Similar Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Similar Nucleocapsid Antibody Levels in People With Well-Controlled Human Immunodeficiency Virus (HIV) and a Comparable Cohort of People Without HIV.

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.

Neurocognitive Development in Perinatally Human Immunodeficiency Virus-infected Adolescents on Long-term Treatment, Compared to Healthy Matched Controls: A Longitudinal Study.

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.

Incidence and Risk Factors for Invasive Pneumococcal Disease and Community-acquired Pneumonia in Human Immunodeficiency Virus-Infected Individuals in a High-income Setting.

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.

Cause-specific mortality after diagnosis of cancer among HIV-positive patients: A collaborative analysis of cohort studies.

People living with HIV (PLHIV) are more likely than the general population to develop AIDS-defining malignancies (ADMs) and several non-ADMs (NADMs). Information is lacking on survival outcomes and cause-specific mortality after cancer diagnosis among PLHIV. We investigated causes of death within 5 years of cancer diagnosis in PLHIV enrolled in European and North American HIV cohorts starting antiretroviral therapy (ART) 1996-2015, aged ≥16 years, and subsequently diagnosed with cancer. Cancers were grouped: ADMs, viral NADMs and nonviral NADMs. We calculated cause-specific mortality rates (MR) after diagnosis of specific cancers and compared 5-year survival with the UK and France general populations. Among 83,856 PLHIV there were 4,436 cancer diagnoses. Of 603 deaths after ADM diagnosis, 292 (48%) were due to an ADM. There were 467/847 (55%) and 74/189 (39%) deaths that were due to an NADM after nonviral and viral NADM diagnoses, respectively. MR were higher for diagnoses between 1996 and 2005 versus 2006-2015: ADMs 102 (95% CI 92-113) per 1,000 years versus 88 (78-100), viral NADMs 134 (106-169) versus 111 (93-133) and nonviral NADMs 264 (232-300) versus 226 (206-248). Estimated 5-year survival for PLHIV diagnosed with liver (29% [19-39%]), lung (18% [13-23%]) and cervical (75% [63-84%]) cancer was similar to general populations. Survival after Hodgkin's lymphoma diagnosis was lower in PLHIV (75% [67-81%]). Among ART-treated PLHIV diagnosed with cancer, MR and causes of death varied by cancer type, with mortality highest for liver and lung cancers. Deaths within 5 years of NADM diagnoses were more likely to be from cancer than AIDS.

Compliance with laboratory monitoring guidelines in outpatient HIV care: a qualitative study in the Netherlands.

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.

No Evidence for Accelerated Aging-Related Brain Pathology in Treated Human Immunodeficiency Virus: Longitudinal Neuroimaging Results From the Comorbidity in Relation to AIDS (COBRA) Project.

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 (HIV)-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.

CNS penetration of ART in HIV-infected children.

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.

Higher Prevalence and Faster Progression of Chronic Kidney Disease in Human Immunodeficiency Virus-Infected Middle-Aged Individuals Compared With Human Immunodeficiency Virus-Uninfected Controls.

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.

Gray and White Matter Abnormalities in Treated Human Immunodeficiency Virus Disease and Their Relationship to Cognitive Function.

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.

Cigarette Smoking and Inflammation, Monocyte Activation, and Coagulation in HIV-Infected Individuals Receiving Antiretroviral Therapy, Compared With Uninfected Individuals.

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.

T-Cell Activation Independently Associates With Immune Senescence in HIV-Infected Recipients of Long-term Antiretroviral Treatment.

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.

Virological and Social Outcomes of HIV-Infected Adolescents and Young Adults in The Netherlands Before and After Transition to Adult Care.

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.

Low bone mineral density in patients with well-suppressed HIV infection: association with body weight, smoking, and prior advanced HIV disease.

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.

The impact of hormonal contraception and pregnancy on sexually transmitted infections and on cervicovaginal microbiota in african sex workers.

