Genomics Links Inflammation With Neurocognitive Impairment in Children Living With Human Immunodeficiency Virus Type-1.

BACKGROUND: We identified host single-nucleotide variants (SNVs) associated with neurocognitive impairment (NCI) in perinatally HIV-infected (PHIV) children. METHODS: Whole-exome sequencing (WES) was performed on 217 PHIV with cognitive score for age (CSA) < 70 and 247 CSA ≥ 70 (discovery cohort [DC]). SNVs identified in DC were evaluated in 2 validation cohorts (VC). Logistic regression was used to estimate adjusted odds ratios (ORs) for NCI. A human microglia NLRP3 inflammasome assay characterized the role of identified genes. RESULTS: Twenty-nine SNVs in 24 genes reaching P ≤ .002 and OR ≥ 1.5 comparing CSA < 70 to CSA ≥ 70 were identified in the DC, of which 3 SNVs were identified in VCs for further study. Combining the 3 cohorts, SNV in CCRL2 (rs3204849) was associated with decreased odds of NCI (P < .0001); RETREG1/FAM134B (rs61733811) and YWHAH (rs73884247) were associated with increased risk of NCI (P < .0001 and P < .001, respectively). Knockdown of CCRL2 led to decreased microglial release of IL-1ß following exposure to ssRNA40 while knockdown of RETREG1 and YWHAH resulted in increased IL-1ß release. CONCLUSIONS: Using WES and 2 VCs, and gene silencing of microglia we identified 3 genetic variants associated with NCI and inflammation in HIV-infected children.

Suubi+Adherence study protocol: A family economic empowerment intervention addressing HIV treatment adherence for perinatally infected adolescents.

BACKGROUND: Globally, 1.8 million children<15 years are living with HIV. Sub-Saharan Africa (SSA), as a region, is heavily burdened by HIV, with 90% of new infections among children happening there. Within SSA, Uganda has an HIV prevalence of 7.2% among 15-49-year-olds, with high prevalence in Masaka region (12%). Uganda also reports unprecedented numbers of perinatally HIV-infected children, with close to 150,000 children (ages 0-14) living with HIV (CLHA). However adherence to antiretroviral therapy (ART) among children and youth is poor, and has been attributed to economic insecurity, including lack of finances for transportation to clinic appointments, inadequate meals to support medication consumption, and resource prioritization towards school expenses. Yet, few programs aimed at addressing ART adherence have applied combination interventions to address economic stability and ART Adherence within the traditional framework of health education and HIV care. This paper describes a study protocol for a 5-year, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) funded, cluster randomized-controlled trial to evaluate a combination intervention, titled Suubi + Adherence, aimed at improving ART adherence among HIV perinatally infected adolescents (ages 10-16 at study enrollment) in Uganda. METHODS: Suubi + Adherence was evaluated via a two-arm cluster randomized-controlled trial design in 39 health clinics, with a total enrollment of 702 HIV + adolescents (ages 10-16 at enrollment). The study addresses two primary outcomes: 1) adherence to HIV treatment regimen and 2) HIV knowledge and attitudes. Secondary outcomes include family functioning, sexual risk-taking behavior, and financial savings behavior. For potential scale-up, cost effectiveness analysis was employed to compare the relative costs and outcomes associated with each study arm: family economic strengthening comprising matched savings accounts, financial management training and small business development, all intended for family economic security versus bolstered usual care (SOC) comprising enhanced adherence sessions to ensure more standardized and sufficient adherence counseling. DISCUSSION: This study aims to advance knowledge and inform the development of the next generation of programs aimed at increasing adherence to HIV treatment for HIV + adolescents in low-resource regions such as SSA. To our knowledge, the proposed study is the first to integrate and test family economic empowerment and stability-focused interventions for HIV + adolescents in Uganda (and much of SSA)-so families would have the necessary finances to manage HIV/AIDS as a chronic illness. The study would provide crucial evidence about the effects of an economic empowerment program on short and long-term impact, which is essential if such interventions are to be taken to scale. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (registration number: NCT01790373) on 13 February 2013.

Case series of infertility amongst young women with perinatally acquired HIV: data from a London cohort.

INTRODUCTION: Increased rates of infertility have been reported in women who acquired HIV horizontally compared to population age-matched normative data. However, few data exist for adults with perinatally acquired HIV (PaHIV), who have been exposed to antiretroviral drugs and/or HIV-associated ill health through childhood and puberty. We describe a case series of infertility amongst women with PaHIV attending a London clinic between 2006 and 2017. METHODS: A retrospective case-note review was conducted amongst all female PaHIV patients aged >16 years attending a London clinic. All data was captured into an electronic database using paper and electronic clinical records taken from every routine clinic visit (average three times/year between 2006 and 2017). Data captured included HIV viral load, CD4 cell count, antiretroviral therapy regimen, sexual and reproductive health and STI screening. Age-matched analysis of infertility rates compared to the general population were not performed. RESULTS: In total, 119 young women were included, with a median age of 20 years (interquartile range [IQR] 18-24, range 16-33 years) at latest follow-up. Three women with PaHIV were diagnosed with infertility (n=3): two with primary ovarian insufficiency (n=2) and one with hypogonadotropic hypogonadism (n=1). A further 5/116 (4.3%) were under investigation for menstrual irregularities. Of the remaining 111 young women, 17 (15%) had successfully conceived. All patients were currently prescribed ART, with 93 (78%) having an HIV VL <50 copies/mL at their last visit. Median ART exposure was 13 (IQR 9-17) years. Among five women with reported irregular menstrual cycles there was no correlation with current CD4 cell count, HIV VL or length of ART exposure, although there was an increased prevalence of body mass index >25 kg/m2 (63% vs 30%). CONCLUSION: Overall the reproductive health status for young women with PaHIV was comparable to the general population.

