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Introduction: HIV treating physicians in the Netherlands follow the guidelines of the Department of Health and Human Services (DHHS). Most of these recommended initial regimens are single-tablet regimens (STRs), which incur higher costs. By the end of 2017, generic NRTI backbones had become widely available, offering a potentially cheaper multi-tablet regimen. This study aimed to evaluate guideline compliance in people with HIV who started antiretroviral therapy (ART), the uptake of generic multi-tablet regimens (gMTRs), and associated medication costs. Methods: This retrospective cohort study used data from the Dutch HIV Monitoring Foundation to determine the proportion of treatment-naïve people entering care who initiated ART according to the DHHS and type of ART regimens prescribed between January 2016 and December 2020. We analyzed ART prescriptions, both at the national level and per individual HIV treatment centers. We calculated the monthly ART costs based on Dutch medicine prices listed on www.medicijnkosten.nl for each calendar year. Results: In 2016, an integrase inhibitor-containing regimen was initiated in 77.3% which increased to 87.8% in 2020. The compliance rate to DHHS-recommended initial regimens ranged from 82.8% in 2016 to 90.9% in 2020. Most patients received single-tablet regimens, 81.3% in 2016 to 60.3% in 2020. After the introduction the gMTRs showed a steady increase from 17.8% in 2018 to 37.8% in 2020. The cost of the first-line regimen per patient decreased by 22.9% in 2020 compared with 2017. The decrease was larger in centers where treatment-naïve individuals with HIV were preferentially initiated on a gMTR. Conclusions: There was a high compliance to the "DHHS-recommended initial regimens for most people with HIV" in the Netherlands. Most people who initiated ART received STRs, although the percentage of people who started on STRs gradually decreased over time. The use of gMTRs increased over time and was associated with lower medication costs. [ABSTRACT FROM AUTHOR]

Background Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use. Methods Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA–suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine. Cases were 1:2 matched to controls on triple-drug antiretroviral regimens by the use of dolutegravir-based regimens, age, sex, transmission route, CD4+ T-cell nadir, and HIV RNA zenith. The primary endpoint was the treatment failure rate in cases versus controls at 1 year by intention-to-treat and on-treatment analyses with 5% noninferiority margin. Results The 2040 participants were 680 cases and 1380 controls. Treatment failure in the 390 dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference: −3.78% [95% confidence interval {CI}, −7.49% to.08%]) by intention-to-treat and 1.39% and 0.80% (difference: 0.59% [95% CI, –.80% to 1.98%]) by on-treatment analyses. The treatment failure risk in 290 non-dolutegravir-based cases was also noninferior to controls. Antiretroviral regimen modifications unrelated to virological failure explained the higher treatment failure rate by intention-to-treat. A shorter time on triple-drug antiretroviral therapy and being of non-Western origin was associated with treatment failure. Treatment failure, defined as 2 consecutive HIV RNA >50 copies/mL, occurred in 4 cases and 5 controls but without genotypic resistance detected. Viral blips occured comparable in cases and controls but cases gained more weight, especially when tenofovir-based regimens were discontinued. Conclusions In routine care, dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral regimens after 1 year, supporting the use of dolutegravir/lamivudine in clinical practice. Clinical Trials Registration NCT04707326. [ABSTRACT FROM AUTHOR]

Background We determined the frequency of and factors associated with ≥10% weight gain and its metabolic effects in virally suppressed people with human immunodeficiency virus (PWH) from the Dutch national AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort switching to tenofovir alafenamide (TAF) and/or integrase strand transfer inhibitor (INSTI). Methods We identified antiretroviral therapy–experienced but TAF/INSTI-naive PWH who switched to a TAF and/or INSTI-containing regimen while virally suppressed for >12 months. Individuals with comorbidities/comedication associated with weight change were excluded. Analyses were stratified by switch to only TAF, only INSTI, or TAF + INSTI. Factors associated with ≥10% weight gain were assessed using parametric survival models. Changes in glucose, lipids, and blood pressure postswitch were modeled using mixed-effects linear regression and compared between those with and without ≥10% weight gain. Results Among 1544 PWH who switched to only TAF, 2629 to only INSTI, and 918 to combined TAF + INSTI, ≥10% weight gain was observed in 8.8%, 10.6%, and 14.4%, respectively. Across these groups, weight gain was more frequent in Western and sub-Saharan African females than Western males. Weight gain was also more frequent in those with weight loss ≥1 kg/year before switching, age <40 years, and those discontinuing efavirenz. In those with ≥10% weight gain, 53.7% remained in the same body mass index (BMI) category, while a BMI change from normal/overweight at baseline to obesity at 24 months postswitch was seen in 13.9%, 11.7%, and 15.2% of those switching to only TAF, only INSTI, and TAF + INSTI, respectively. PWH with ≥10% weight gain showed significantly larger, but small increases in glucose, blood pressure, and lipid levels. Lipid increases were limited to those whose switch included TAF, whereas lipids decreased after switching to only INSTI. Conclusions Weight gain of ≥10% after switch to TAF and/or INSTI was common in virally suppressed PWH, particularly in females and those starting both drugs simultaneously. Consequent changes in metabolic parameters were, however, modest. [ABSTRACT FROM AUTHOR]

