Case series of two persons living with HIV with detectable viral loads initiated then suppressed on cabotegravir/rilpivirine with lenacapavir.

Long-acting (LA) cabotegravir/rilpivirine (CAB/RPV) is primarily prescribed for virologically suppressed persons living with HIV (PLWH). Patients experiencing pill dysphagia or profound adherence challenges were excluded from the phase 3 studies, but recent reports demonstrate successful treatment in PWLH with baseline viremia. We describe two PLWH with detectable viral loads (VL) with multidrug resistance mutations. They were unable to sustain virologic suppression on oral therapy with historical poor adherence and dysphagia. Initiation of intramuscular CAB/RPV with subcutaneous lenacapavir (LEN) injections was necessary with baseline resistance. Due to anorexia and a low muscle mass, one patient received CAB/RPV injections in the vastus lateralis rather than the gluteal muscle with a 67-day delay between injections three and four due to health challenges. Both achieved viral suppression on monthly CAB/RPV with LEN. A return to health with a BMI increase from <14 kg/m2 to almost 17 kg/m2 resulted in the second patient. Injectable LA ART (CAB/RPV + LEN) in PLWH with detectable viremia results in sustained virologic suppression and a return to health and should now be considered a novel option for MDR patients with an inability to adhere to oral regimens.

Differential T-cell profiles determined by Hepatitis B surface antigen decrease among people with Human Immunodeficiency Virus /Hepatitis B Virus coinfection on treatment.

BACKGROUND: Several studies have reported that combination antiretroviral therapy (cART) enhances the hepatitis B surface antigen (HBsAg) clearance rate in Human Immunodeficiency Virus-1/Hepatitis B Virus (HIV/HBV) coinfected patients, yet the associated immunological characteristics remain unclear. METHODS: Global and specific immune phenotypic profiles were examined in 48 patients with HIV/HBV coinfection before cART and at 1-year, and 3-year after cART using flow cytometry. In addition, 61 patients with HBV monoinfection were included for comparison. RESULTS: HBsAg response (sAg-R) was defined as > 0.5 log decrease within six months of cART initiation, and 16 patients achieved it. Patients with sAg-R (the sAg-R group) exhibited distinct immune phenotypes compared to those of HBsAg-retained patients (the sAg-NR group). Notably, patients with sAg-R had lower CD4+ T cell counts and a higher number of HBcAg-specific T cells. Further, the sAg-R group exhibited upregulation of HLA-DR, Ki67, and PD-1 in CD4+ T cells and heightened HLA-DR and T-bet in CD8+ T cells. However, the sAg-R group had fewer TEMRA cells but more TEM and Th17 cells than those in the sAg-NR group. Expression of various markers, including HLA-DR+CD4+, Ki67+CD4+, PD-1+CD4+, CD38+CD8+, HLA-DR+CD8+, TIM-3+CD8+, HBV-specific CD4+ T cell secreting IFN-γ and IL-2, and specific CD8+ T cell secreting IFN-γ and IL-2, correlated with HBsAg decrease. CONCLUSION: The decline in HBsAg levels during cART in HIV/HBV coinfection involves significant alterations in CD4+ and CD8+ T cells phenotypes, offering a novel perspective on a functional HBV cure.

Association of first-line combination antiretroviral therapy with malaria among adult HIV-infected persons in Jos, Nigeria: a pilot cross sectional study.

