Undetectable Plasma Viral Load Research Articles

Semen Washing and Intrauterine Insemination for Reducing the Risk of Human Immunodeficiency Virus Transmission in Serodiscordant Couples: A Cross-sectional Study

ABSTRACT Background: Antiretroviral therapy has helped human immunodeficiency virus (HIV)-infected people live an enhanced quality of life and attempt for a pregnancy, without placing their partner at risk. Although periconceptional pre-exposure prophylaxis for the uninfected partner and consistent antiretroviral therapy for the HIV-infected partner are important to prevent HIV transmission, semen washing could be a great option to further reduce the semen viral load. Aim: The aim of this study were as follows: to determine if semen washing with intrauterine insemination provides an added safety net to HIV-serodiscordant couples when the male partner is HIV-infected and virally suppressed and to determine if the U = U concept (undetectable = untransmittable) holds true in virally suppressed HIV-infected males. Settings and Design: This was an observational study conducted in seropositive HIV men under treatment with highly active antiretroviral therapy (HAART) in collaboration with Metropolis Laboratory, a CAP recognised private Healthcare Laboratory in Mumbai, India. Materials and Methods: Blood and semen samples were collected from a total of 110 adult HIV-1-infected males virally suppressed on HAART. These samples were processed to assess the viral load in plasma as well as raw and processed semen fractions. Statistical Analysis Used: Descriptive statistics were used to analyse the data. Results: Only men with plasma viral loads < 1000 copies were selected in our study. Out of the 110 HIV-infected individuals, 102 (92.73%) patients had undetectable (<20 copies/ml) plasma viral load while 8 (7.27%) patients had a detectable (>20 copies/ml) viral load, who were excluded from the study. In the virally suppressed 102 men, the raw semen samples of 100 men showed an undetectable viral load, while 2 samples showed detectable contamination, even though their plasma samples from the blood showed a viral load of <20 copies/ml. The semen was then separated into the sperm and the seminal plasma samples. The seminal plasma had <20 copies/ml in 95 samples (93.14%) but a detectable viral load in 7 (6.86%) samples. After subjecting all the 102 processed (post-wash) sperm samples to quantitative analysis, an undetectable viral load of <20 copies/ml was found in all the samples. Thus, the raw sample (prewashed),seminal plasma and processed (postwash) samples were evaluated. The post-wash sperm sample showing zero contamination was frozen for intrauterine insemination (IUI) in the uninfected female partner. Conclusions: Semen washing with IUI should be advocated as a safe, efficacious way to increase the safety net and to further reduce the minimal risk of HIV transmission in serodiscordant couples in addition to the U = U concept.

Cerebrospinal Fluid Viral Escape on Highly Active Antiretroviral Therapy: Analysis from Single Tertiary Care Centre.

HIV-infected individuals receiving regular antiretroviral therapy (ART) can present with a high viral load in cerebrospinal fluid (CSF) at times when it is suppressed in blood. This study presents data of HIV-infected patients who had undetectable or low plasma viral load in blood but presented with neurological signs and symptoms and were diagnosed to have CSF HIV viral escape. Records were reviewed for clinical manifestations, details of opportunistic or coinfection, and HIV viral copies in plasma and CSF at time of diagnosis of CSF escape. A total of 10,200 HIV-infected individuals were registered in HIV care till December 31, 2021. Nineteen individuals (14 virologically confirmed and 5 clinically) were diagnosed with high viral copies in CSF from June 2014 to December 2021. Mean age was 41.5 ± 9.2 (median, 39.5; range, 30-62) years. Average duration of antiretroviral treatment received at the time of diagnosis of CSF escape was 10.1 years. Median plasma HIV-viral copies were 2,469.8 (undetectable to 29,418) and in CSF were 12,773.7 (n = 14, range, 1,340-48,530) copies/mL. HIV viral copies in CSF were significantly higher than in plasma at the time of presentation (p = .003). ART regimen switch was done after identification of HIV CSF escape. Seventeen patients were alive with a regular follow-up of average 35 (range 7-66) months. All had documented clinical improvement with reversal of neurological impairment after ART switch. There was one death and one lost to follow-up. Early identification and timely intervention in CSF viral escape could revert severe neurological impairment and improves treatment outcome.