Smoking may affect cardiovascular disease risk more strongly in human immunodeficiency virus (HIV)-infected individuals than HIV-uninfected individuals. We hypothesized that an interaction at the level of the immune system may contribute to this increased risk. We assessed soluble markers of inflammation (high-sensitivity C-reactive protein [hsCRP]), immune activation (soluble [s]CD14 and sCD163), and coagulation (D-dimer) in HIV-infected and uninfected never, former, and current smokers. Smoking was independently associated with higher hsCRP levels and lower sCD163 levels and was borderline significantly associated with higher sCD14 and D-dimer levels. We found no evidence of a differential effect of smoking in HIV-infected individuals as compared to uninfected individuals. [ABSTRACT FROM AUTHOR]

Background: Aging-associated noncommunicable comorbidities are more prevalent among human immunodeficiency virus type 1 (HIV)-infected individuals than among HIV-uninfected individuals. Residual HIV-related chronic immune activation and senescence may increase the risk of developing comorbidities.Methods: Immune phenotyping, thymic output, and telomere length were assessed in 94 HIV-infected individuals who were aged >45 years and receiving antiretroviral therapy (ART; cases) and 95 age-matched uninfected controls.Results: Cases had lower CD4(+) T-cell counts, higher CD8(+) T-cell counts, and increased levels of immune activation (ie, increased soluble CD14 [sCD14] level and increased percentages of CD38(+)HLA-DR(+) cells among both CD4(+) and CD8(+) T cells), regulatory T cells, and percentage of programmed cell death 1 (PD-1)-expressing cells among CD4(+) T cells. Immune senescence levels (ie, percentages of CD27(-)CD28(-) cells or CD57(+) cells) were comparable between cases and controls. Peripheral blood mononuclear cells from cases had shorter telomeres but increased single-joint T-cell receptor excision circle content and CD31(+) naive CD4(+) T cells. Although cytomegalovirus (CMV) antibody titers were higher in cases, CMV-specific T-cell responses were comparable between cases and controls. T-cell senescence in cases was independently associated with T-cell activation but not with CMV-specific immune responses.Conclusions: Despite long-term receipt of ART, HIV-infected adults had higher levels of immune activation, regulatory T cells, and PD-1-expressing CD4(+) cells and shorter telomeres. The increased soluble CD14 levels and percentage of CD38(+)HLA-DR(+) cells among CD4(+) T cells correlated with shorter telomeres and increased regulatory T-cell levels. This suggests that HIV influences immune function irreversibly, with several pathways that are persistently abnormal during effective ART. Therapies aimed at improving immune health during ART are needed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Human immunodeficiency virus (HIV) and combination antiretroviral therapy (cART) may both contribute to the higher prevalence of osteoporosis and osteopenia in HIV-infected individuals. METHODS: Using dual-energy X-ray absorptiometry, we compared lumbar spine, total hip, and femoral neck bone mineral density (BMD) in 581 HIV-positive (94.7% receiving cART) and 520 HIV-negative participants of the AGEhIV Cohort Study, aged >=45 years. We used multivariable linear regression to investigate independent associations between HIV, HIV disease characteristics, ART, and BMD. RESULTS: The study population largely consisted of men who have sex with men (MSM). Osteoporosis was significantly more prevalent in those with HIV infection (13.3% vs 6.7%; P < .001). After adjustment for body weight and smoking, being HIV-positive was no longer independently associated with BMD. Low body weight was more strongly negatively associated with BMD in HIV-positive persons with a history of a Centers for Disease Control and Prevention class B or C event. Interestingly, regardless of HIV status, younger MSM had significantly lower BMD than older MSM, heterosexual men, and women. CONCLUSIONS: The observed lower BMD in treated HIV-positive individuals was largely explained by both lower body weight and more smoking. Having experienced symptomatic HIV disease, often associated with weight loss, was another risk factor. The low BMD observed in younger MSM remains unexplained and needs further study. [ABSTRACT FROM AUTHOR]

Objectives HIV-exposed infants, including those who do not become infected, have higher morbidity and mortality rates than HIV unexposed infants. The underlying mechanisms of this difference are largely unknown. The objective of this study was to identify the risk factors for mortality among HIV-exposed (infected as well as uninfected) infants in a prevention of mother-to-child transmission ( PMTCT) programme in Cameroon. Methods We analysed the data from 319 mother-infant pairs included in a PMTCT programme at a rural and an urban hospital between 2004 and 2012. The programme offered free formula feeding, monthly follow-up visits and antiretroviral therapy ( ART) according to national PMTCT guidelines. Mother-infant pairs were divided in three study groups, based on year of recruitment and study site: (I) rural hospital, 2004-07; ( II) rural hospital, 2008-12; ( III) urban hospital, 2008-12. Results Two hundred and eighty-five medical records were included in the final analysis. Infant mortality rates were 23.9%, 20.0% and 5.3% in group I, II and III, respectively ( P = 0.02). Hazard ratios of infant mortality were 6.4 ( P < 0.001) for prematurity, 4.6 ( P = 0.04) for no maternal use of ARTs, 5.6 ( P = 0.025) for mixed feeding, 2.7 for home deliveries ( P = 0.087) and 0.4 ( P = 0.138) for urban study group. Conclusions In this programme, prematurity, no ART use, and the practice of mixed feeding were independent predictors of infant mortality. Mixed feeding and not using ART increased the hazard of death, probably through its increased risk of HIV infection. Although mortality rates were significantly higher in the rural area, rural setting was not a risk factor for infant mortality. These findings may contribute to the development of tailor-made programmes to reduce infant mortality rates among HIV-exposed infants. [ABSTRACT FROM AUTHOR]