BACKGROUND: Malaria and human immunodeficiency virus (HIV) infection coexist in significant numbers in some geographic areas including sub-Sahara Africa (SSA). HIV-infected patients are a World Health Organization (WHO) recognized high risk group for increased malaria morbidity. Majority of HIV-infected patients undertaking treatment in SSA are on WHO recognized first-line combination antiretroviral therapy (cART). Considering the immunity-enhancing capacity of antiretroviral therapies on people living with HIV, this study aimed to explore the association between first-line combination antiretroviral therapy (cART) with malaria parasitaemia and antigenaemia in adult HIV-infected persons and to determine the predictors of malaria antigenaemia in adult persons living with HIV. METHODS: The study was conducted at the AIDS Prevention Initiative in Nigeria (APIN) Centre, Jos University Teaching Hospital, Jos, Plateau State, from August 2018 to February 2019. Epi Info statistical tool was used to determine the sample size and power of the study. The study population consisted of three groups. The first group comprised first-line cART-experienced adult HIV-seropositive subjects, the second group comprised ARV-naïve HIV-seropositive adults and the third group comprised HIV-seronegative adults. For this pilot study, 60 persons were recruited into each group via convenience sampling. Malaria rapid diagnostic test (RDT) was performed according to manufacturer's instruction for all the study participants using SD Bioline Malaria Ag P.f (HRP2/pLDH) (Standard Diagnostics, Hagal-Dong, Korea). All the study participants also had thick and thin blood film malaria microscopy. Data collected was processed and analyzed using the Stata statistical software version 15 (StataCorp, College Station, Texas). Chi square was used to test the association between malaria and first-line cART exposure. Univariate and multivariate analysis were also done to identify factors that were independently associated with malaria antigenaemia. RESULTS: A total of 180 persons participated in the study and involved 60 participants recruited in each of the three study groups. Overall, the predominant study participants were females (56.67%), traders (27.78%), secondary school leavers (43.33%) and urban dwellers (88.89%). Their mean age and standard deviation was 37.07 ± 11.53 years. Using malaria microscopy, the prevalence of malaria parasitaemia in ARV-naïve HIV-infected persons was 5% and 0% in the first-line cART-experienced HIV-infected persons as well as the HIV-negative persons. Malaria RDT result was positive in 7/60 (11.67%) of the first-line cART experienced HIV-infected participants, 6/60 (10%) of the ARV-naïve HIV-infected group and 1/60 (1.67%) of the HIV-negative group. Of the seven positive malaria RDT results in those on first-line cART, five persons were receiving zidovudine/lamivudine/nevirapine (AZT/3TC/NVP) while the remaining two were receiving tenofovir disoproxil fumarate/lamivudine/efavirenz (TDF/3TC/EFV), thus making an antigenaemia proportion of 16.67% and 6.67% respectively. Being an HIV-infected person on first-line cART (OR = 16.20, p = 0.04), having a headache (OR = 6.21, p = 0.03) and non-usage of window nets (OR = 3.74, p = 0.05) were found to be predictors of malaria antigenaemia. CONCLUSION: Malaria parasite burden in HIV-infected persons on first-line cART is lower than that observed in ARV-naïve HIV-infected persons. Our study suggests that TDF/3TC/EFV may be associated with lower malaria antigenaemia when compared with AZT/3TC/NVP and can be considered an alternative first-line antiretroviral regimen in malaria-endemic regions.

Acute myeloid leukemia following remission of AIDS-associated extra-nodal NK/T-cell lymphoma.

Background: AIDS-related NK/T-cell lymphoma is a rare subtype of AIDS-related lymphomas, characterized by a poor prognosis and lack of standardized treatment protocols. To date, there have been no reported cases of AIDS-associated NK/T-cell lymphoma in remission followed by treatment-related acute myeloid leukemia (t-AML), where both the lymphoma and AML achieved remission and long-term survival through chemotherapy alone. Case presentation: We report a case of a patient diagnosed with AIDS-related extra-nodal NK/T-cell lymphoma (ENKTCL). The patient achieved complete remission after receiving six cycles of chemotherapy, local radiotherapy, and combination antiretroviral therapy (cART). Throughout the follow-up period, the patient continued cART treatment, maintaining an HIV-RNA level below the lower limit of detection. However, 70 months later, the patient developed new symptoms and was subsequently diagnosed with acute myeloid leukemia (AML) M4 subtype. Following the completion of 10 cycles of chemotherapy and ongoing cART, the patient achieved complete remission of AML, with an overall survival time exceeding 103 months from the initial ENKTCL diagnosis. Conclusions: This case highlights the effectiveness of chemotherapy combined with cART in the treatment of AIDS-associated NK/T-cell lymphoma and secondary treatment-related leukemia. This approach may serve as a viable option for patients who are not candidates for bone marrow transplantation. Furthermore, this case underscores the importance of long-term follow-up in the management of AIDS-associated malignancies.

Effects of individual drug and combination antiretroviral therapy on trophoblast proliferation.