Serum Amylase Activity in Children Living with HIV-1 at the Charles de Gaulle Pediatric University Hospital in Ouagadougou

Biological monitoring is an essential part of the management of HIV infection. The aim of this study was to assess serum amylase activity during follow-up of children living with HIV-1 (CLHIV-1) at the Charles de Gaulle Pediatric University Hospital (CHUP-CDG). This was a descriptive and analytical cross-sectional study, with retrospective data collection from January 1, 2020 to December 31, 2022. Patients under 15 years of age who were being monitored for HIV-1 at CHUP-CDG and who had undergone a serum amylase assay during the study period were included. A total of 746 patients have been included, with a M/F sex ratio of 0.91 and a mean age of 8.52±4.08 years. Among CLHIV-1, 88.05% had a TCD4 lymphocyte count > 500/mm<sup>3</sup> and 60.32% an undetectable plasma viral load (PVL). The incidence of hyperamylasemia in the study population was 57.64%. Hyperamylasemia was significantly more frequent in children aged 0-2 years (<i>p<0.00001</i>), in patients with a high PVL (<i>p=0.0016</i>) and in those on the protocol combining two nucleoside reverse transcriptase inhibitors with a protease inhibitor. Several abnormalities in serum amylase activity were detected in CLHIV-1 during the course of the study. Clinical correlation and adequate follow-up of these abnormalities are essential to reduce the morbidity and mortality associated with pancreatic damage in people living with HIV.

An Automated Virtual Reality Program Accurately Diagnoses HIV-Associated Neurocognitive Disorders in Older People With HIV.

HIV-associated neurocognitive disorders (HANDs) remain prevalent despite antiretroviral therapy, particularly among older people with HIV (PWH). However, the diagnosis of HAND is labor intensive and requires expertise to administer neuropsychological tests. Our prior pilot work established the feasibility and accuracy of a computerized self-administered virtual reality program (DETECT; Display Enhanced Testing for Cognitive Impairment and Traumatic Brain Injury) to measure cognition in younger PWH. The present study expands this to a larger sample of older PWH. We enrolled PWH who were ≥60 years old, were undergoing antiretroviral therapy, had undetectable plasma viral loads, and were without significant neuropsychological confounds. HAND status was determined via Frascati criteria. Regression models that controlled for demographic differences (age, sex, education, race/ethnicity) examined the association between DETECT's cognition module and both HAND status and Global Deficit Score (GDS) derived via traditional neuropsychological tests. Seventy-nine PWH (mean age, 66 years; 28% women) completed a comprehensive neuropsychological battery and DETECT's cognition module. Twenty-five (32%) had HAND based on the comprehensive battery. A significant correlation was found between the DETECT cognition module and the neuropsychological battery (r = 0.45, P < .001). Furthermore, in two separate regression models, HAND status (b = -0.79, P < .001) and GDS impairment status (b = -0.83, P < .001) significantly predicted DETECT performance. Areas under the curve for DETECT were 0.78 for differentiating participants by HAND status (HAND vs no HAND) and 0.85 for detecting GDS impairment. The DETECT cognition module provides a novel means to identify cognitive impairment in older PWH. As DETECT is fully immersive and self-administered, this virtual reality tool holds promise as a scalable cognitive screening battery.

Low-level of HIV-1 Seroreversion among People on Successful Antiretroviral Therapy in Cameroon: Implications for Clinical Monitoring in Resource-limited Settings

Background: Initiating early HIV treatment results to sustained viral suppression, reduced viral reservoirs and prompt immune reconstitution that may lead to HIV seronegativity (seroreversion). Seroreversion can be misinterpreted, leading to inappropriate clinical considerations. We thus sought to determine the HIV seroreversion among antiretroviral therapy (ART)-experienced Cameroonians. Method: A laboratory-based cross-sectional study was conducted among ART-experienced individuals with undetectable plasma viral load (less than 40 copies/mL) in 2019 at the Chantal BIYA International Reference Centre in Yaounde-Cameroon. On all blood samples, HIV antibody testing was performed using two rapid diagnostic tests (RDTs), followed by enzyme-linked immunosorbent assay. On non-reactive samples, proviral DNA was tested on on dried blood spots (DBS) specimens. Results: Of the 546 participants on ART (median ART duration : 5 years) and all experiencing a successful ART (VL&lt;40 copies/ml), only 01% (5/546) had shown HIV negative results. Of these five non-reactive cases, only one case (0.18%) was non-reactive to HIV RDTs but reactive to ELISA, and four cases (0.72%) were non-reactive to both RDTs and ELISA. These four samples were also negative for HIV proviral DNA, indicating potential absence of infection or an optimal control of viral replication. Conclusion: Seroreversion of HIV-1 infection is possible but may occur rarely among HIV-infected Cameroonians who are on successful ART. The few cases of HIV negativity on serology and DBS-PCR (proviral DNA) underscores the need for deeper HIV proviral DNA testing (on PBMC) to guide either continuous ART, detect possible functional cure, or events of HIV misdiagnosis in an era of declining prevalence.

