Prevalence of detectable HIV-DNA and -RNA in cerebrospinal fluid of youth with perinatal HIV and impaired cognition on antiretroviral therapy.

OBJECTIVE: Central nervous system (CNS) HIV infection can impact cognition and may be an obstacle to cure in adolescents and young adults with perinatal HIV (AYAPHIV). IMPAACT2015 enrolled AYAPHIV on suppressive antiretroviral therapy (ART) with cognitive impairment to detect and quantify HIV in blood and cerebrospinal fluid (CSF). DESIGN: IMPAACT2015 was a U.S.-based multi-site, exploratory, observational study. METHODS: Cognitive impairment was defined as NIH Toolbox Fluid Cognition Composite score (FCCS) > 1 standard deviation below age-adjusted normative group mean. Cell-free HIV-RNA and cell-associated HIV pol/gag -DNA and 10 biomarkers of inflammation/neuronal injury were measured in paired CSF and blood. ART exposure concentrations were quantified in hair. RESULTS: Among 24 participants, 20 had successful CSF collection and 18 also met viral suppression criteria. 9/18 (50%) were female sex-at-birth, 14/18 (78%) were Black. Median (range) age was 20 years (13-27), time on ART 18.3 years (8.0-25.5), and FCCS 68 (53-80). HIV-DNA was detected in PBMCs from all participants. In CSF, 2/18 (11%, 95% CI: 1.4-34.7%) participants had detectable cell-free HIV-RNA, while HIV gag or pol -DNA was detectable in 13/18 (72%, 95% CI: 47-90%). Detectable HIV-DNA in CSF was associated with male sex-at-birth (p = 0.051), lower CD4 count at enrollment (p = 0.016), and higher PBMC HIV pol -DNA copies (p = 0.058). Hair antiretroviral concentrations and biomarkers were not associated with CSF HIV-DNA detection. CONCLUSIONS: We found a high proportion of AYAPHIV with neurocognitive impairment had CSF cells harboring HIV-DNA during long-term virologic suppression. This evidence of persistent HIV-DNA in CSF suggests that the CNS should be considered in treatment and cure studies.

Acceptability and tolerability of long-acting injectable cabotegravir or rilpivirine in the first cohort of virologically suppressed adolescents living with HIV (IMPAACT 2017/MOCHA): a secondary analysis of a phase 1/2, multicentre, open-label, non-comparative dose-finding study.

BACKGROUND: Long-acting injectable cabotegravir and rilpivirine have demonstrated safety, acceptability, and efficacy in adults living with HIV-1. The IMPAACT 2017 study (MOCHA study) was the first to use these injectable formulations in adolescents (aged 12-17 years) living with HIV-1. Herein, we report acceptability and tolerability outcomes in cohort 1 of the study. METHODS: In this a secondary analysis of a phase 1/2, multicentre, open-label, non-comparative dose-finding study, with continuation of pre-study oral combination antiretroviral treatment (ART), 55 adolescents living with HIV-1 were enrolled to receive sequential doses of either long-acting cabotegravir or rilpivirine and 52 received at least two injections. Participants had a body weight greater than 35 kg and BMI less than 31·5 kg/m2 and had been on stable ART for at least 90 consecutive days with an HIV-1 viral load of less than 50 copies per mL at a participating IMPAACT study site. Participants had to be willing to continue their pre-study ART during cohort 1. The primary objectives of the study were to confirm doses for oral and injectable cabotegravir and for injectable rilpivirine in adolescents living with HIV. This analysis of participant-reported outcomes included a face scale assessment of pain at each injection and a Pediatric Quality of Life Inventory (PedsQL) at baseline and week 16 for participants in the USA, South Africa, Botswana, and Thailand. A subset of 11 adolescents and 11 parents or caregivers in the USA underwent in-depth interviews after receipt of one or two injections. This trial is registered at ClinicalTrials.gov, NCT03497676. FINDINGS: Between March 19, 2019, and Nov 25, 2021, 55 participants were enrolled into cohort 1. Using the six-point face scale, 43 (83%) of participants at week 4 and 38 (73%) at week 8 reported that the injection caused "no hurt" or "hurts little bit", while only a single (2%) participant for each week rated the pain as one of the two highest pain levels. Quality of life was not diminished by the addition of one injectable antiretroviral. In-depth interviews revealed that parents and caregivers in the USA frequently had more hesitancy than adolescents about use of long-acting formulations, but parental acceptance was higher after their children received injections. INTERPRETATION: High acceptability and tolerability of long-acting cabotegravir or rilpivirine injections suggests that these are likely to be favoured treatment options for some adolescents living with HIV. FUNDING: National Institutes of Health and ViiV Healthcare.

Low maternal vitamin D is associated with increased risk of congenital and peri/postnatal transmission of Cytomegalovirus in women with HIV.