BACKGROUND: Combination antiretroviral therapy (cART) has been reported to reduce perinatal transmission of human immunodeficiency virus (HIV) and improve maternal survival outcomes. Recent studies have associated in-utero exposure to cART drugs with adverse outcomes such as pre-eclampsia, preterm delivery, low birth weight and small-for-gestational-age births. However, the exact molecular mechanisms underlying cART-induced adverse pregnancy outcomes remain poorly defined. OBJECTIVES: To investigate the effects of cART drugs on trophoblast proliferation in the HTR-8/SVneo cell line. STUDY DESIGN: HTR-8/SVneo cells were exposed to tenofovir (0.983-9.83 µM), emtricitabine (0.809-8.09 µM) and efavirenz (0.19-1.09 µM), the individual drugs of the first-line single tablet cART regimen termed 'Atripla', and zidovudine (1.12-1.12 µM), lamivudine (0.65-6.5 µM), lopinavir (0.32-3.2 µM) and ritonavir (0.69-6.9 µM), the individual drugs of the second-line single tablet cART regimen termed 'Aluvia'. The cells were treated for 24, 48, 72 and 96 h, and trophoblast proliferation was assessed using a colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltretrazolium bromide assay. RESULTS: Two-way analysis of variance showed a significant dose-dependent decrease (p < 0.05) in trophoblast proliferation in response to individual and combined drug components of first- and second-line antiretroviral therapy. CONCLUSIONS: First- and second-line cART drugs inhibit trophoblast proliferation, and may contribute to placenta-mediated adverse pregnancy outcomes in patients with HIV.

" So that's why we hide, we don't want them to know"- Challenges to Antiretroviral Therapy Adherence in Kampala, Uganda.

The aim of this study wasto advance knowledge of the social, geographical, and economic complexities faced by people on cART and to understand how they navigate treatment adherence within the urban context of Kampala, Uganda.Semi-structured interviews (n=30) were conducted with individuals receiving HIV treatment from the Joint Clinical Research Centre (JCRC) in Kampala. The thematic analysis of the interview transcripts was conducted in NVivo, with direct quotations from the transcripts used to illustrate key themes.It emerged from the interviews thatkeychallenges faced by people on HIV treatment include: the burden of the drug regimen, food insecurity, transportation and travel, and stigma.All participants frequently emphasized the negative effects of stigma on their daily lives, whether at work, at home or in transit. The study's participants also suggested that knowledge of HIV and HIV treatment is still lacking in their broader communities, which impacts how people living with HIV are perceived. Social processes such as stigmatization in public places must be considered by health policy makers, in orderto maximize treatment adherence. Efforts towards public sensitization can help to create social settings which allow those on HIV treatment to take their medication without fear of judgement.

A Review of FDA-Approved Anti-HIV-1 Drugs, Anti-Gag Compounds, and Potential Strategies for HIV-1 Eradication.

Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human immunodeficiency virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection from a fatal illness into a manageable chronic disorder. However, the presence of latent reservoirs, the multifaceted nature of HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict the efficacy of current cART targeting the distinct stages of the virus life cycle. Therefore, there is an unmet need for the discovery of new therapeutics that not only bypass the limitations of the current therapy but also protect the body's health at the same time. The main goal for complete HIV-1 eradication is purging latently infected cells from patients' bodies. A potential strategy called "lock-in and apoptosis" targets the budding phase of the life cycle of the virus and leads to susceptibility to apoptosis of HIV-1 infected cells for the elimination of HIV-1 reservoirs and, ultimately, for complete eradication. The current work intends to present the main advantages and disadvantages of United States Food and Drug Administration (FDA)-approved anti-HIV-1 drugs as well as plausible strategies for the design and development of more anti-HIV-1 compounds with better potency, favorable pharmacokinetic profiles, and improved safety issues.

Plasma Lipidomic Profiles in cART-Treated Adolescents with Perinatally Acquired HIV Compared to Matched Controls.

Children with perinatally acquired human immunodeficiency virus (PHIV) are growing into adulthood with HIV and treatment-associated comorbidities, such as dyslipidemia and insulin resistance. HIV is identified as independent risk factor for cardiovascular disease (CVD). The hypothesis behind increased CVD risk associated with HIV includes vascular inflammation, dyslipidemia and combination antiretroviral therapy (cART) metabolomic toxicity. To investigate differences in lipid profiles and pathophysiological mechanisms of CVD risk in adolescents with PHIV, we compared the plasma lipidome of PHIV adolescents and HIV-negative controls. We additionally investigated the influence of current cART regimens and increased lipoprotein(a) (Lp(a)) levels on the plasma lipidome. We included 20 PHIV-infected adolescents and 20 HIV-negative controls matched for age, sex, ethnic origin and socio-economic status. Plasma lipidome was measured using Thermo Scientific Ultimate 3000 binary high-performance liquid chromatography (HPLC)-mass spectrometry. We evaluated the plasma lipidome in PHIV adolescents using different cART regimens (including those known to be associated with lipid alterations). The median age was 17.5 years (15.5-20.7) and 16.5 years (15.7-19.8) for PHIV adolescents and controls, respectively. Of PHIV adolescents, 45% used a non-nucleotide reverse transcriptase inhibitor (NNRTI)-based (25%) or protease inhibitor (PI)-based (20%) cART regimen. In this pilot study, we observed no significant differences between lipidomic profiles between PHIV adolescents and controls. We observed no differences in the plasma lipidome in participants with increased versus normal Lp(a) levels. Different cART regimens appear to influence chain length differences in the plasma lipidome of PHIV adolescents; however, the significance and causality of this observation remains undetermined. Further research on the influence of cART on lipid composition could further identify these alterations.

