Treatment Experience and Repeat Pregnancy Impact the Effectiveness of Non-Nucleoside Reverse Transcription Inhibitor-Highly Active Antiretroviral Therapy for the Prevention of Mother to Child Transmission of Human Immunodeficiency Virus.

Non-nucleoside reverse transcription inhibitor (NNRTI)-containing antiretroviral therapy (ART) for the prevention of mother to child transmission (PMTCT) of human immunodeficiency virus (HIV) has led to dramatic reductions in perinatal HIV infection in resource-constrained settings. Nonetheless, PMTCT programs are complicated by repeat pregnancies, in which long-term or repeat exposures to PMTCT regimens over time may lead to the acquisition of HIV drug resistance mutations, and consequent treatment failure. In this study, we retrospectively assessed the effectiveness of the NNRTI-based PMTCT protocol from 2008 to 2010 in The Bahamas National HIV/AIDS Program. We show that women who had been in repeat pregnancies and those who were already prescribed ART at conception were at increased risk of virologic failure, relative to treatment-inexperienced women and primigravida, respectively (AOR 3.1, 95% CI: 1.3-7.1, p = .008 and AOR 5.0, 95% CI: 1.8-14.1, p = .002). In addition, women undergoing treatment at conception were more likely to possess HIVDR mutations relative to treatment-naive women (AOR 447.1, 95% CI: 17.9-11,173.5, p = .001). Therefore, individual treatment history is a key metric determining the effectiveness of current and future PMTCT interventions. The implications of this to PMTCT programmatic success in light of the most recent WHO guidelines are discussed.

HIV testing barriers and intervention strategies among men, transgender women, female sex workers and incarcerated persons in the Caribbean: a systematic review.

BACKGROUND: This systematic review summarises evidence on the HIV testing barriers and intervention strategies among Caribbean populations and provides pertinent implications for future research endeavours designed to increase rates of HIV testing in the region. METHODS: We used a systematic approach to survey all literature published between January 2008 and November 2018 using four electronic databases (MEDLINE/PubMed, Embase, Web of Science and Global Health). Only peer-reviewed articles published in English that examined HIV testing uptake and interventions in the Caribbean with men, men who have sex with men, female sex workers, transgender women and incarcerated individuals were included. RESULTS: Twenty-one studies met the inclusion criteria. Lack of confidentiality, access to testing sites, stigma, discrimination, poverty and low HIV risk perception were identified as key barriers to HIV testing. These barriers often contributed to late HIV testing and were associated with delayed treatment initiation and decreased survival rate. Intervention strategies to address these barriers included offering rapid HIV testing at clinics and HIV testing outreach by trained providers and peers. CONCLUSION: HIV testing rates remain unacceptably low across the Caribbean for several reasons, including stigma and discrimination. Future HIV testing interventions should target places where at-risk populations congregate, train laypersons to conduct rapid tests and consider using oral fluid HIV self-testing, which allows individuals to test at home.

Performance of and preference for oral rapid HIV testing in The Bahamas.

Initiatives to increase access to quality rapid HIV diagnostics have had relative success in the Caribbean in recent years, including use of oral rapid HIV testing. However, to date, there has not been any investigation into the performance or acceptability of oral fluids HIV testing in the region. In this cross-sectional study in The Bahamas, 252 persons of unknown serostatus were tested side-by-side with two oral rapid test brands, and the results were compared with the national fingerprick algorithm. In addition, an exit survey was administered to 234 study participants to assess user test preference. The most frequent survey response was to have no test preference (47.8%), but of those who expressed a test preference, most preferred oral (34.4%) versus fingerprick (17.8%) method. Both OraQuick and AWARE were 100% concordant with the gold standard. Therefore, our results show that oral fluids rapid testing is preferred over fingerprick testing by a subset of the potential target population and performs well in a population of undiagnosed persons attending screening clinic in The Bahamas.

The HIV continuum of care in the Bahamas in 2014 / El proceso continuo de atención de la infección por el VIH en las Bahamas en el 2014