Penatalaksanaan HIV dalam Kehamilan

HIV infection has been a global epidemic around the world. in the absence of intervention, the rates of HIV transmission during pregnancy, labor or breastfeeding vary from 15-45%. Data from Indonesia Health ministry 2011 shows 21.103 pregnancy women who undergone HIV test 534 (2,5%) are positive HIV infected. The use of antiretroviral (ARV) drugs has been success prevent mother to child transmission. Zidovudine monotherapy shows transmission rates (4,8%) higher than ARV combination. ARV combination that can use during pregnancy vary from triple NRTI, 2 NRTI + NNRTI, or 2 NRTI + PI with similar high virological supression rates. it has beeen shows a changing trend from sectio caesar to vaginal delivery with decrease of viral load using ARV combination, with increase percentage for vaginal delivery from 17% to 52%. Women who receive &gt;9 weeks pre partum prophylaxis significantly have undetectable viral load in plasma and breast milk during labor.

Thymic Exhaustion and Increased Immune Activation Are the Main Mechanisms Involved in Impaired Immunological Recovery of HIV-Positive Patients under ART.

Decades of studies in antiretroviral therapy (ART) have passed, and the mechanisms that determine impaired immunological recovery in HIV-positive patients receiving ART have not been completely elucidated yet. Thus, T-lymphocytes immunophenotyping and cytokines levels were analyzed in 44 ART-treated HIV-positive patients who had a prolonged undetectable plasma viral load. The patients were classified as immunological non-responders (INR = 13) and immunological responders (IR = 31), according to their CD4+ T cell levels. Evaluating pre-CD4+ levels, we observed a statistically significant trend between lower CD4+ T cell levels and INR status (Z = 3.486, p < 0.001), and during 18 months of ART, the CD4+ T cell levels maintained statistical differences between the INR and IR groups (WTS = 37.252, p < 0.001). Furthermore, the INRs were associated with an elevated age at ART start; a lower pre-treatment CD4+ T cell count and a percentage that remained low even after 18 months of ART; lower levels of recent thymic emigrant (RTE) CD4+ T cell (CD45RA + CD31+) and a naïve CD4+ T cell (CD45RA + CD62L+); higher levels of central memory CD4+ T cells (CD45RA-CD62L+); and higher immune activation by CD4+ expressing HLA-DR+ or both (HLA-DR+ and CD38+) when compared with IRs. Our study demonstrates that thymic exhaustion and increased immune activation are two mechanisms substantially implicated in the impaired immune recovery of ART-treated HIV patients.

Antigen Presenting Cell-Mediated HIV-1 Trans Infection in the Establishment and Maintenance of the Viral Reservoir

Despite potent antiretroviral therapy (ART), an HIV-1 reservoir persists that represents a major barrier to a cure. Understanding the mechanisms by which the HIV-1 reservoir is established and maintained is critical for the discovery of effective treatments to significantly reduce or eliminate the viral reservoir. In addition to cis infection, in which HIV-1 directly infects target CD4+ T cells, cell-to-cell transmission, or trans infection, can also occur. HIV-1 trans infection is significantly more efficient than cis infection, mostly due to the occurrence of multiple infections per cell during transfer. Additionally, trans infection is efficient even in the presence of ART and/or neutralizing antibodies. Cell-to-cell transmission is mediated by CD4+ T cells and professional antigen presenting cells (APC). Here we focus on APC, i.e., myeloid dendritic cells, B lymphocytes, and monocytes/macrophages, that bind, internalize, and transfer HIV-1 to target CD4+ T cells via various proposed mechanisms. We assess the potential impact of trans infection on the establishment and maintenance of the HIV-1 reservoir including its role in disease progression. We consider the natural interactions between APC and CD4+ T cells in vivo that HIV-1 may hijack, allowing for the highly efficient trans infection of CD4+ T cells, maintaining the viral reservoirs in tissue despite undetectable plasma viral loads in peripheral blood. We propose that these modes of viral pathogenesis need to be addressed in potential cure strategies to ensure eradication of the viral reservoir.