Cardiometabolic Differences in People Living with HIV Receiving Integrase Strand Transfer Inhibitors Compared to Non-nucleoside Reverse Transcriptase Inhibitors: Implications for Current ART Strategies.

In people living with HIV (PLHIV), integrase strand transfer inhibitors (INSTIs) are part of the first-line combination antiretroviral therapy (cART), while non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are alternatives. Distinct cART regimens may variably influence the risk for non-AIDS comorbidities. We aimed to compare the metabolome and lipidome of INSTI and NNRTI-based regimens. The 2000HIV study includes asymptomatic PLHIV (n = 1646) on long-term cART, separated into a discovery cohort with 730 INSTI and 617 NNRTI users, and a validation cohort encompassing 209 INSTI and 90 NNRTI users. Baseline plasma samples from INSTI and NNRTI users were compared using mass spectrometry-based untargeted metabolomic (n = 500) analysis. Perturbed metabolic pathways were identified using MetaboAnalyst software. Subsequently, nuclear magnetic resonance spectroscopy was used for targeted lipoprotein and lipid (n = 141) analysis. Metabolome homogeneity was observed between the different types of INSTI and NNRTI. In contrast, higher and lower levels of 59 and 45 metabolites, respectively, were found in the INSTI group compared to NNRTI users, of which 77.9% (81/104) had consistent directionality in the validation cohort. Annotated metabolites belonged mainly to 'lipid and lipid-like molecules', 'organic acids and derivatives' and 'organoheterocyclic compounds'. In pathway analysis, perturbed 'vitamin B1 (thiamin) metabolism', 'de novo fatty acid biosynthesis', 'bile acid biosynthesis' and 'pentose phosphate pathway' were detected, among others. Lipoprotein and lipid levels in NNRTIs were heterogeneous and could not be compared as a group. INSTIs compared to individual NNRTI types showed that HDL cholesterol was lower in INSTIs compared to nevirapine but higher in INSTIs compared to doravirine. In addition, LDL size was lower in INSTIs and nevirapine compared to doravirine. NNRTIs show more heterogeneous cardiometabolic effects than INSTIs, which hampers the comparison between these two classes of drugs. Targeted lipoproteomic and lipid NMR spectroscopy showed that INSTI use was associated with a more unfavorable lipid profile compared to nevirapine, which was shifted to a more favorable profile for INSTI when substituting nevirapine for doravirine, with evidently higher fold changes. The cardiovascular disease risk profile seems more favorable in INSTIs compared to NNRTIs in untargeted metabolomic analysis using mass-spectrometry.

Electronic Medical Record Data Missingness and Interruption in Antiretroviral Therapy Among Adults and Children Living With HIV in Haiti: Retrospective Longitudinal Study.