Temporary cART during primary HIV-infection (PHI) did not select for drug resistance mutations after treatment interruption and did not affect the subsequent virological response to long-term cART. Our data demonstrate that fear of drug resistance development is not a valid argument to refrain from temporary early treatment during PHI. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) is the leading cause of adult mortality in low-income countries but data on the prevalence of cardiovascular risk factors such as hypertension are scarce, especially in sub-Saharan Africa (SSA). This study aims to assess the prevalence of hypertension and determinants of blood pressure in four SSA populations in rural Nigeria and Kenya, and urban Namibia and Tanzania. Methods and Findings: We performed four cross-sectional household surveys in Kwara State, Nigeria; Nandi district, Kenya; Dar es Salaam, Tanzania and Greater Windhoek, Namibia, between 2009-2011. Representative population-based samples were drawn in Nigeria and Namibia. The Kenya and Tanzania study populations consisted of specific target groups. Within a final sample size of 5,500 households, 9,857 non-pregnant adults were eligible for analysis on hypertension. Of those, 7,568 respondents ≥18 years were included. The primary outcome measure was the prevalence of hypertension in each of the populations under study. The age-standardized prevalence of hypertension was 19.3% (95%CI:17.3-21.3) in rural Nigeria, 21.4% (19.8-23.0) in rural Kenya, 23.7% (21.3-26.2) in urban Tanzania, and 38.0% (35.9-40.1) in urban Namibia. In individuals with hypertension, the proportion of grade 2 (≥160/100 mmHg) or grade 3 hypertension (≥180/110 mmHg) ranged from 29.2% (Namibia) to 43.3% (Nigeria). Control of hypertension ranged from 2.6% in Kenya to 17.8% in Namibia. Obesity prevalence (BMI ≥30) ranged from 6.1% (Nigeria) to 17.4% (Tanzania) and together with age and gender, BMI independently predicted blood pressure level in all study populations. Diabetes prevalence ranged from 2.1% (Namibia) to 3.7% (Tanzania). Conclusion: Hypertension was the most frequently observed risk factor for CVD in both urban and rural communities in SSA and will contribute to the growing burden of CVD in SSA. Low levels of control of hypertension are alarming. Strengthening of health care systems in SSA to contain the emerging epidemic of CVD is urgently needed. [ABSTRACT FROM AUTHOR]

Background. Recommendations that nevirapine (NVP) should be avoided in female individuals with CD4 cell counts >250 cells/μL and in male individuals with CD4 cell counts >400 cells/μL are based on findings in treatment-naive patients. It is unclear whether these guidelines also apply to treatment-experienced patients switching to NVP-based combination therapy. Methods. Patients in the ATHENA cohort study who had used NVP-based combination therapy were included. We identified patients who discontinued NVP-based combination therapy because of hypersensitivity reactions (HSRs; rash and/or hepatotoxicity) within 18 weeks after starting such therapy. We grouped patients according to their CD4 cell count at the start of NVP-based combination therapy (current CD4 cell count) as having a high CD4 cell count (for female patients, >250 cells/μL; for male patients, >400 cells/μL) or a low CD4 cell count. Treatment-experienced patients were further subdivided according to the last available CD4 cell count before first receipt of antiretroviral therapy (ART; pre-ART CD4 cell count) using the same criteria. Risk factors for HSR were assessed using multivariate logistic regression. Results. Of 3752 patients receiving NVP-based combination therapy, 231 patients (6.2%) discontinued NVP therapy because of HSRs. Independent risk factors included female sex and Asian ethnicity. Having an undetectable viral load (VL) at the start of NVP therapy was associated with reduced risk of developing an HSR (adjusted odds ratio [OR], 0.52; 95% confidence interval [CI], 0.38-0.71). Pretreated patients with low pre-ART and high current CD4 cell counts and a detectable VL when switching to NVP-based combination therapy had a significantly higher risk of developing an HSR, compared with treatment-naive patients who started NVP therapy with low CD4 cell counts (adjusted OR, 1.87; 95% CI, 1.11-3.12); pretreated patients with low pre-ART CD4 cell counts who switched to NVP therapy with a high current CD4 cell count and an undetectable VL did not have an increased risk of developing an HSR (adjusted OR, 1.03; 95% CI, 0.66-1.61). Conclusions. Treatment-experienced patients who start NVP-based combination therapy with low pre-ART and high current CD4 cell counts and an undetectable VL have a similar likelihood for discontinuing NVP therapy because of HSRs, compared with treatment-naive patients with low CD4 cell counts. This suggests that NVP-based combination therapy may be safely initiated in such patients. However, in similar patients with a detectable VL, it is prudent to continue to adhere to current CD4 cell count thresholds. [ABSTRACT FROM AUTHOR]

