV/FTC/TDF) were analyzed. Data of the patients at baseline and 12 months after antiretroviral therapy (ART) were compared. RESULTS: About 47 PLHIV were included in the study. Of the patients, 22 (46.8%) were in the 3TC/DTG group, 19 (40.4%) in the EVG/c/TAF/FTC, and 6 (12.8%) in the EFV/FTC/TDF group. After 12 months of treatment, BMI, HIV-RNA, CD4, WBC, hemoglobin, MCV, PDW, RDW, platelet count, creatinine, eGFR, HDL, AST, glucose values of the 3TC/DTG group were significantly different (p<0.05). After 12 months of treatment, BMI, HIV-RNA, CD4 count, MCV, creatinine, eGFR, HDL, LDL, TG, TC, AST, and HOMA-IR values of the EVG/c/TAF/FTC treatment group were significantly different (p<0.05). After 12 months of treatment, HIV RNA, total bilirubin, and LDL values in the EFV/FTC/TDF treatment group were statistically different (p<0.05). CONCLUSION: All treatment groups showed a decrease in HIV-RNA and an increase in CD4 at the end of one year. While CD4 elevation is lower in EFV recipients than in integrase inhibitor (INSTI) recipients, weight gain is higher in INSTI recipients. While the lipid profile was more positively affected in the 3TC/DTG group, lipid profiles were more negatively affected in the EVG/c/TAF/FTC group, although liver and kidney functions were preserved.

Effect of Dolutegravir regimen against other regimens on some hematological parameters, CD4 count and viral load of people living with HIV infection in South Eastern Nigeria.

BACKGROUND: Appropriate usage of highly active antiretroviral therapy (HAART) suppresses human immunodeficiency virus (HIV) replication. One of such HAART is dolutegravir (DTG) containing regimen which Nigeria included in her national protocol, as the preferred first-line option, with particularly fixed dose combination of tenofovir/lamivudine/dolutegravir (TLD) in 2018. AIM: To access the impact of this regimen as against other regimens on some hematological parameters as well as cluster of differentiation 4 (CD4) count and viral load on people living with HIV infection. METHODS: The study site is a health facility center supported by President Emergency Plan for acquired immunodeficiency syndrome (AIDS) Relief where people living with HIV infection (PLWHIV) visit for their routine management in Abakaliki, Ebonyi State. A hundred and twenty-two (122) subjects participated, 58 PLWHIV and 64 control subjects. CD4 + count by partec cyflow auto analyzer, while the Viral load assay was by Roche COBAS Ampriplep/COBAS TaqMan molecular systems. Full blood count determination was by Sysmex XE-2100 hematology auto analyzer, while the detection of antibody to HAART was by Petz and direct Coombs tests. RESULTS: Mean values of hemoglobin (Hb), Total white cell count, Lymphocytes, Monocytes and CD4 + counts of people living with HIV infection (PLWHIV) were significantly (P = .0001) lower than the control subjects. The Hb level of PLWHIV on Efavirenz combination (TDF/3TC/EFV) are comparable 123 ± 32g/l with those on Ritonavir combination (TDF/3TC/LPV/R) 136 ± 16g/l and Dolutegravir (TLD)134 ± 20.0g/l (P = .307). On the other hand, total white cell count (4.55 ± 1.99 × 109/L) of those on Efavirenz combination (TDF/3TC/EFV) and Dolutegravir (TLD) (4.53 ± 1.31 × 109/L) were significantly higher than those on Ritonavir combination (TDF/3TC/LPV/R) (4.09 ± 1.15 × 109/L). The Viral Load of PLWHIV on Dolutegravir (TLD) was significantly lower 171.57 ± 4.56 copies/mL than those on Efavirenz combination (TDF/3TC/EFV) (86,395.91 ± 27,476.57copies/mL) and Ritonavir combination (TDF/3TC/LPV/R) (81,188.83 ± 13,393.47 copies/mL), respectively. CONCLUSION: Some hematological parameters (such as Hb, total white cell counts and CD4 + count) were lower in people living with HIV than values seen in control group. The 3 regimens used in the management of HIV infection in the locality revealed comparable Packed cell volume and Hemoglobin levels. Total white cell count of those on Efavirenz and DTG is comparable with higher values than those on Ritonavir.

Impact of Integrase Strand Transfer Inhibitors on Cognition in the HAILO Cohort.

BACKGROUND: Integrase inhibitors (INSTIs) have been associated with poorer cognition in people with HIV (PWH). We examined the impact of switching to INSTIs on neuropsychological (NP) outcomes in PWH 40 years of age and older. METHODS: From the AIDS Clinical Trials Group observational cohort study, HAILO, we identified PWH who switched to INSTIs, had ≥2 NP assessments before and at least 1 after switch, and maintained viral suppression while on INSTIs. NP performance was assessed with a composite score (NPZ4) including Hopkins Verbal Learning Test (HVLT-R), Digit Symbol test (DSY), Trail Making A, and Trail Making B, while adjusting for covariates and learning effects. Outcomes changes from preswitch and postswitch periods were estimated using piecewise linear mixed models. RESULTS: Among 395 PWH (mean age 54 years, 81% male, 20% Hispanic, and 29% Black) NPZ4 increased preswitch and postswitch. There was no difference in slopes between periods for NPZ4 [preswitch 0.036/year (95% CI: 0.03 to 0.043); postswitch 0.022/year (95% CI: 0.006 to 0.005); P = 0.147]. All tests scores improved preswitch (P < 0.01). Postswitch, Trail Making A and DSY increased (all P < 0.01) without differences in rate of change (all P > 0.05). HVLT-R had a nonsignificant decrease postswitch (P = 0.22), resulting in a significant preswitch vs postswitch difference in slopes (P = 0.03). CONCLUSIONS: NP performance improved regardless of INSTI use. There was an attenuation of improvement in verbal memory in the postswitch vs preswitch period. The clinical significance of these changes is unclear but, overall, INSTIs did not have a consistent detrimental effect on NP outcomes.

IP-10 and MIG are sensitive markers of early virological response to HIV-1 integrase inhibitors.

Background: Interferon-inducible protein-10 (IP-10) and monokine induced by interferon-gamma (MIG) are chemokines recognized as inflammatory biomarkers during HIV-1 infection. We assessed their early and long-term dynamics after initiation of antiretroviral treatment (ART). Methods: Persons with HIV-1 (PWH) aged>18 years starting their first ART in 2015-2021 in a prospective cohort (n=73) were included. IP-10 and MIG plasma levels were quantified using a multiplexed bead-based assay. Results: IP-10 and MIG plasma levels showed a significant and consistent reduction following ART (80% integrase inhibitor [INSTI]-based) initiation, starting at day 20 and maintained throughout the study period (48 months), paralleling the HIV-1 RNA decay and CD4+ count recovery (p<0·001). At baseline, PWH≥ 50 years, CDC stage C and CD4+ count<350cells/mm3 had higher levels of IP-10 (p=0·022, p=0·001 and p=0·002, respectively) and MIG (p<0·001, p=0·024 and p=0·069, respectively). All of them matched their counterparts several months following ART initiation. MIG levels showed a greater decrease at day 10 in those treated with INSTI (p=0·038). Low-level HIV-1 viremia did not impact MIG or IP-10 levels. Conclusion: Plasma IP-10 and MIG showed an early significant decline following ART initiation, with greater early declines in MIG levels in INSTI-based regimens. These findings suggest a strong impact of HIV-1 viremia on IP-10 and MIG levels.