Background: Children (aged 0-14 years) living with HIV often experience lower rates of HIV diagnosis, treatment, and viral load suppression. In Haiti, only 63% of children living with HIV know their HIV status (compared to 85% overall), 63% are on treatment (compared to 85% overall), and 48% are virally suppressed (compared to 73% overall). Electronic medical records (EMRs) can improve HIV care and patient outcomes, but these benefits are largely dependent on providers having access to quality and nonmissing data. Objective: We sought to understand the associations between EMR data missingness and interruption in antiretroviral therapy treatment by age group (pediatric vs adult). Methods: We assessed associations between patient intake record data missingness and interruption in treatment (IIT) status at 6 and 12 months post antiretroviral therapy initiation using patient-level data drawn from iSanté, the most widely used EMR in Haiti. Missingness was assessed for tuberculosis diagnosis, World Health Organization HIV stage, and weight using a composite score indicator (ie, the number of indicators of interest missing). Risk ratios were estimated using marginal parameters from multilevel modified Poisson models with robust error variances and random intercepts for the facility to account for clustering. Results: Data were drawn from 50 facilities and comprised 31,457 patient records from people living with HIV, of which 1306 (4.2%) were pediatric cases. Pediatric patients were more likely than adult patients to experience IIT (n=431, 33% vs n=7477, 23.4% at 6 months; P<.001). Additionally, pediatric patient records had higher data missingness, with 581 (44.5%) pediatric records missing at least 1 indicator of interest, compared to 7812 (25.9%) adult records (P<.001). Among pediatric patients, each additional indicator missing was associated with a 1.34 times greater likelihood of experiencing IIT at 6 months (95% CI 1.08-1.66; P=.008) and 1.24 times greater likelihood of experiencing IIT at 12 months (95% CI 1.05-1.46; P=.01). These relationships were not statistically significant for adult patients. Compared to pediatric patients with 0 missing indicators, pediatric patients with 1, 2, or 3 missing indicators were 1.59 (95% CI 1.26-2.01; P<.001), 1.74 (95% CI 1.02-2.97; P=.04), and 2.25 (95% CI 1.43-3.56; P=.001) times more likely to experience IIT at 6 months, respectively. Among adult patients, compared to patients with 0 indicators missing, having all 3 indicators missing was associated with being 1.32 times more likely to experience IIT at 6 months (95% CI 1.03-1.70; P=.03), while there was no association with IIT status for other levels of missingness. Conclusions: These findings suggest that both EMR data quality and quality of care are lower for children living with HIV in Haiti. This underscores the need for further research into the mechanisms by which EMR data quality impacts the quality of care and patient outcomes among this population. Efforts to improve both EMR data quality and quality of care should consider prioritizing pediatric patients.

12-week Dolutegravir treatment marginally reduces energy expenditure but does not increase body weight or alter vascular function in a murine model of Human Immunodeficiency Virus infection.

Combination antiretroviral therapy (cART) has markedly increased life expectancy in people with HIV (PWH) but has also resulted in an increased prevalence of cardiometabolic disorders, whose etiopathology remains ill-defined. Notably, the respective contribution of cART and HIV-derived proteins to obesity and vascular alterations remain poorly understood. Therefore, we investigated the individual and combined effects of HIV-proteins and of the integrase strand transfer inhibitor Dolutegravir (DTG) on body composition and vascular reactivity. Male wildtype (WT) and HIV transgenic (Tg26) mice, received DTG or vehicle for 12 weeks. Viral proteins expression in Tg26 mice lowered fat mass, increased heat production, and induced a 2-fold increase in brown adipose tissue (BAT) uncoupling protein 1 (UCP1) expression. DTG increased the expression of markers of adipogenesis in adipocytes in culture, but also reduced heat production and BAT UCP1 and UCP3 expression in Tg26 mice. DTG increased food intake, fat percentage and protected from lean mass reduction in Tg26 mice only. However, DTG did not increase body weight in either WT or Tg26 mice. Viral protein expression reduced acetylcholine (endothelium)-mediated relaxation by 14% in mesenteric arteries preconstricted with phenylephrine. However, DTG did not impair nor improve endothelium-dependent relaxation. Together, these data indicate that DTG's effects on food intake, adipogenesis and energy expenditure are insufficient to increase body weight, even in the presence of HIV-proteins, suggesting that body weight gain in PWH involves additional factors likely including other cART components and pre-existing comorbidities. Moreover, these data rule out DTG as a source of vascular disorders in PWH.

Management of immunosuppressive drugs in HIV-positive solid organ transplant recipients / 器官移植

The application of combination antiretroviral therapy (cART) has significantly prolonged the life expectancy of patients infected with human immunodeficiency virus (HIV). However, viral infection and adverse reactions of cART drugs make patients more prone to organ failure. Solid organ transplantation has become a standard treatment for HIV-infected patients with end-stage organ failure. Nevertheless, among HIV-positive soild organ transplant recipients, multiple problems remain to be resolved, such as increased incidence of graft rejection, increased infection risk, drug toxicity and drug interaction between cART therapy and immunosuppressive drugs, etc. It is extremely challenging to deliver appropriate management for HIV-positive soild organ transplant recipients. Therefore, the application of immune induction therapy, calcineurin inhibitors, mammalian target of rapamycin (mTOR) inhibitors and other immunosuppressive drugs in HIV-positive soild organ transplant recipients was reviewed, aiming to provide reference for subsequent management of immunosuppression in HIV-positive soild organ transplant recipients.