Background Long-term viral suppression on antiretroviral therapy (ART) is not established among all people with human immunodeficiency virus (PWH). Young adults (18–24 years) are recognized as a group vulnerable for suboptimal virological treatment outcomes. The aim of this study is to evaluate longitudinal virological treatment outcomes and to identify risk factors for virological failure (VF) among young adults with non-perinatally and perinatally acquired human immunodeficiency virus (HIV) in the Netherlands. Methods We included individuals registered in the national ATHENA observational cohort from 2000 until 2020 who had entered care before the age of 25 years, who had received ART for at least 6 months with at least 2 available HIV ribonucleic acid measurements between the age of 18 and 24 years. We compared VF between age groups 12–17, 18–24, and 25–30 years. A multivariable generalized linear mixed model was used to evaluate risk factors for VF. Analyses were stratified by HIV acquisition mode. Results In total, 1174 non-perinatally PWH and 157 perinatally PWH were included. In 2020, VF rate was 7% in non-perinatally PWH young adults and 19% in perinatally PWH young adults. The adjusted risk for VF was significantly higher in those aged 18–24 compared to 25–30 years in both non-perinatally PWH (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.07–1.50) and perinatally PWH (OR, 2.34; 95% CI, 1.48–3.71). Conclusions Young adulthood is a vulnerable period, with increased risk for VF, especially for perinatally PWH. The probability of VF decreased over time, but less for perinatally PWH compared to non-perinatally PWH. [ABSTRACT FROM AUTHOR]

Background Within the ongoing AGEhIV Cohort Study in Amsterdam, we prospectively compared the incidence of and risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection between human immunodeficiency virus (HIV)–positive and HIV-negative participants. Moreover, we compared SARS-CoV-2 nucleocapsid antibody levels between participants with incident infection from both groups. Methods Starting in September 2020, consenting HIV-positive and HIV-negative participants were assessed every 6 months for incident SARS-CoV-2 infection, using combined immunoglobulin (Ig) A/IgM/IgG SARS-CoV-2 nucleocapsid antibody assay. Cumulative incidence of SARS-CoV-2 infection and associated risk factors were assessed from 27 February 2020 through 30 April 2021, using complementary log-log regression. In those with incident SARS-CoV-2 infection, nucleocapsid (N) antibody levels were compared between groups using linear regression. Results The study included 241 HIV-positive (99.2% virally suppressed) and 326 HIV-negative AGEhIV participants. The cumulative SARS-CoV-2 incidence by April 2021 was 13.4% and 11.6% in HIV-positive and HIV-negative participants, respectively (P  = .61). Younger age and African origin were independently associated with incident infection. In those with incident infection, only self-reported fever, but not HIV status, was associated with higher N antibody levels. Conclusions HIV-positive individuals with suppressed viremia and adequate CD4 cell counts had similar risk of SARS-CoV-2 acquisition and similar SARS-CoV-2 N antibody levels after infection compared with a comparable HIV-negative cohort. Clinical Trial Registration NCT01466582. [ABSTRACT FROM AUTHOR]

Background Little is known about the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron infection in people with human immunodeficiency virus (HIV; PWH) with vaccine-induced or hybrid immunity. We assessed the incidence of Omicron infection in 209 AGEhIV coronavirus disease 2019 substudy participants with well-controlled HIV on antiretroviral therapy and 280 comparable controls, who had received at least the primary vaccination series. Methods From September 2020 onward, participants were assessed every 6 months for the incidence of SARS-CoV-2 infection, per SARS-CoV-2 nucleocapsid antibody assay or self-reported positive antigen or polymerase chain reaction test. Between 1 January and 31 October 2022, the cumulative incidence of Omicron infection and associated risk factors were estimated using a conditional risk-set Cox proportional hazards model. Results The cumulative incidence of a first Omicron infection was 58.3% by 31 October 2022, not significantly different between groups. HIV status was not independently associated with acquiring Omicron infection. Former and current smoking, as well as an increased predicted anti-spike immunoglobulin G titer were significantly associated with a lower risk of Omicron infection. The majority of infections were symptomatic, but none required hospitalization. Conclusions People with well-controlled HIV and controls in our cohort experienced a similarly high proportion of Omicron infections. More booster vaccinations significantly reduced the risk of infection. Clinical Trial Registration. NCT01466582 [ABSTRACT FROM AUTHOR]