The Persistence of HIV Diversity, Transcription, and Nef Protein in Kaposi's Sarcoma Tumors during Antiretroviral Therapy.

Epidemic Kaposi's sarcoma (KS), defined by co-infection with Human Herpes Virus 8 (HHV-8) and the Human Immunodeficiency Virus (HIV), is a major cause of mortality in sub-Saharan Africa. Antiretroviral therapy (ART) significantly reduces the risk of developing KS, and for those with KS, tumors frequently resolve with ART alone. However, for unknown reasons, a significant number of KS cases do not resolve and can progress to death. To explore how HIV responds to ART in the KS tumor microenvironment, we sequenced HIV env-nef found in DNA and RNA isolated from plasma, peripheral blood mononuclear cells, and tumor biopsies, before and after ART, in four Ugandan study participants who had unresponsive or progressive KS after 180-250 days of ART. We performed immunohistochemistry experiments to detect viral proteins in matched formalin-fixed tumor biopsies. Our sequencing results showed that HIV diversity and RNA expression in KS tumors are maintained after ART, despite undetectable plasma viral loads. The presence of spliced HIV transcripts in KS tumors after ART was consistent with a transcriptionally active viral reservoir. Immunohistochemistry staining found colocalization of HIV Nef protein and tissue-resident macrophages in the KS tumors. Overall, our results demonstrated that even after ART reduced plasma HIV viral load to undetectable levels and restored immune function, HIV in KS tumors continues to be transcriptionally and translationally active, which could influence tumor maintenance and progression.

Clinical Reasoning: Rapidly Progressive Dementia in a Man With HIV Infection and Undetectable Plasma Viral Load.

Neurocognitive decline associated with HIV infection remains prevalent even in the antiretroviral therapy (ART) era, albeit usually in less severe forms. The differential diagnosis of cognitive impairment in this population is quite broad, including infectious causes such as CNS opportunistic infections, causes directly related to HIV such as HIV-associated neurocognitive disorders, and causes entirely unrelated to HIV infection such as primary dementia syndromes. In this case report, a 47-year-old man with HIV on ART with an undetectable plasma viral load presented with rapidly progressive dementia to a clinic in Zambia. He had been functioning independently and fully employed before symptom onset but had to stop working within 2 months of symptom onset because of the severity and rapidity of his cognitive decline. Initial workup led to an empiric diagnosis and initiation of an empiric treatment regimen, which was ultimately ineffective. This prompted re-evaluation, additional workup, and, ultimately, discovering the correct diagnosis. This case highlights the stepwise approach to developing a diagnosis in a resource-limited setting where there exists a high burden of HIV infection, including the necessity of empiric diagnoses of treatment plans when investigations are limited and the importance of reconsidering these diagnoses in the face of additional clinical information. In addition, it highlights both infectious and noninfectious causes of cognitive decline in people with HIV.

Immunological and virological findings in a patient with exceptional post-treatment control: a case report