Ocular Manifestations of Human Immunodeficiency Virus Infection in the Combination Antiretroviral Therapy Era.

Since the introduction of combination antiretroviral therapy (cART) in Japan in 2008, the spectrum of ocular manifestations in patients with human immunodeficiency virus (HIV) has changed. This study, conducted at Tokyo Medical and Dental University Hospital between January 2012 and August 2023, aimed to understand the epidemiology and clinical features of ocular manifestations in patients with HIV during the cART era. Of the 218 patients diagnosed with HIV, 23 (10.55%) exhibited ocular manifestations; all were male, aged 32-73. The most prevalent ocular complication was uveitis (60.67%). Notably, the prevalence of uveitis in this cART era has surged compared to earlier Japanese studies. Our data also suggest a potential direct link between uveitis and HIV, particularly in patients who have not yet undergone cART. However, cytomegalovirus retinitis, another prevalent ocular disease in our study, appeared more strongly associated with patients who commenced cART. Neither ocular condition was significantly correlated with CD4+ T-cell count. Importantly, our observed ocular manifestation prevalence (10.55%) was lower than that in previous studies, emphasizing the potential influence of cART and national healthcare support. These findings provide unique insights into the evolution of ocular manifestations in patients with HIV in Japan amidst cART availability.

Lenacapavir: A Novel, Potent, and Selective First-in-Class Inhibitor of HIV-1 Capsid Function Exhibits Optimal Pharmacokinetic Properties for a Long-Acting Injectable Antiretroviral Agent.

Lenacapavir (LEN) is a picomolar first-in-class capsid inhibitor of human immunodeficiency virus type 1 (HIV-1) with a multistage mechanism of action and no known cross resistance to other existing antiretroviral (ARV) drug classes. LEN exhibits a low aqueous solubility and exceptionally low systemic clearance following intravenous (IV) administration in nonclinical species and humans. LEN formulated in an aqueous suspension or a PEG/water solution formulation showed sustained plasma exposure levels with no unintended rapid drug release following subcutaneous (SC) administration to rats and dogs. A high total fraction dose release was observed with both formulations. The long-acting pharmacokinetics (PK) were recapitulated in humans following SC administration of both formulations. The SC PK profiles displayed two-phase absorption kinetics in both animals and humans with an initial fast-release absorption phase, followed by a slow-release absorption phase. Noncompartmental and compartmental analyses informed the LEN systemic input rate from the SC depot and exit rate from the body. Modeling-enabled deconvolution of the input rates from two processes: absorption of the soluble fraction (minor) from a direct fast-release process leading to the early PK phase and absorption of the precipitated fraction (major) from an indirect slow-release process leading to the later PK phase. LEN SC PK showed flip-flop kinetics due to the input rate being substantially slower than the systemic exit rate. LEN input rates via the slow-release process in humans were slower than those in both rats and dogs. Overall, the combination of high potency, exceptional stability, and optimal release rate from the injection depot make LEN well suited for a parenteral long-acting formulation that can be administered once up to every 6 months in humans for the prevention and treatment of HIV-1.

Integrated analysis of viral blips, residual viremia, and associated factors in people with HIV: Results from a retrospective cohort study.

The etiology of viral blips is not yet fully elucidated. One of the hypotheses is that blips reflect variations in residual viremia (RV) near the detectability threshold. In this study, we evaluated whether RV is associated with viral blips and which factors are associated with RV. All treatment regimens in 2010-2020 consisting of two nucleos(-t)ide reverse transcriptase inhibitors and one anchor (integrase strand transfer inhibitor [INSTI], non-nucleoside reverse transcriptase inhibitor [NNRTI], or protease inhibitor [PI]) in people with HIV (PWH) were evaluated for RV (detectable viremia <50 cp/mL) and blips (isolated viral loads [VLs] 50-499 cp/mL between measurements <50 cp/mL). All medical records were reviewed and regimens in which a VL ≥ 50 cp/mL was deemed to result from non-adherence (based on the documented conclusion by the treating physician) were excluded. Factors associated with blips and RV were identified using generalized linear mixed models. In total, 24 518 VLs from 1658 PWH were analyzed. VLs were measured during INSTI- (n = 5119; 20.9%), PI- (n = 8935; 36.4%), and NNRTI-use (n = 10 464; 42.7%). VLs were categorized as blips in 1.4% (n = 332). The 24,186 non-blip VLs were RNAneg (no RV) (n = 15 326; 63.4%), 1-19 cp/mL (n = 6318; 26.1%), 20-49 cp/mL (n = 1620; 6.7%), or <50 cp/mL with an unknown RV level (n = 922; 3.8%). In 193/1658 PWH (11.6%), the RV level was RNAneg in all VLs assessed. RV 1-19 cp/mL and 20-49 cp/mL (vs. RNAneg ) were significantly associated with subsequent viral blips (respective odds ratio 2.66 and 4.90 [95% confidence intervals: 1.98-3.58 and 3.41-7.04]). Zenith VL and use of PIs (vs. INSTIs/NNRTIs) were associated with higher RV and blip odds. This large cohort study showed that blips were associated with higher preceding RV. Both the anchor type and factors previously linked to the latent viral reservoir were associated with RV, suggesting blips having a multifactorial origin.