Background Although people living with human immunodeficiency virus (PLWH) are at increased risk of invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP), it is unclear whether this remains the case in the setting of early initiation of combination antiretroviral therapy (cART), at high CD4 cell counts. This is important, as pneumococcal vaccination coverage in PLWH is low in Europe and the United States, despite longstanding international recommendations. Methods We identified all CAP and IPD cases between 2008 and 2017 in a cohort of PLWH in a Dutch HIV referral center. We calculated incidence rates stratified by CD4 count and cART status and conducted a case-control study to identify risk factors for CAP in PLWH receiving cART. Results Incidence rates of IPD and CAP in PLWH were 111 and 1529 per 100 000 patient-years of follow-up (PYFU). Although IPD and CAP occurred more frequently in patients with CD4 counts <500 cells/μL (incidence rate ratio [IRR], 6.1 [95% confidence interval, 2.2–17] and IRR, 2.4 [95% confidence interval, 1.9–3.0]), the incidence rate in patients with CD4 counts >500 cells/μL remained higher compared with the general population (946 vs 188 per 100 000 PYFU). All IPD isolates were vaccine serotypes. Risk factors for CAP were older age, CD4 counts <500 cells/μL, smoking, drug use, and chronic obstructive pulmonary disease. Conclusions The incidence of IPD and CAP among PLWH remains higher compared with the general population, even in those who are virally suppressed and have high CD4 counts. With all serotyped IPD isolates covered by pneumococcal vaccines, our study provides additional argumentation against the poor current adherence to international recommendations to vaccinate PLWH. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus (HIV)-infected individuals are at increased risk of chronic kidney disease (CKD). Human immunodeficiency virus infection, traditional CKD risk factors, and combination antiretroviral therapy (cART) may all contribute.Methods: We compared prevalence of renal impairment (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73m2), albuminuria (albumin/creatinine ratio ≥3 mg/mmol), and proximal renal tubular dysfunction (retinol-binding protein/creatinine ratio >2.93μg/mmol and/or fractional phosphate excretion >20% with plasma phosphate <0.8 mmol/L) in 596 HIV-infected and 544 HIV-uninfected AGEhIV Cohort Study participants. We also assessed whether being HIV-infected on cART, with follow-up censored when cART regimen was modified, was associated with greater eGFR decline or worsening albuminuria (increase ≥10%/year with change in albuminuria category).Results: Human immunodeficiency virus infection was independently associated with renal impairment (adjusted odds ratio [aOR] = 2.1; 95% confidence interval [CI] = 1.0-4.4), albuminuria (aOR = 5.8; 95% CI = 3.7-9.0), and proximal renal tubular dysfunction (aOR = 7.0; 95% CI = 4.9-10.2]). Among 377 HIV-infected and 479 HIV-uninfected individuals (median follow-up = 3.9/4.1 years, respectively) included in longitudinal analyses, being HIV-infected and remaining on unmodified cART was independently associated with greater eGFR decline (-0.56; 95% CI = -0.87 to -0.24 mL/min/1.73m2/year) and worsening albuminuria (aOR = 2.3; 95% CI = 1.3-4.0).Conclusions: In these middle-aged individuals, HIV infection was independently associated with renal impairment, albuminuria, and proximal renal tubular dysfunction. Human immunodeficiency virus-infected individuals on cART (predominantly containing tenofovir disoproxil fumarate) were also more likely to experience eGFR decline and worsening albuminuria compared with HIV-uninfected individuals. [ABSTRACT FROM AUTHOR]

Objectives: To provide an overview of the demographics, treatment characteristics and long-term outcomes of children with perinatal HIV-1 infection (PHIV) living in the Netherlands (NL) and to specifically investigate whether outcomes differ by children's adoption status. Design: A prospective population-based open cohort including children with PHIV in NL. Methods: We included children with PHIV who had entered HIV care in NL since 2007, in view of a sharp increase in the number of adopted children with PHIV since that year. We compared the proportion with virologic suppression and CD4+T-cell count over time between the following groups of children with PHIV: adopted and born outside NL, non-adopted born in NL, and non-adopted born outside NL, using generalized estimating equations and linear mixed effects models, respectively. To account for the variation in cohort inclusion, we analyzed data of children exposed to at least one year of antiretroviral therapy (ART). Results: We included 148 children (827.5 person-years of follow-up, 72% adopted, age at start care in NL 2.4 (0.5–5.3)). Under-18 mortality was zero. Over the years, a boosted PI-based regimen was most often prescribed. The use of integrase inhibitors increased since 2015. Non-adopted children born in NL were less likely to achieve virological suppression compared to adopted children (OR 0.66, 95%CI 0.51–0.86, p = 0.001), which disappeared after excluding one child with suspected treatment nonadherence (OR 0.85, 95%CI 0.57–1.25, p = 0.400). CD4+T-cell Z-score trajectories were not significantly different between groups. Conclusions: Despite considerable and increasing diversity of the population of children with PHIV in NL, geographical origin and adoption status do not seem to pose important challenges in achieving good immunological and virological outcomes. [ABSTRACT FROM AUTHOR]

Background: Patients with HIV, even with suppressed viremia on combination antiretroviral therapy, are at increased risk for cardiovascular disease. The underlying pathophysiology remains to be clarified. Aortic stiffness, known to be associated with cardiovascular disease in the general population, was investigated in a cohort of HIV type 1 (HIV 1)-infected and similar but uninfected individuals. Methods: Aortic stiffness was assessed by measuring pulse wave velocity (PWV) with an Arteriograph. Five hundred seven HIVuninfected and 566 HIV 1-infected individuals, predominantly with suppressed viremia on combination antiretroviral therapy, aged &≤8805;45 years, participating in the ongoing AGEhIV Cohort Study were included in the analysis. Multivariable linear regression was used to investigate whether HIV was independently associated with aortic stiffness, adjusting for traditional cardiovascular risk factors. Results: Study groups were comparable in demographics; smoking and hypertension were more prevalent in HIV-infected participants. PWV was higher in the HIV-infected group (7.9 vs. 7.7 m/s, P = 0.004). After adjustment for mean arterial pressure, age, gender, and smoking, HIV status was not significantly associated with aortic stiffness. In HIV-infected participants, having a nadir CD4+ T-cell count ≤100 cells per cubic millimeter was independently associated with a higher PWV. Conclusions: The increased aortic stiffness in HIV-infected participants was largely explained by a higher prevalence of traditional cardiovascular risk factors, particularly smoking. Although HIV itself was not independently associated with higher aortic stiffness, a prior greater degree of immunodeficiency was. This suggests a detrimental effect of immunodeficiency on the aortic wall, possibly mediated by inflammation. [ABSTRACT FROM AUTHOR]