BACKGROUND: The observed association between Depo-Provera injectable use and increased HIV acquisition may be caused by hormone-induced increased susceptibility to other sexually transmitted infections (STIs) or changes in the cervicovaginal microbiota (VMB), accompanied by genital immune activation and/or mucosal remodeling. METHODS: Rwandan female sex workers (n = 800) were interviewed about contraceptive use and sexual behavior and were tested for STIs, bacterial vaginosis by Nugent score and pregnancy, at baseline. A subset of 397 HIV-negative, nonpregnant women were interviewed and tested again at regular intervals for 2 years. The VMB of a subset of 174 women was characterized by phylogenetic microarray. Outcomes of STI and VMB were compared between women with hormonal exposures (reporting oral contraceptive or injectable use, or testing positive for pregnancy) and controls (not reporting hormonal contraception and not pregnant). RESULTS: Oral contraceptive use was associated with increased human papillomavirus prevalence (adjusted odds ratio [aOR], 3.10; 1.21-7.94) and Chlamydia trachomatis incidence (aOR, 6.13; 1.58-23.80), injectable use with increased herpes simplex virus-2 prevalence (aOR, 2.13; 1.26-3.59) and pregnancy with lower HIV prevalence (aOR, 0.45; 0.22-0.92) but higher candidiasis incidence (aOR, 2.14; 1.12-4.09). Hormonal status was not associated with Nugent score category or phylogenetic VMB clustering, but oral contraceptive users had lower semiquantitative vaginal abundance of Prevotella, Sneathia/Leptotrichia amnionii, and Mycoplasma species. CONCLUSIONS: Oral contraceptive and injectable use were associated with several STIs but not with VMB composition. The increased herpes simplex virus-2 prevalence among injectable users might explain the potentially higher HIV risk in these women, but more research is needed to confirm these results and elucidate biological mechanisms.

Mortality risk factors among HIV-exposed infants in rural and urban Cameroon.

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.

Low bone mineral density, regardless of HIV status, in men who have sex with men.

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.

Screening for tuberculosis infection and effectiveness of preventive treatment among people with HIV in low-incidence settings.

OBJECTIVE: To determine the yield of screening for latent tuberculosis infection (LTBI) among people with HIV (PWH) in low tuberculosis (TB) incidence countries (<10 TB cases per 100 000 persons). DESIGN: A systematic review and meta-analysis were performed to assess prevalence and predictive factors of LTBI, rate of TB progression, effect of TB preventive treatment (TPT), and numbers needed to screen (NNS). METHODS: PubMed and Cochrane Library were searched for studies reporting primary data, excluding studies on active or paediatric TB. We extracted LTBI cases, odds ratios, and TB incidences; pooled estimates using a random-effects model; and used the Newcastle-Ottawa scale for bias. RESULTS: In 51 studies with 65 930 PWH, 12% [95% confidence interval (CI) 10-14] had a positive LTBI test, which was strongly associated with origin from a TB-endemic country [odds ratio (OR) 4.7] and exposure to TB (OR 2.9). Without TPT (10 629 PWH), TB incidence was 28/1000 person-years (PY; 95% CI 12-45) for LTBI-test positive versus 4/1000 PY (95% CI 0-7) for LTBI-test-negative individuals. Among 625 PWH (1644 PY) receiving TPT, 15 developed TB (6/1000 PY). An estimated 20 LTBI-positive individuals would need TPT to prevent one case of TB, and numbers NNS to detect LTBI or prevent active TB varied according to a-priori risk of LTBI. CONCLUSION: The relatively high prevalence of LTBI among PWH and the strong correlation with origin from a TB-endemic country support risk-stratified LTBI screening strategies for PWH in low-incidence countries and treating those who test positive.

COVID-19 epidemiology and performance of the WHO clinical algorithm to diagnose COVID-19 in people with HIV from Ukraine.