BACKGROUND: CMV infection of the fetus or neonate can lead to devastating disease, and there are no effective prevention strategies to date. Vitamin D is a potent immunomodulator, supports antiviral immune responses, and plays an important role in placental immunity. METHODS: Retrospective cohort study to evaluate the impact of low maternal vitamin D on congenital and early postnatal transmission of CMV among HIV-infected, non-breastfeeding women and their HIV exposed but negative infants from an urban HIV clinic. Vitamin D panel was performed on stored maternal plasma obtained near time of delivery. Infant CMV testing at 0-6 months included urine and oral cultures, and/or serum polymerase chain reaction testing. RESULTS: Cohort included 340 mother-infant pairs (births 1991-2014). Among 38 infants (11%) with a CMV+ test between 0-6 months, 4.7% (14/300) had congenital CMV transmission (CMV+ test 0-3 weeks), and 7.6% (24/315) had peri/postnatal CMV (CMV+ test >3 weeks-6 months). Women with lower calcitriol (1,25-dihydroxyvitamin D), the active form of vitamin D, were more likely to have an infant with congenital (OR 12.2 [95% CI 1.61-92.2] P = 0.02) and peri/postnatal (OR 9.84 [95% CI 2.63-36.8] P = 0.0007) infections in multivariate analyses, independent of maternal HIV viral load and CD4 count. CONCLUSION: This study demonstrates an association between inadequate maternal calcitriol during pregnancy and increased congenital and early postnatal acquisition of CMV among non-breastfeeding women with HIV and their HIV negative infants.

Low Bioactive Vitamin D Is Associated with Pregnancy-Induced Hypertension in a Cohort of Pregnant HIV-Infected Women Sampled Over a 23-Year Period.

OBJECTIVE: To examine the association of vitamin D insufficiency and risk of pregnancy-induced hypertension (PIH) among human immunodeficiency virus (HIV)-infected pregnant women. STUDY DESIGN: This is a retrospective cohort study evaluating the impact of low maternal vitamin D levels on PIH and perinatal outcomes among HIV-infected pregnant women receiving care at an urban HIV center from 1991 to 2014. RESULTS: A total of 366 pregnant women were included, of which 11% developed PIH. Lower levels of 25-hydroxyvitamin D (25(OH)D) and bioactive 1,25-dihydroxyvitamin D (1,25(OH)2D) were associated with increased HIV disease activity. 25(OH)D levels were not significantly associated with the incidence of PIH. Higher 1,25(OH)2D levels were associated with reduced incidence of PIH in univariate (odds ratio, OR: 0.87 [95% confidence interval, CI: 0.79-0.95], p = 0.004) and multivariate (OR: 0.88 [95% CI: 0.80-0.97], p = 0.010) analyses. No association was found between 25(OH)D levels and other obstetric outcomes. Lower 1,25(OH)2D levels were associated with group B Streptococcus colonization (OR: 0.92 [95% CI: 0.86-0.99]) and low birth weight (LBW) (OR: 0.90 [95% CI: 0.83-0.98]) on multivariate analysis. Mean 1,25(OH)2D levels were significantly lower in women with preterm delivery and LBW infants. CONCLUSION: Lower bioactive vitamin D levels are related to PIH in HIV-infected women. This association may be related to the coexistence of abnormal placental vitamin D metabolism and abnormal placental implantation.

Chlorhexidine-impregnated dressing for prevention of catheter-related bloodstream infection: a meta-analysis*.

OBJECTIVE: To assess the efficacy of a chlorhexidine-impregnated dressing for prevention of central venous catheter-related colonization and catheter-related bloodstream infection using meta-analysis. DATA SOURCES: Multiple computerized database searches supplemented by manual searches including relevant conference proceedings. STUDY SELECTION: Randomized controlled trials evaluating the efficacy of a chlorhexidine-impregnated dressing compared with conventional dressings for prevention of catheter colonization and catheter-related bloodstream infection. DATA EXTRACTION: Data were extracted on patient and catheter characteristics and outcomes. DATA SYNTHESIS: Nine randomized controlled trials met the inclusion criteria. Use of a chlorhexidine-impregnated dressing resulted in a reduced prevalence of catheter-related bloodstream infection (random effects relative risk, 0.60; 95% CI, 0.41-0.88, p = 0.009). The prevalence of catheter colonization was also markedly reduced in the chlorhexidine-impregnated dressing group (random effects relative risk, 0.52; 95% CI, 0.43-0.64; p < 0.001). There was significant benefit for prevention of catheter colonization and catheter-related bloodstream infection, including arterial catheters used for hemodynamic monitoring. Other than in low birth weight infants, adverse effects were rare and minor. CONCLUSIONS: Our analysis shows that a chlorhexidine-impregnated dressing is beneficial in preventing catheter colonization and, more importantly, catheter-related bloodstream infection and warrants routine use in patients at high risk of catheter-related bloodstream infection and central venous catheter or arterial catheter colonization.

Black spots in the returning traveler.

African tick bite fever (ATBF) is a rickettsial infection that should be considered as the cause of fever in travelers returning from endemic regions of sub-Saharan Africa or the Caribbean. Patients typically present with a flu-like syndrome and may demonstrate one or more cutaneous inoculation eschars as a diagnostic key. We present a case of ATBF in a pregnant woman following her trip to Swaziland. Her symptoms rapidly improved with institution of effective antimicrobial treatment with azithromycin and rifampin; she made a full recovery.