A high prevalence of low bone mineral density (BMD) has been reported among men with primary or chronic human immunodeficiency virus (HIV) infection. To gain further insight into the contribution of HIV infection, we compared the BMD of 41 men who have sex with men (MSM) with primary HIV infection, 106 MSM with chronic HIV infection, and a control group of 30 MSM without HIV infection. Low BMD, defined as a z score of ≥2.0 SDs below the mean at the lumbar spine or hip, was highly prevalent in all 3 groups. In the multivariate analyses, HIV infection was not associated with BMD, suggesting that low BMD previously reported in HIV-infected MSM may predate HIV acquisition. [ABSTRACT FROM PUBLISHER]

Background: The objective of this study was to assess the benefit of temporary combination antiretroviral therapy (cART) during primary HIV infection (PHI). Methods and Findings: Adult patients with laboratory evidence of PHI were recruited in 13 HIV treatment centers in the Netherlands and randomly assigned to receive no treatment or 24 or 60 wk of cART (allocation in a 1:1:1 ratio); if therapy was clinically indicated, participants were randomized over the two treatment arms (allocation in a 1:1 ratio). Primary end points were (1) viral set point, defined as the plasma viral load 36 wk after randomization in the no treatment arm and 36 wk after treatment interruption in the treatment arms, and (2) the total time that patients were off therapy, defined as the time between randomization and start of cART in the no treatment arm, and the time between treatment interruption and restart of cART in the treatment arms. cART was (re)started in case of confirmed CD4 cell count <350 cells/mm³ or symptomatic HIV disease. In total, 173 participants were randomized. The modified intention-to-treat analysis comprised 168 patients: 115 were randomized over the three study arms, and 53 randomized over the two treatment arms. Of the 115 patients randomized over the three study arms, mean viral set point was 4.8 (standard deviation 0.6) log10 copies/ml in the no treatment arm, and 4.0 (1.0) and 4.3 (0.9) log10 copies/ml in the 24- and 60-wk treatment arms (between groups: p<0.001). The median total time off therapy in the no treatment arm was 0.7 (95% CI 0.0-1.8) y compared to 3.0 (1.9-4.2) and 1.8 (0.5-3.0) y in the 24- and 60-wk treatment arms (log rank test, p<0.001). In the adjusted Cox analysis, both 24 wk (hazard ratio 0.42 [95% CI 0.25-0.73]) and 60 wk of early treatment (hazard ratio 0.55 [0.32-0.95]) were associated with time to (re)start of cART. Conclusions: In this trial, temporary cART during PHI was found to transiently lower the viral set point and defer the restart of cART during chronic HIV infection. [ABSTRACT FROM AUTHOR]

Plasma nelfinavir concentration ratios (CRs) were calculated for all pregnant (n = 27) and nonpregnant (n = 48) human immunodeficiency virus type 1-infected women receiving the drug who visited our outpatient clinic. In pregnant women, mean and median nelfinavir CRs were significantly lower (P = .02 and P = .04, respectively), and 51% of the CRs were below the clinically relevant threshold of 0.90, compared with 35% of the CRs in nonpregnant women. After we adjusted for confounders, we found that the mean nelfinavir CR was 34% lower in pregnant women (P = .02). With targeted interventions, subsequent CRs in pregnant women showed a significant increase (median increase, 0.31; P = .01). [ABSTRACT FROM AUTHOR]

Cerebral white matter hyperintensities (WMH) persist in children and adults living with HIV, despite effective combination antiretroviral therapy (cART). As age and principal routes of transmission differ between children (perinatally) and adults (behaviorally), comparing the characteristics and determinants of WMH between these populations may increase our understanding of the pathophysiology of WMH. From separate cohorts of 31 children (NOVICE) and 74 adults (AGEhIV), we cross-sectionally assessed total WMH volume and number of WMH per location (periventricular vs. deep) using fluid-attenuated inversion recovery (FLAIR) MRI images. WMH were either periventricular when within 10mm of the lateral ventricles, or deep otherwise. We assessed patient- or HIV-related determinants of total WMH volume (adjusted for intracranial volume) and location of WMH using logistic regression, while stratifying on children and adults. At enrollment, median age of participants was 13.8 years (IQR 11.4–15.9) for children and 53.4 years (IQR 48.3–60.8) for adults and 27/31 children (87%) and 74/74 adults (100%) had an HIV RNA viral load <200 copies/mL. WMH were present in 16/27 (52%) children and 74/74 adults (100%). The prevalence of deep WMH was not different between groups, (16/16 [100%] in children vs. 71/74 [96%] in adults, p = 0,999), yet periventricular WMH were more prevalent in adults (74/74 [100%]) compared to children (9/16; 56%) (p<0.001). Median WMH volume was higher in adults compared to children (1182 mm3 [425–2617] vs. 109 mm3 [61.7–625], p<0.001). In children, boys were more likely to have deep WMH compared to girls. In adults, older age was associated with higher total WMH volume, and age, hypertension and lower CD4+ T-lymphocyte nadir with a higher number of periventricular WMH. Our findings suggest that the location of WMH differs between children and adults living with HIV, hinting at a different underlying pathogenesis. [ABSTRACT FROM AUTHOR]