Although antiretroviral therapy (ART) is effective in suppressing viral replication, HIV-1 persists in reservoirs and rebounds after ART has been stopped. However, a very few people (eg, elite and post-treatment controllers) are able to maintain viral loads below detection limits without ART, constituting a realistic model for long-term HIV remission. Here, we describe the HIV control mechanisms of an individual who showed exceptional post-treatment control for longer than 15 years. We report the case of a Hispanic woman aged 59 years with sexually acquired acute HIV infection, who was included in an immune-mediated primary HIV infection trial involving a short course of ciclosporine A, interleukin-2, granulocyte macrophage colony-stimulating factor, and pegylated interferon alfa, followed by analytical treatment interruption. We did the following viral assays: total and integrated HIV-1 DNA in CD4 T cells and rectal tissue, quantitative viral outgrowth assay, HIV-1 infectivity in peripheral blood mononuclear cells and CD4 T-cell cultures and viral inhibitory activity by natural killer (NK) and CD8 T cells. NK and T-cell phenotypes were determined by flow cytometry. HLA, killer cell immunoglobulin-like receptors, Δ32CCR5, and NKG2C alleles were genotyped. After ART and immunomodulatory treatment, the person maintained undetectable plasma viral load for 15 years. HIV-1 subtype was CFR_02AG, CCR5-tropic. We found progressive reductions in viral reservoir during the 15-year treatment interruption: total HIV DNA (from 4573·50 copies per 106 CD4 T cells to 95·33 copies per 106 CD4 T cells) and integrated DNA (from 85·37 copies per 106 CD4 T cells to 5·25 copies per 106 CD4 T cells). Viral inhibition assays showed strong inhibition of in vitro HIV replication in co-cultures of CD4 T cells with autologous NK or CD8 T cells at 1:2 ratio (75% and 62%, respectively). Co-cultures with NK and CD8 T cells resulted in 93% inhibition. We detected higher-than-reference levels of both NKG2C-memory-like NK cells (46·2%) and NKG2C γδ T cells (64·9%) associated with HIV-1 control. We described long-term remission in a woman aged 59 years who was treated during primary HIV infection and has maintained undetectable viral load for 15 years without ART. Replication-competent HIV-1 was isolated. NKG2C-memory-like NK cells and γδ T cells were associated with the control viral replication. Strategies promoting these cells could bring about long-term HIV remission. Fondo Europeo para el Desarrollo Regional (FEDER), SPANISH AIDS Research Network (RIS), Fondo de Investigación Sanitaria (FIS), HIVACAT, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CERCA Programme/Generalitat de Catalunya, la Caixa Foundation, and Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC). For the Spanish translation of the abstract see Supplementary Materials section.

Association between gut microbiota and prediabetes in people living with HIV.

The prevalence of prediabetes is rapidly increasing in general population and in people living with HIV (PLWH). Gut microbiota play an important role in human health, and dysbiosis is associated with metabolic disorders and HIV infection. Here, we aimed to evaluate the association between gut microbiota and prediabetes in PLWH. A cross-sectional study enrolled 40 PLWH who were receiving antiretroviral therapy and had an undetectable plasma viral load. Twenty participants had prediabetes, and 20 were normoglycemic. Fecal samples were collected from all participants. The gut microbiome profiles were analyzed using 16S rRNA sequencing. Alpha-diversity was significantly lower in PLWH with prediabetes than in those with normoglycemia (p<0.05). A significant difference in beta-diversity was observed between PLWH with prediabetes and PLWH with normoglycemia (p<0.05). Relative abundances of two genera in Firmicutes (Streptococcus and Anaerostignum) were significantly higher in the prediabetes group. In contrast, relative abundances of 13 genera (e.g., Akkermansia spp., Christensenellaceae R7 group) were significantly higher in the normoglycemic group. In conclusion, the diversity of gut microbiota composition decreased in PLWH with prediabetes. The abundances of 15 bacterial taxa in the genus level differed between PLWH with prediabetes and those with normoglycemia. Further studies on the effect of these taxa on glucose metabolism are warranted.

Intracranial vascular imaging detects arterial wall abnormalities in persons with treated HIV infection.

Although a substantial proportion of ischemic strokes in persons with HIV infection (PWH) is related to large artery disease, studies evaluating elevated cerebrovascular risk in PWH have focused primarily on microvascular disease. We compared the burden of intracranial large artery disease on vessel wall MRI (VW-MRI) in PWH and HIV-uninfected individuals. Cross-sectional study. We recruited antiretroviral therapy-treated PWH with undetectable plasma viral load and HIV-uninfected individuals. All participants were at least 40 years of age and at moderate-to-high cardiovascular risk. We used Poisson and mixed effects logistic regression models to compare the number and associated characteristics of enhancing intracranial arteries on VW-MRI by HIV status. Of 46 participants (mean age 59 years), 33 were PWH. PWH had nearly four-fold as many enhancing intracranial arteries on VW-MRI than HIV-uninfected individuals (rate ratio 3.94, 95% CI 1.57-9.88, P = 0.003). The majority of wall enhancement was eccentric (76%) and short-segment (93%), suggestive of intracranial atherosclerotic disease (ICAD). Sixty-nine percent of enhancing arteries were not associated with luminal narrowing on magnetic resonance angiography (MRA). None of these characteristics differed significantly by HIV status. In persons at moderate-to-high cardiovascular risk, HIV infection, even when well controlled, may be associated with a greater burden of intracranial large artery disease and, specifically, of ICAD. Studies of the mechanisms underlying higher rates of ischemic stroke in PWH should include evaluation for intracranial large artery disease. VW-MRI provides added value as an adjunct to traditional luminal imaging when evaluating cerebrovascular risk in PWH.