Selected biochemical parameters in the urine of HIV-infected patients in monitoring of kidney function.

Introduction: For years, there has been an increase in the number of cases of chronic kidney disease (CKD) in human immunodeficiency virus (HIV)-infected patients. Renal dysfunction can be caused by direct effects of HIV on the kidneys but also of applied combined antiretroviral therapy (cART). Therefore there is a need of renal function diagnosis to monitor the development of kidney disturbances. In this study the urinary levels of selected low molecular weight proteins (LMWP) in HIV-infected patients were measured and related to current CD4+ T lymphocyte (LT CD4+) count, the glomerular filtration rate (eGFR) value and the applied cART. Material and methods: The levels of 5 LMWP - kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL), glutathione S-transferase α (GST-α) and π (GST-π) isoenzymes and neopterin (NPT) - in urine were measured in HIV-infected patients and healthy controls by enzyme-linked immunosorbent assay. Results: Taking into account the current LT CD4+ count, KIM-1, NGAL and GST-α showed statistically significant differences between groups with the CD4+ count < 500 and ≥ 500 cells (< 0.001). Depending on the eGFR, apart from KIM-1 and NGAL, NPT showed statistically significant differences in the investigated groups with normal and lower eGFR values (< 0.001). In terms of applied cART, the best parameters in the assessment of kidney damage were NGAL, GST-π and NPT (< 0.001). Conclusions: This research shows that the analyzed LMWP parameters are useful in the assessment of kidney damage in HIV patients during cART, especially NPT, NGAL and GST-π. However, future studies should be conducted on larger groups.

The Influence of Age-Associated Comorbidities on Responses to Combination Antiretroviral Therapy Among People Living with HIV, at the ART Clinic of Jimma Medical Center, Ethiopia: A Hospital-Based Nested Case-Control Study.

Introduction: Despite the high prevalence of age-associated comorbidities in HIV patients in sub-Saharan Africa, there is a lack of data on their influence on treatment outcomes in HIV patients. Therefore, this study aimed to assess the impact of age-associated comorbidities on responses to antiretroviral therapy (ART) among people living with HIV. Methods: A hospital-based nested case-control study was conducted among adult HIV-infected patients at the Jimma Medical Center from January 3 to June 2, 2022. Data were recorded by interviewing the patients and their medical chart and analyzed using The Statistical Package for Social Science (SPSS) v. 23, and at p <0.05. The Results: The overall immunological and virologic failure rates were 13.8% and 13.4%, respectively. Being male [AOR = 3.079,95% CI (1.139-8.327)], having age-associated comorbidity [AOR:10.57,95% CI (2.810-39.779)], age ≥ 50 years [AOR = 2.855, 95% CI (1.023-7.9650)], alcohol intake [AOR = 3.648,95% CI (1.118-11.897)], and having a baseline CD4+ count of < 200 cells/uL [AOR:3.862, 95% CI (1.109-13.456) were an independent predictor of immunological failure; Whereas Being alcoholic [AOR:3.11, 95% CI (1.044-9.271)], having a baseline CD4+ count of < 200 cells/uL [AOR:5.11, 95% CI (1.547-16.892)], a low medication adherence [AOR:5.92, 95% CI (1.81-19.36)], bedridden baseline functional status [AOR:3.902, 95% CI (1.237-12.307)], and lack of cotrimoxazole prophylaxis [AOR:2.735,95% CI (1.084-6.902)] were found to be an independent predictor of virologic treatment failure, but being younger (age < 50 years) was protective for virologic failure. Conclusion: Out of the eight patients who were treated for HIV at least one patient had developed immunological and/or virological failure. Age-associated comorbid chronic non-communicable diseases highly influence immunological outcomes compared with virological outcomes. Health providers should pay attention to age-associated comorbidities, encourage lifestyle modifications, and counsel on medication adherence to improve clinical outcomes in patients with HIV.