Background A cross-sectional analysis of the Neurological, cOgnitive and VIsual performance in hiv-infected Children cohort showed significant cognitive impairment in combination antiretroviral therapy (cART)-treated, perinatally human immunodeficiency virus (HIV)-infected adolescents (PHIV+) compared to age-, sex-, ethnicity- and socioeconomic status (SES)-matched HIV-negative controls (HIV−). In this longitudinal study, we compared cognitive development in the same adolescents over time. Methods We repeated the standardized cognitive test battery after a mean of 4.6 years (standard deviation 0.3). In participants who completed both assessments, we compared cognitive trajectories between groups in the domains of intelligence quotient (IQ), processing speed, working memory, executive functioning, learning ability, and visual-motor function, using linear mixed models. We explored associations with disease- and treatment-related factors and used multivariate normative comparison (MNC) to determine the prevalence of cognitive impairment. Results There were 21 PHIV+ and 23 HIV− participants that completed 2 assessments and were similar concerning age, sex, ethnicity, and SES. Compared to HIV− participants, in PHIV+ participants the IQ score increased significantly more over time (group*time 6.01, 95% confidence interval [CI] 1.5–10.50; P =.012), whereas executive functioning decreased significantly more (group*time −1.43 z score, 95% CI −2.12 to −0.75; P <.001), resulting in the disappearance and appearance of significant differences. Processing speed, working memory, learning ability, and visual-motor function trajectories were not statistically different between groups. Univariately, those who had started cART at an older age deviated more in executive functioning (−0.13 z score, 95% CI −0.24 to −0.02; P =.043). The prevalence of cognitive impairments by MNC was similar in both groups, at both time points. Conclusions The cART-treated PHIV+ adolescents appeared to have similar global cognitive development, compared to their healthy peers. Executive functioning trajectory appears to deviate, potentially explained by earlier brain damage. [ABSTRACT FROM AUTHOR]

Evidence-based guidelines in HIV care aim to improve patients' health outcomes, quality of care, and cost-effectiveness. Laboratory monitoring plays an important role in assessing clinical status of patients and forms an integral part of HIV treatment guidelines. The Dutch HIV monitoring foundation (Stichting HIV Monitoring) previously observed variation between HIV treatment centres in the Netherlands in terms of compliance with guidelines for performing laboratory tests. Drawing on qualitative research methods, this article aims to describe factors that influence guideline compliance for laboratory monitoring in outpatient HIV care in the Netherlands. Twelve semi-structured in-depth interviews were conducted with a convenience sample of physicians from four HIV treatment centres. In general, physicians perceived laboratory guidelines as useful. However, unclear online visual representation of the guidelines, a lack of set reminders for tests, and assessment of patients' risk behaviour, which differs per patient, were identified as barriers to guideline compliance. The compartmentalisation of the Dutch healthcare system was viewed as hampering guideline compliance. A clinical-decision-support tool could possibly facilitate compliance with laboratory monitoring guidelines. Moreover, better alignment of HIV outpatient care, municipal health services and primary care, in terms of laboratory testing, could optimize efficiency, increase cost-effectiveness, and improve quality of HIV care. [ABSTRACT FROM AUTHOR]

Background. Despite successful antiretroviral therapy, people living with human immunodeficiency virus (PLWH) experience higher rates of age-related morbidity, including abnormal brain structure, brain function, and cognitive impairment. This has raised concerns that PLWH may experience accelerated aging-related brain pathology. Methods. We performed a multicenter longitudinal study of 134 virologically suppressed PLWH (median age, 56.0 years) and 79 demographically similar human immunodeficiency virus (HlV)-negative controls (median age, 57.2 years). To measure cognitive performance and brain pathology, we conducted detailed neuropsychological assessments and multimodality neuroimaging (T1-weighted, T2-weighted, diffusion magnetic resonance imaging [MRI], resting-state functional MRI, spectroscopy, arterial spin labeling) at baseline and at 2 years. Group differences in rates of change were assessed using linear mixed effects models. Results. One hundred twenty-three PLWH and 78 HIV-negative controls completed longitudinal assessments (median interval, 1.97 years). There were no differences between PLWH and HIV-negative controls in age, sex, years of education, smoking or alcohol use. At baseline, PLWH had poorer global cognitive performance (P < .01), lower gray matter volume (P = .04), higher white matter hyperintensity load (P = .02), abnormal white matter microstructure (P < .005), and greater brain-predicted age difference (P = .01). Longitudinally, there were no significant differences in rates of change in any neuroimaging measure between PLWH and HIV-negative controls (P > .1). Cognitive performance was longitudinally stable in both groups. Conclusions. We found no evidence that middle-aged PLWH, when receiving successful treatment, are at increased risk of accelerated aging-related brain changes or cognitive decline over 2 years. [ABSTRACT FROM AUTHOR]