Inflammatory Biomarkers in the Pathogenesis of Respiratory Dysfunction in People Living with HIV

Although the association between HIV infection and airways obstruction is well known, its etiopathogenesis is not clear. Our aim was to analyze the association between biomarkers of systemic inflammation and bacterial translocation and pulmonary function tests in HIV infected patients and compare it between smokers and non-smokers. Cross-sectional, observational study. Inclusion criteria: people living with HIV with undetectable plasma viral load. Exclusion criteria: other comorbidities associated with systemic inflammation. Outcome variables: spirometry and diffusing capacity for carbon monoxide; explanatory variables: inflammatory biomarkers (interleukin-6, tumor necrosis factor-alpha), bacterial translocation (soluble CD14 [sCD14] and bacterial 16S rDNA), and variables related to HIV infection. Associations were tested using the Pearson/Spearman correlation tests, the student t test, and multivariable linear regression. We included 71 patients (54.9% smokers). We did not observe significant differences in pulmonary function tests according to biomarkers of inflammation or bacterial translocation. In non-smokers (n=32), sCD14 was negatively correlated with forced expiratory volume in 1 second (R = -0.35, P = 0.048) and forced vital capacity (R= -0.40, P=0.023). Age, time since HIV diagnosis and CD4+ nadir were associated with alterations in PFTs. In smokers, the only association observed was between the pack-years and pulmonary obstruction. In non-smokers HIV patients, lung dysfunction can be, at least partially, related to bacterial translocation (sCD14), CD4+ nadir and time since HIV diagnosis.

Brief Report: Vaginal Viral Shedding With Undetectable Plasma HIV Viral Load in Pregnant Women Receiving 2 Different Antiretroviral Regimens: A Randomized Clinical Trial.

Pregnant women using antiretrovirals (ARVs) may have persistent vaginal viral shedding, which could be associated with sexual and perinatal HIV transmission. However, there are scant data on vaginal viral load (VVL) in pregnant women with undetectable plasma viral load (PVL). This study was a post hoc analysis of an open-label randomized trial to evaluate the virologic response of 2 ART regimens. The participants were ART-naive women living with HIV initiating ART regimens between 20 and 36 weeks of pregnancy recruited at 19 clinical sites in 6 countries. Participants were randomized to receive 400 mg of raltegravir 2 times a day or 600 mg of efavirenz 4 times a day in addition to 150 mg of lamivudine and 300 mg of zidovudine 2 times a day. VVL and PVL tests were performed at every study visit. The primary outcome measures were HIV-1 PVL and VVL at maternal study week 4 and rates of perinatal HIV transmission. A total of 408 were enrolled, of whom 323 had VVL samples 4 weeks after enrollment and were included in this analysis. Among women with undetectable/nonquantifiable PVL during ART, the overall rate of quantifiable VVL at week 4 was 2.54% (7/275). Of the 275 with nonquantifiable PVL, 99.1% (115/116) and 96.2% (153/159) had nonquantifiable VVL in the efavirenz and raltegravir arms, respectively. None of the 7 women with quantifiable VVL at the week 4 study visit transmitted HIV to their infants. Detectable VVL in pregnant women with undetectable/nonquantifiable PVL while receiving ART was rare and not associated with perinatal HIV transmission.

Clinical outcomes of pharmaceutical care intervention in HIV positive patients with hypertension: A randomized controlled study.