Cytomegalovirus Urinary Shedding in HIV-infected Pregnant Women and Congenital Cytomegalovirus Infection.

BACKGROUND: Cytomegalovirus (CMV) urinary shedding in pregnant women infected with human immunodeficiency virus (HIV) was evaluated to determine whether it poses an increased risk for congenital CMV infection (cCMV). METHODS: A subset of mother-infant pairs enrolled in the perinatal NICHD HPTN 040 study (distinguished by no antiretroviral use before labor) was evaluated. Maternal and infant urines were tested by qualitative real-time polymerase chain reaction (RT-PCR) for CMV DNA with quantitative RT-PCR performed on positive specimens. RESULTS: Urine specimens were available for 260 women with 85.4% from the Americas and 14.6% from South Africa. Twenty-four women (9.2%) had detectable CMV viruria by qualitative PCR. Maternal CMV viruria was not associated with mean CD4 cell counts or HIV viral load but was associated with younger maternal age (P = .02). Overall, 10 of 260 infants (3.8%) had cCMV. Women with detectable peripartum CMV viruria were more likely to have infants with cCMV than those without: 20.8% (5/24) versus 2.1% (5/236), (P = .0001). Women with CMV viruria had significantly higher rates of HIV perinatal transmission (29.2% vs. 8.1%, P = .002). They were 5 times (adjusted odds ratio [aOR] = 5.6, 95% confidence interval [CI] 1.9-16.8) and nearly 30 times (aOR, 29.7; 95% CI, 5.4-164.2) more likely to transmit HIV and CMV to their infants, respectively. Maternal gonorrhea (aOR, 19.5; 95% CI, 2.5-151.3) and higher maternal HIV log10 viral load (OR, 2.8; 95% CI, 1.3-6.3) were also significant risk factors for cCMV. CONCLUSION: In this cohort of HIV-infected pregnant women not on antiretrovirals, urinary CMV shedding was a significant risk factor for CMV and HIV transmission to infants. CLINICAL TRIALS REGISTRATION NUMBER: NCT00099359.

Assessing the Impact of Perinatal HIV Case Management on Outcomes Along the HIV Care Continuum for Pregnant and Postpartum Women Living With HIV, Philadelphia 2005-2013.

To evaluate the impact of a Perinatal Medical Case Management (PCM) Program for women living with HIV (WLWH). Characteristics of pregnant and postpartum WLWH were compared between those who engaged in PCM and those who did not. Using secondary data collected from routine HIV surveillance, multivariable regression models were used to evaluate the association between PCM and four outcomes adapted from the HIV care continuum. In multivariable models, compared to WLWH not in PCM, participants (n = 448, 52.8%) were almost twice as likely to achieve HIV suppression before delivery (aOR 1.90 [1.33, 2.71], p = 0.0005); were more likely to be retained in HIV care 1 year postpartum (aOR 1.59 [1.17, 2.16], p = 0.0029); and were equally likely to engage in HIV care within 90-days of delivery (aOR 1.21 [0.88, 1.65], p = 0.236) and be virally suppressed 1 year postpartum (aOR 1.26 [0.90, 1.77], p = 0.178). PCM is an important intervention for preventing perinatal HIV transmission and closings gaps in the HIV care continuum for WLWH during pregnancy and postpartum.

Actulización en profilaxis de la transmisión vertical del VIH / Prophylaxis of perinatal HIV transmission: update

Existe un innegable avance en términos de prevención de la transmisión perinatal del VIH, aunque el acceso a las estrategias de reducción continúa siendo limitado en la mayoría de los países pobres y en algunas poblaciones de los países ricos. En la actualidad se dispone de un mejor conocimiento de intervenciones ya probadas y datos sobre nuevos escenarios y acciones preventivas. Los hallazgos más recientes en cada una de ellos se resumen en éste artículo.

There is an undeniable progress in terms of prevention of perinatal transmission of HIV, although access to reduction strategies remains limited in most poor countries and in some populations of rich countries. At present here is a better understanding of proven interventions and data on new scenarios and preventive actions. The latest findings are summarized in this article.

Actulización en profilaxis de la transmisión vertical del VIH / Prophylaxis of perinatal HIV transmission: update

Existe un innegable avance en términos de prevención de la transmisión perinatal del VIH, aunque el acceso a las estrategias de reducción continúa siendo limitado en la mayoría de los países pobres y en algunas poblaciones de los países ricos. En la actualidad se dispone de un mejor conocimiento de intervenciones ya probadas y datos sobre nuevos escenarios y acciones preventivas. Los hallazgos más recientes en cada una de ellos se resumen en éste artículo.(AU)

There is an undeniable progress in terms of prevention of perinatal transmission of HIV, although access to reduction strategies remains limited in most poor countries and in some populations of rich countries. At present here is a better understanding of proven interventions and data on new scenarios and preventive actions. The latest findings are summarized in this article.(AU)