ABSTRACT Objective The HIV cascade of care describes the spectrum of engagement in HIV care from diagnosis to viral suppression (VS). The study objective was to develop a baseline HIV cascade of care for new HIV diagnoses in the Bahamas in 2014. Methods Individuals who were newly diagnosed with HIV in 2014 and known to be alive within a year of that diagnosis were included in the cascade of care (n = 250). Individuals with one CD4 or HIV viral load (VL) measure in 2014 were considered linked to care. Those with at least two CD4 counts in the year were considered retained in care. Eligibility for antiretroviral therapy (ART) was based on having a CD4 count < 350 cells/mm3. ART adherence was defined as filled prescriptions > 11 months/year. VL < 1 000 copies/ml was considered suppressed. Comparisons were made in the cascades by gender and age. Results Of the 250 persons in the study, 79 of them (32%) were retained in care. Antiretrovirals (ARVs) were prescribed to 116 of the 250 (46%); of those 116, 48 of them (41%) achieved VS. A higher proportion of women achieved VS than did men, but this difference did not reach statistical significance. Similarly, there were differences in VS based on age, but the differences were not statistically significant. Conclusions In the Bahamas, increased efforts are needed to help people living with HIV to link to and be retained in care. VS may remain suboptimal unless ART is scaled up and adherence interventions are included in measures to improve the treatment cascade.

RESUMEN Objetivo El proceso continuo de la atención de la infección por el VIH describe el espectro de intervenciones en la atención de la infección, desde el diagnóstico hasta la supresión viral. El objetivo del estudio fue elaborar un proceso continuo de la atención como punto de referencia y comparación para nuevos diagnósticos de infección por el VIH en las Bahamas en el 2014. Métodos En el proceso continuo de la atención se incluyó a personas con diagnóstico de infección por el VIH en el 2014 y que continuaban vivas a un año del diagnóstico (n = 250). Se consideró vinculadas a la atención a aquellas personas con un recuento de linfocitos CD4 o una medición de la carga viral de VIH en el 2014. Aquellas con al menos dos recuentos de CD4 en el año se consideraron retenidas en la atención. La aptitud para el tratamiento antirretroviral se basó en tener un recuento de CD4 < 350 células/mm3. Se definió adherencia al tratamiento antirretroviral como la entrega de la prescripción >11 meses/año. Se consideró supresión viral a una carga viral de < 1 000 copias/ml. Se hicieron comparaciones en las cascadas por sexo y edad. Resultados De las 250 personas que participaron en el estudio, 79 (32%) se retuvieron en la atención. Se prescribieron antirretrovirales a 116 de las 250 personas (46%); de estas 116 personas, 48 (41%) lograron la supresión viral. Las mujeres lograron la supresión viral en una proporción mayor que los hombres, pero esta diferencia no fue estadísticamente significativa. Igualmente, se observaron diferencias en la supresión viral según la edad, pero estas tampoco fueron estadísticamente significativas. Conclusiones En las Bahamas, es necesario incrementar los esfuerzos para ayudar a las personas con infección por el VIH a vincularse y mantenerse en la atención. La supresión viral puede permanecer en niveles subóptimos a menos que se amplíe el tratamiento antirretroviral y se incluyan intervenciones de adherencia terapéutica en las medidas para mejorar el proceso continuo de la atención.

The HIV continuum of care in the Bahamas in 2014 / El proceso continuo de atención de la infección por el VIH en las Bahamas en el 2014

Objective. The HIV cascade of care describes the spectrum of engagement in HIV care from diagnosis to viral suppression (VS). The study objective was to develop a baseline HIV cascade of care for new HIV diagnoses in the Bahamas in 2014. Methods. Individuals who were newly diagnosed with HIV in 2014 and known to be alive within a year of that diagnosis were included in the cascade of care (n = 250). Individuals with one CD4 or HIV viral load (VL) measure in 2014 were considered linked to care. Those with at least two CD4 counts in the year were considered retained in care. Eligibility for antiretroviral therapy (ART) was based on having a CD4 count < 350 cells/mm3. ART adherence was defined as filled prescriptions > 11 months/year. VL < 1 000 copies/ml was considered suppressed. Comparisons were made in the cascades by gender and age. Results. Of the 250 persons in the study, 79 of them (32%) were retained in care. Antiretrovirals (ARVs) were prescribed to 116 of the 250 (46%); of those 116, 48 of them (41%) achieved VS. A higher proportion of women achieved VS than did men, but this difference did not reach statistical significance. Similarly, there were differences in VS based on age, but the differences were not statistically significant. Conclusions. In the Bahamas, increased efforts are needed to help people living with HIV to link to and be retained in care. VS may remain suboptimal unless ART is scaled up and adherence interventions are included in measures to improve the treatment cascade.