Pharmaceutical care (PC) has been shown to improve clinical outcomes in hypertensive patients as well as in people living with HIV (PLWHV). The objective of this study was to evaluate the impact of PC on blood pressure (BP) control, viral load and adherence to medications in hypertensive PLWHV. This was a prospective, randomized controlled study conducted in the University of Uyo Teaching Hospital, Uyo, Akwa Ibom State, Nigeria. Eligible ambulatory patients were randomized equally to two study arms. The control arm (CA) received the traditional care offered at the HIV clinic; the intervention arm (IA) received the traditional care in addition to PC by the research pharmacist, which included structured education/counselling. BP and self-reported medication adherence were measured at baseline, 6months and 12months. Viral load was obtained at baseline and after 12months. Data were analysed with spss, version 25.0. Of the 206 participants initially randomized, 182 (91 in each study arm) completed the 12-month follow-up. No significant differences existed in both arms concerning socio-demographic/clinical characteristics of participants at baseline (p>0.05). After 12months, BP control was significantly higher in the IA (53.4% vs. 25.2%; p<0.001, adjusted odds ratio, aOR=3.20 (95% CI 1.59-6.44). Systolic BP reduced by 0.9mmHg from baseline in the CA (p=0.668) and by 16.67mmHg from baseline value in the IA (p<0.001). Diastolic BP increased by 1.9mmHg in the CA (p=0.444), but reduced by 7.0mmHg in the IA (p<0.001). No significant differences were observed in the change from baseline in the proportion with undetectable plasma viral load (UPVL) in both groups (p>0.05). PC led to an increase in mean adherence to antiretroviral drugs (Δ=0.55; p=0.015), and an increase in mean adherence to antihypertensive drugs (Δ=2.32; p<0.001) in the IA. To our knowledge, this is the first prospective randomized controlled study evaluating the impacts of PC on clinical outcomes in hypertensive PLWHV with a 12-month follow-up. Our results show that PC significantly improved BP control and adherence to antiretroviral and antihypertensive medications, but had no significant effect on viral load in HIV positive patients with hypertension. Providers of care for PLWHV should leverage the established HIV treatment successes for promoting adherence to treatment for common comorbidities like hypertension in PLWHV in order to improve clinical outcomes.

Expression of Inflammatory Markers RANK, MMP-9 and PTHrP in Chronic Apical Periodontitis from People Living with HIV Undergoing Antiretroviral Therapy.

To compare the expression of the receptor activator of nuclear factor-kappa B (RANK), matrix metalloproteinase 9 (MMP-9) and parathyroid hormone-related protein (PTHrP) in primary chronic apical periodontitis lesions (CAPLs) between people living with HIV (PLWHIV) undergoing antiretroviral therapy (ART) and HIV- individuals, 32 CAPLs (16 lesions from each group) were submitted to histopathological and immunohistochemical analyses and compared between groups. The majority of the PLWHIV group had undetectable plasma viral loads (n = 13; 81.3%). The means of TCD4+ lymphocytes, exposure to HIV-1 and the time of the use of ART were 542.1 cells/mm3 (SD = 256.4), 6.3 years (SD = 2.9) and 5.0 years (SD = 2.5), respectively. Of all variables studied, only histopathological diagnosis showed a significant difference between groups (LWHIV: granuloma n = 11 (68.0%); cyst n = 5 (31.2%); HIV-: granuloma n = 15 (93.8%); cyst n = 1 (6.2%); p = 0.015). When comparing the expressions of the three inflammatory markers between the groups, no significant differences were seen. There was no difference in the expression of RANK, PTHrP and MMP-9 in primary chronic apical periodontitis lesions between PLWHIV under ART and HIV- individuals.

Neurocognitive functioning in MDR-TB patients with and without HIV in KwaZulu-Natal, South Africa.

Optimising medication adherence is one of the essential factors in reversing the tide of a TB-HIV syndemic in sub-Saharan Africa, especially South Africa. Impairment in key neurocognitive domains may impair patients' ability to maintain adherence to treatment, but the level of cognition and its relationship to HIV status has not been examined in individuals with drug-resistant TB. We therefore investigated performance on several key neurocognitive domains in relationship to HIV status in a multidrug-resistant tuberculosis patients (MDR-TB) sample. We enrolled microbiologically confirmed MDR-TB inpatients at a TB-specialist referral hospital in KwaZulu-Natal province, South Africa. We collected cross-sectional data on sociodemographic, clinical and neurocognitive function (e.g. attention, memory, executive functioning, language fluency, visual-spatial, eye-hand coordination). For the primary analysis, we excluded participants with major depressive episode/substance use disorder (MDE/SUD). We fitted adjusted Poisson regression models to explore the association between HIV and neurocognitive function. We enrolled 200 people with MDR-TB; 33 had MDE/SUD, and data of 167 were analysed (151 HIV+, 16 HIV-). The mean age of participants was 34.2years; the majority were female (83%), and 53% had not completed secondary school. There was evidence of impaired neurocognitive functioning across all domains in both HIV+/- study participants. Based on the regression analyses, individuals with co-infection (MDR-TB/HIV+), as well as those who had longer duration of hospital stays experienced significantly lower cognitive performance in several domains. Poor cognitive performance was significantly related to older age and lower educational attainment. The presence of major depression or substance use disorders did not influence the significance of the findings. Adults with MDR-TB have significant neurocognitive impairment, especially if HIV positive. An integrated approach is necessary in the management of MDR-TB as cognitive health influences the ability to adhere to chronic treatment, clinical outcomes and functionality.