Background: Paediatric data on CNS penetration of antiretroviral drugs are scarce.Objectives: To evaluate CNS penetration of antiretroviral drugs in HIV-infected children and explore associations with neurocognitive function.Patients and methods: Antiretroviral drug levels were measured in paired CSF and blood samples of clinically stable HIV-infected children between 8 and 18 years old on long-term combined ART. Plasma drug concentrations were corrected for protein binding. We evaluated CNS penetration using CSF/plasma ratios and compared CSF concentrations with the IC50 as a surrogate marker for effectiveness. Blood-brain barrier permeability was assessed for possible confounding. Associations with neurocognitive function were explored using linear regression analysis.Results: Median CSF/plasma ratios (IQR) were: lopinavir 0.059 (0.024-0.157, n = 7), efavirenz 0.681 (0.555-0.819, n = 12), tenofovir 0.021 (0.020-0.024, n = 4), lamivudine 0.464 (0.331-0.607, n = 17), emtricitabine 0.365 (0.343-0.435, n = 3), nevirapine 1.203 (n = 1), zidovudine 0.718 (0.711-1.227, n = 5) and abacavir 1.344 (0.670-2.450, n = 10). CSF concentrations were below the IC50 for tenofovir (100%), emtricitabine (100%), abacavir (50%) and zidovudine (17%). Lamivudine, lopinavir, efavirenz and nevirapine concentrations were all above the IC50. All participants were virologically suppressed in blood and CSF. CSF drug concentrations were not associated with blood-brain barrier permeability or neurocognitive function.Conclusions: We showed adequate CSF concentrations of lamivudine, lopinavir, efavirenz and nevirapine, and potential suboptimal CSF concentrations of tenofovir, abacavir and emtricitabine in long-term treated HIV-infected children. None the less, the use of combined antiretroviral drugs led to adequate viral suppression. [ABSTRACT FROM AUTHOR]

Background. Long-term comorbidities such as cognitive impairment remain prevalent in otherwise effectively treated people living with human immunodeficiency virus (HIV). We investigate the relationship between cognitive impairment and brain structure in successfully treated patients using multimodal neuroimaging from the Comorbidity in Relation to AIDS (COBRA) cohort. Methods. Cognitive function, brain tissue volumes, and white matter microstructure were assessed in 134 HIV-infected patients and 79 controls. All patients had suppressed plasma HIV RNA at cohort entry. In addition to comprehensive voxelwise analyses of volumetric and diffusion tensor imaging, we used an unsupervised machine learning approach to combine cognitive, diffusion, and volumetric data, taking advantage of the complementary information they provide. Results. Compared to the highly comparable control group, cognitive function was impaired in 4 of the 6 cognitive domains tested (median global T-scores: 50.8 vs 54.2; P < .001). Patients had lower gray but not white matter volumes, observed principally in regions where structure generally did not correlate with cognitive function. Widespread abnormalities in white matter microstructure were also seen, including reduced fractional anisotropy with increased mean and radial diffusivity. In contrast to the gray matter, these diffusion abnormalities correlated with cognitive function. Multivariate neuroimaging analysis identified a neuroimaging phenotype associated with poorer cognitive function, HIV infection, and systemic immune activation. Conclusions. Cognitive impairment, lower gray matter volume, and white matter microstructural abnormalities were evident in HIV-infected individuals despite fully suppressive antiretroviral therapy. White matter abnormalities appear to be a particularly important determinant of cognitive dysfunction seen in well-treated HIV-infected individuals. [ABSTRACT FROM AUTHOR]

Background. As a result of effective combination antiretroviral therapy (cART) and advanced supportive healthcare, a growing number of human immunodeficiency virus (HIV)-infected children survive into adulthood. The period of transition to adult care is often associated with impaired adherence to treatment and discontinuity of care. We aimed to evaluate virological and social outcomes of HIV-infected adolescents and young adults (AYAs) before and after transition, and explore which factors are associated with virological failure. Methods. We included 59 HIV-infected AYAs from the Netherlands who had entered into pediatric care and transitioned from pediatric to adult healthcare. We used HIV RNA load and cART data from the Dutch Stichting HIV Monitoring database (1996–2014), and collected social and treatment data from patients' medical records from all Dutch pediatric HIV treatment centers and 14 Dutch adult treatment centers involved. We evaluated risk factors for virological failure (VF) in a logistic regression model adjusted for repeated measurements. Results. HIV VF occurred frequently during the study period (14%-36%). During the transition period (from 18 to 19 years of age) there was a significant increase in VF compared with the reference group of children aged 12-13 years (odds ratio, 4.26 [95% confidence interval, 1.12-16.28]; P = .03). Characteristics significantly associated with VF were low educational attainment and lack of autonomy regarding medication adherence at transition. Conclusions. HIV-infected AYAs are vulnerable to VF, especially during the transition period. Identification of HIV-infected adolescents at high risk for VF might help to improve treatment success in this group. [ABSTRACT FROM AUTHOR]

The article describes the implementation of an antiretroviral access program for HIV-1 infected individuals in resource-limited settings to assess the effectiveness of highly active antiretroviral therapy (HAART). The results indicate that overall virologic and immunologic responses to HAART in resource-limited African settings can be as good as in Western settings.

Cites a study from the U.S. which found a similar rate of initial decline of plasma HIV-1 RNA (pVL) for antiretroviral drugs Nevirapine, Efavirenz and its combination after adjusting for baseline pVL and region. Reasons to assess the rate of pVL decline; Relation between high viral decay constant and virological failure.