Cross-sectional study of vitamin D levels, immunologic and virologic outcomes in HIV-infected adults.

CONTEXT: Vitamin D is increasingly recognized as an important immunomodulator. Lower levels of 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH]2D) are observed in persons living with HIV. OBJECTIVE: The purpose of this study was to evaluate the relationship of 25(OH)D, and 1,25(OH)2D to HIV viral load, and CD4+ T cells in HIV-infected adults. DESIGN: This was a cross-sectional study completed between January 2010 and April 2011. SETTING: This study was conducted with volunteers who received HIV care in Wisconsin at either a University-based HIV clinic or an urban community HIV clinic. PATIENTS: One hundred twelve adults with HIV infection participated in this study. MAIN OUTCOME MEASURES: The primary outcome for this study was the relationship between 1,25(OH)2D and HIV viral load. Secondary outcomes included relationships between 25(OH)D and HIV viral load, 25(OH)D and 1,25(OH)2D to CD4+ T cells, and predictors of vitamin D deficiency. RESULTS: The 112 volunteers included 24 women and 3 transgender individuals; 68% were from the university clinic, and 32% were from the urban clinic. Mean age was 44.2 years. The mean 25(OH)D level was 22.5 ng/mL; mean 1,25(OH)2D level was 23.5 pg/mL. Twenty-two percent had 25(OH)D ≤10 ng/mL; 53% had values <20 ng/mL, and 73% were ≤30 ng/mL. There was no association between vitamin D and CD4. A nonlinear relationship between viral load and 1,25(OH)2D was found. For 1,25(OH)2D below 32 pg/mL, for each 10 pg/mL decrease in 1,25(OH)2D, (log10) viral load increased by 0.84 (95% CI: 0.16-1.51, P = .015). For 1,25(OH)2D above 32 pg/mL, for each 10 pg/mL increase in 1,25(OH)2D, (log10) viral load increased by 0.36 (95% CI: 0.15-0.57, P = .0009). CONCLUSION: Vitamin D deficiency was common in this HIV population, as seen in other HIV cohorts. A novel, U-shaped relationship between 1,25(OH)2D and viral load, with the lowest and highest 1,25(OH)2D levels seen with high viral loads, was found and deserves further study.

An outbreak of the 2009 influenza a (H1N1) virus in a children's hospital.

CONTEXT: Preventing nosocomial transmission of influenza is essential to reduce the morbidity and mortality associated with this infection. In October 2009, an outbreak of the 2009 influenza A (H1N1) virus occurred in a hematology ward of a children's hospital over a 21-day period and involved two patients and four healthcare workers. OBJECTIVE: To investigate nosocomial transmission of the 2009 influenza A (H1N1) virus in patients and healthcare workers. DESIGN, SETTING, AND PARTICIPANTS: An outbreak investigation was initiated in response to suspected nosocomial transmission of the 2009 influenza A (H1N1) virus during the peak of the 2009 pandemic. Cases were confirmed using a polymerase chain reaction (PCR) test specific for the 2009 H1N1 influenza A virus. Viruses isolated from nasopharyngeal swabs were genetically characterized using Sanger sequencing of uncloned "bulk" PCR products. MAIN OUTCOME MEASURES: Virus sequencing to investigate nosocomial transmission. RESULTS: Two immunocompromised patients and four healthcare workers were found to be part of a nosocomial outbreak of the 2009 influenza A (H1N1) virus. One immunocompromised patient had a second episode of clinical influenza infection after isolation precautions had been discontinued, resulting in additional exposures. Strain-specific PCR showed that all cases were caused by infection of the 2009 H1N1 virus. Sequencing of viral genes encoding hemagglutinin and polymerase basic subunit 2 (PB2) revealed that all viruses isolated were genetically identical at these loci, including the two episodes occurring in the same immunocompromised patient. CONCLUSIONS: Prompt institution of isolation precautions is essential in preventing nosocomial outbreaks of the 2009 novel influenza A (H1N1) virus. Our data suggest that isolation precautions may need to be continued for a prolonged period of time in immunocompromised patients with influenza infection.

Vitamin D and the anti-viral state.

Vitamin D has long been recognized as essential to the skeletal system. Newer evidence suggests that it also plays a major role regulating the immune system, perhaps including immune responses to viral infection. Interventional and observational epidemiological studies provide evidence that vitamin D deficiency may confer increased risk of influenza and respiratory tract infection. Vitamin D deficiency is also prevalent among patients with HIV infection. Cell culture experiments support the thesis that vitamin D has direct anti-viral effects particularly against enveloped viruses. Though vitamin D's anti-viral mechanism has not been fully established, it may be linked to vitamin D's ability to up-regulate the anti-microbial peptides LL-37 and human beta defensin 2. Additional studies are necessary to fully elucidate the efficacy and mechanism of vitamin D as an anti-viral agent.