Objetivo. El proceso continuo de la atención de la infección por el VIH describe el espectro de intervenciones en la atención de la infección, desde el diagnóstico hasta la supresión viral. El objetivo del estudio fue elaborar un proceso continuo de la atención como punto de referencia y comparación para nuevos diagnósticos de infección por el VIH en las Bahamas en el 2014. Métodos. En el proceso continuo de la atención se incluyó a personas con diagnóstico de infección por el VIH en el 2014 y que continuaban vivas a un año del diagnóstico (n = 250). Se consideró vinculadas a la atención a aquellas personas con un recuento de linfocitos CD4 o una medición de la carga viral de VIH en el 2014. Aquellas con al menos dos recuentos de CD4 en el año se consideraron retenidas en la atención. La aptitud para el tratamiento antirretroviral se basó en tener un recuento de CD4 < 350 células/mm3. Se definió adherencia al tratamiento antirretroviral como la entrega de la prescripción >11 meses/año. Se consideró supresión viral a una carga viral de < 1 000 copias/ml. Se hicieron comparaciones en las cascadas por sexo y edad. Resultados. De las 250 personas que participaron en el estudio, 79 (32%) se retuvieron en la atención. Se prescribieron antirretrovirales a 116 de las 250 personas (46%); de estas 116 personas, 48 (41%) lograron la supresión viral. Las mujeres lograron la supresión viral en una proporción mayor que los hombres, pero esta diferencia no fue estadísticamente significativa. Igualmente, se observaron diferencias en la supresión viral según la edad, pero estas tampoco fueron estadísticamente significativas. Conclusiones. En las Bahamas, es necesario incrementar los esfuerzos para ayudar a las personas con infección por el VIH a vincularse y mantenerse en la atención. La supresión viral puede permanecer en niveles subóptimos a menos que se amplíe el tratamiento antirretroviral y se incluyan intervenciones de adherencia terapéutica en las medidas para mejorar el proceso continuo de la atención.

The HIV continuum of care in the Bahamas in 2014.

OBJECTIVE: The HIV cascade of care describes the spectrum of engagement in HIV care from diagnosis to viral suppression (VS). The study objective was to develop a baseline HIV cascade of care for new HIV diagnoses in the Bahamas in 2014. METHODS: Individuals who were newly diagnosed with HIV in 2014 and known to be alive within a year of that diagnosis were included in the cascade of care (n = 250). Individuals with one CD4 or HIV viral load (VL) measure in 2014 were considered linked to care. Those with at least two CD4 counts in the year were considered retained in care. Eligibility for antiretroviral therapy (ART) was based on having a CD4 count < 350 cells/mm3. ART adherence was defined as filled prescriptions > 11 months/year. VL < 1 000 copies/ml was considered suppressed. Comparisons were made in the cascades by gender and age. RESULTS: Of the 250 persons in the study, 79 of them (32%) were retained in care. Antiretrovirals (ARVs) were prescribed to 116 of the 250 (46%); of those 116, 48 of them (41%) achieved VS. A higher proportion of women achieved VS than did men, but this difference did not reach statistical significance. Similarly, there were differences in VS based on age, but the differences were not statistically significant. CONCLUSIONS: In the Bahamas, increased efforts are needed to help people living with HIV to link to and be retained in care. VS may remain suboptimal unless ART is scaled up and adherence interventions are included in measures to improve the treatment cascade.

F3/contactin and TAG1 play antagonistic roles in the regulation of sonic hedgehog-induced cerebellar granule neuron progenitor proliferation.

Modulation of the sonic hedgehog (SHH) pathway is a crucial factor in cerebellar morphogenesis. Stimulation of granule neuron progenitor (GNP) proliferation is a central function of SHH signalling, but how this is controlled locally is not understood. We show that two sequentially expressed members of the contactin (CNTN) family of adhesion molecules, TAG1 and F3, act antagonistically to control SHH-induced proliferation: F3 suppresses SHH-induced GNP proliferation and induces differentiation, whereas TAG1 antagonises F3. Production of GNPs in TAG1-null mice is delayed and reduced. F3 and TAG1 colocalise on GNPs with the related L1-like adhesion molecule NrCAM, and F3 fails to suppress the SHH-induced proliferation of NrCAM-deficient GNPs. We show that F3 and SHH both primarily affect a group of intermediate GNPs (IPs), which, though actively dividing, also express molecules associated with differentiation, including ß-tubulin III (TuJ1) and TAG1. In vivo, intermediate progenitors form a discrete layer in the middle of the external germinal layer (mEGL), while F3 becomes expressed on the axons of postmitotic granule neurons as they leave the inner EGL (iEGL). We propose, therefore, that F3 acts as a localised signal in the iEGL that induces SHH-stimulated cells in the overlying mEGL to exit cell cycle and differentiate. By contrast, expression of TAG1 on GNPs antagonises this signal in the mEGL, preventing premature differentiation and sustaining GNP expansion in a paracrine fashion. Together, these findings indicate that CNTN and L1-like proteins play a significant role in modulating SHH-induced neuronal precursor proliferation.