Prediabetes among HIV-infected individuals receiving antiretroviral therapy: prevalence, diagnostic tests, and associated factors

BackgroundMetabolic complications in human immunodeficiency virus (HIV)-infected individuals are common. Prediabetes represents a high risk for future diabetes development. This study aimed to determine the prevalence, diagnostic methods, and associated factors of prediabetes among HIV-infected individuals receiving antiretroviral therapy (ART).MethodsA cross-sectional study was conducted among HIV-infected adults without a history of diabetes who were receiving ART. Fasting plasma glucose (FPG), 2-hour plasma glucose (2-h PG) after a 75-g oral glucose tolerance test, and hemoglobin A1c (HbA1c) were assessed.ResultsA total of 397 patients with a mean age of 47.0 ± 9.8 years and 55.7% male, were studied. All received ART with undetectable plasma viral load. The mean duration of ART was 9.6 ± 5.2 years, and the mean CD4 cell count was 554 ± 235 cells/mm3. Among the patients, 28 (7.1%) had first-diagnosed diabetes, and 133 (33.5%) patients had prediabetes. Glycemia estimation by FPG, 2-h PG, and HbA1c showed a prediabetes prevalence of 17.4%, 14.7%, and 12.5%, respectively. The kappa statistics for the agreement of FPG and 2-h PG, HbA1c and 2-h PG, and HbA1c and FPG were 0.317, 0.429, and 0.396, respectively. In multivariate analysis, hypertension [odds ratio (OR) 3.38; 95% confidence interval (CI), 1.16-9.91; p = 0.026), and triglycerides > 150 mg/dL (OR 2.11; 95% CI, 1.01-4.44; p = 0.047) were factors significantly associated with prediabetes.ConclusionsPrediabetes among HIV-infected individuals receiving ART is common. The agreements of glycemia estimation methods are minimal to weak. HbA1c may underestimate prediabetes prevalence. Using FPG together with HbA1c increases the detection rate to approximately three-quarters of prediabetes patients. HIV-infected individuals who had hypertension and hypertriglyceridemia should be regularly assessed for prediabetes.Trial registration ClinicalTrial.gov, NCT03545217. Registered 1 June 2018—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03545217

Is the use of the QPC cognitive complaints questionnaire relevant for the screening strategy of HIV-Associated neurocognitive disorders?

ABSTRACT Background: The screening strategy for HIV-Associated Neurocognitive Disorders (HAND) is challenging. The French Expert Report recommend the use of the Cognitive Complaints Questionnaire (QPC) and the Montreal Cognitive assessment. However, the QPC has never been studied in People Living with HIV (PLWH). This study aims to determine the degree of agreement between QPC and the presence of HAND according to Frascati criteria, established by a battery of neuropsychological tests. Methods: Data from patients who performed both a QPC and a battery of neuropsychological tests over a six-month follow-up period were evaluated retrospectively. Results: A total of 121 patients were selected, with a median age of 53.1 years old. Among participants, 92.6% had an undetectable plasma viral load, 49.6% had a nadir CD4 less than 200/mm3 and 23.1% had a CDC stage C. Median CD4 cell count was 686/mm3. Prevalence of HAND was 57%, including 28.9% of Asymptomatic Neurocognitive Impairment, 24.8% of Mild Neurocognitive Disorder and 3.3% of HIV-associated Dementia. This analyze shows no agreement between QPC and HIV-associated neurocognitive disorders (kappa = −0.007). Conclusions: The QPC is not relevant in the screening for HAND. Thus, it urges to develop a specific tool to assess cognitive complaints among PLWH.