BACKGROUND: The two main objectives were to evaluate the COVID-19 point prevalence and the test performance of the WHO case definition to diagnose COVID-19 clinically in people with HIV in West Ukraine. METHODS: Multicenter cross-sectional study in Lviv, Ukraine, from October 2020-November 2021. COVID-19 unvaccinated people with HIV were included regardless of COVID-19 symptoms at routine clinical visits and had standardized medical, quality of life (EQ(5D)) and SARS-CoV-2 serology assessments. Reported symptoms indicating potential COVID-19 events at inclusion or between March 2020 and inclusion were classified by the WHO case definition as suspected, probable or confirmed. A clinical COVID-19 case was defined as being SARS-CoV-2 seropositive with at least a suspected COVID-19 according to the WHO case definition. The primary endpoints were the clinical COVID-19 prevalence and the test characteristics of the WHO case definition with SARS-CoV-2 serology as reference. (Clinicaltrials.gov:NCT04711954). RESULTS: The 971 included people with HIV were median 40 years, 38.8% women, 44.8% had prior AIDS, and 55.6% had comorbidities. SARS-CoV-2 seroprevalence was 40.1% (95%CI:37.0-43.1) and 20.5% (95%CI:18.0-23.1) had clinical COVID-19 median 4 months (IQR:2-7) before inclusion. Clinical COVID-19 occurred less frequently in people with HIV with tuberculosis history, injecting drug use, CD4+ T-cells <200/mL and unemployment. The quality of life was not impacted after COVID-19. An at least probable COVID-19 classification by the WHO case definition had 44.1% sensitivity (95%CI:38.7-49.7), 85.2% specificity (95%CI:81.5-88.4), 66.6% positive predictive value (95%CI:59.8-73.0) and 69.5% negative predictive value (95%CI:65.5-73.3) to diagnose COVID-19. CONCLUSIONS: COVID-19 unvaccinated people with HIV from Ukraine had a significant COVID-19 rate and using the WHO case definition had insufficient diagnostic accuracy to diagnose these cases. The lower burden in vulnerable people with HIV was unexpected but might reflect a shielding effect.

Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus: DUALING Prospective Nationwide Matched Cohort Study.

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.

No evidence of rapid reversibility of tenofovir alafenamide and/or integrase strand transfer inhibitor-associated weight gain.

OBJECTIVE: We aimed to determine the reversibility of at least 7% weight gain within 12 months following tenofovir alafenamide (TAF) and/or integrase strand transfer inhibitor (INSTI) discontinuation in people with HIV (PWH) from the Dutch ATHENA cohort. DESIGN AND METHODS: PWH with at least 7% weight gain within 24 months after first switch to TAF and/or INSTI whilst being virally suppressed were selected, excluding those with comorbidities/co-medication known to be associated with weight gain. PWH who discontinued only TAF, only INSTI or TAF+INSTI, with available follow-up weight, were included. Mean weight change in the 24 months prior to and 12 months after discontinuation was modelled using mixed-effects linear regression. Factors associated with yearly weight change were assessed using linear regression. RESULTS: In 115 PWH, discontinuing only TAF ( n  = 39), only INSTI ( n  = 53) or TAF+INSTI ( n  = 23), the adjusted mean modelled weight change in the 24 months prior to discontinuation was +4.50 kg [95% confidence interval (CI) 3.04-6.10], +4.80 kg (95% CI 2.43-7.03) and +4.13 kg (95% CI 1.50-7.13), respectively, and -1.89 kg (95% CI -3.40 to -0.37), -1.93 kg (95% CI -3.92 to +0.07) and -2.55 kg (95% CI -5.80 to +0.02) in the 12 months postdiscontinuation. A greater number of years since HIV diagnosis was associated with greater reversibility of weight gain. No associations were found between weight change postdiscontinuation and changes in NRTI backbone or anchor agent at moment of discontinuation. CONCLUSION: There was no evidence of rapid reversibility of at least 7% TAF-associated and/or INSTI-associated weight gain after discontinuation of these agents. Studies of larger and more diverse populations of PWH are required to more fully understand the degree to which weight gain is reversible when discontinuing TAF and/or INSTI.