Contemporary Antiretroviral Therapy Dysregulates Iron Transport and Augments Mitochondrial Dysfunction in HIV-Infected Human Microglia and Neural-Lineage Cells.

HIV-associated cognitive dysfunction during combination antiretroviral therapy (cART) involves mitochondrial dysfunction, but the impact of contemporary cART on chronic metabolic changes in the brain and in latent HIV infection is unclear. We interrogated mitochondrial function in a human microglia (hµglia) cell line harboring inducible HIV provirus and in SH-SY5Y cells after exposure to individual antiretroviral drugs or cART, using the MitoStress assay. cART-induced changes in protein expression, reactive oxygen species (ROS) production, mitochondrial DNA copy number, and cellular iron were also explored. Finally, we evaluated the ability of ROS scavengers or plasmid-mediated overexpression of the antioxidant iron-binding protein, Fth1, to reverse mitochondrial defects. Contemporary antiretroviral drugs, particularly bictegravir, depressed multiple facets of mitochondrial function by 20-30%, with the most pronounced effects in latently infected HIV+ hµglia and SH-SY5Y cells. Latently HIV-infected hµglia exhibited upregulated glycolysis. Increases in total and/or mitochondrial ROS, mitochondrial DNA copy number, and cellular iron accompanied mitochondrial defects in hµglia and SH-SY5Y cells. In SH-SY5Y cells, cART reduced mitochondrial iron-sulfur-cluster-containing supercomplex and subunit expression and increased Nox2 expression. Fth1 overexpression or pre-treatment with N-acetylcysteine prevented cART-induced mitochondrial dysfunction. Contemporary cART impairs mitochondrial bioenergetics in hµglia and SH-SY5Y cells, partly through cellular iron accumulation; some effects differ by HIV latency.

Prevalence, Awareness, Treatment, Control of Hypertension, and Availability of Hypertension Services for Patients Living With Human Immunodeficiency Virus (HIV) in Sub-Saharan Africa (SSA): A Systematic Review and Meta-analysis.

Sub-Saharan Africa (SSA) is faced with a dual burden of hypertension and human immunodeficiency virus (HIV). In this review we sought to determine the prevalence, awareness, and control of hypertension among persons living with HIV (PLHIV), and the availability of hypertension services at the HIV care points in SSA. We searched the PubMed, Embase, Scopus, Cochrane library, Global index Medicus, African Journal online, and WHO Institutional Repository for Information Sharing (IRIS) for studies on the epidemiology of hypertension, and hypertension services for PLHIV in SSA. Twenty-six articles were identified for the review, with 150,886 participants; weighted mean of age 37.5 years and female proportion of 62.6%. The pooled prevalence was 19.6% (95% confidence interval [CI], 16.6%, 22.5%); hypertension awareness was 28.4% (95% CI, 15.5%, 41.3%), and hypertension control was 13.4% (95% CI, 4.7%, 22.1%). HIV-related factors like CD4 count, viremia, and antiretroviral therapy regimen were not consistently associated with prevalent hypertension. However, high body mass index (BMI) above 25 kg/m2 [odds ratio: 1.64, 95% CI (1.26, 2.02)] and age above 45 years [odds ratio: 1.44, 95% CI (1.08, 1.79)] were associated with prevalent hypertension. Even when PLHIV on ART were more likely to be screened for hypertension and monitored, there was infrequent screening and treatment of hypertension in most HIV clinics. Most studies recommended integrating of HIV and hypertension services. We report a high prevalence of hypertension in a relatively young population of PLHIV with suboptimal screening, treatment, and control of hypertension. We recommend strategies to integrate HIV and hypertension services.

Rapidly Disseminated Kaposi's Sarcoma Despite Initiation of Antiretroviral Therapy.

Kaposi's sarcoma (KS) is the most common malignancy in people living with HIV. The reported incidence of AIDS-related KS has been dramatically decreased with the introduction of antiretroviral therapy (ART). Systemic treatment with ART is indicated for patients with AIDS-related KS; however, some patients may develop KS-related immune reconstitution inflammatory syndrome characterized by sudden rapid progression of new or pre-existing KS within the initiation of ART. Here, we present a case of rapidly disseminated KS with widespread visceral involvement despite ART initiation in a 27-year-old African American man with advanced HIV/AIDS.