Perspectives of healthcare providers around providing family planning services to women living with HIV attending six HIV treatment clinics in Lusaka, Zambia.

While international guidelines recommend integration of family planning (FP) and HIV services, limited research has been done to explore how healthcare providers perceive the feasibility and utility of integrated services. To address this gap, we administered a standardized questionnaire to 85 providers from 6 HIV clinics in Lusaka, Zambia, before (April-May 2018) and after (May-June 2019) implementing an enhanced model of FP/HIV service integration. We tested for differences in FP knowledge, attitudes and practices between the two time periods with tests appropriate for paired observations.

Impact of a monitoring and evaluation training in 3 PEPFAR-supported countries.

Background: The second phase of the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) transitioned from scaling up HIV prevention and treatment to promoting sustainability and capacity building for programs monitoring performance and evaluating key program indicators.

Evaluating analytic models for individually randomized group treatment trials with complex clustering in nested and crossed designs.

Many individually randomized group treatment (IRGT) trials randomly assign individuals to study arms but deliver treatments via shared agents, such as therapists, surgeons, or trainers. Post-randomization interactions induce correlations in outcome measures between participants sharing the same agent. Agents can be nested in or crossed with trial arm, and participants may interact with a single agent or with multiple agents.

Sinonasal DLBCL: molecular profiling identifies subtypes with distinctive prognosis and targetable genetic features.

Primary sinonasal diffuse large B-cell lymphoma (PSDLBCL) is a rare lymphoma with a variable prognosis and a unique relapse/dissemination pattern involving the central nervous system and skin. The underlying molecular mechanisms leading to this heterogeneity and progression pattern remain uncharted, hampering patient-tailored treatment. To investigate associated mechanisms, we analyzed clinical data and used immunohistochemistry, gene-expression profiling, cytogenetics, and next-generation sequencing in a cohort of 117 patients with PSDLBCL.

More Frequent HIV Viral Load Testing With Point-Of-Care Tests Detects Elevated Viral Load Earlier in Postpartum HIV-Positive Women in a Randomized Controlled Trial in Two Clinics in Johannesburg, South Africa.

Background: Elevated maternal HIV viral load (VL) increases vertical transmission risk for breastfeeding children. This randomized controlled trial in Johannesburg primarily evaluated whether 3-monthly point-of-care testing, with laboratory-based standard-of-care testing (arm 2), compared with 6-monthly laboratory-based VL testing (arm 1) in postpartum women living with HIV receiving first-line tenofovir-emtricitabine-efavirenz antiretroviral treatment improved VL suppression, factors associated with nonsuppression, and drug resistance in those with virologic failure.

Methods: Mother-child pairs were enrolled July 2018-April 2019 at the child's 6/10/14-week clinic visit.

Impact of HIV treat-all and complementary policies on ART linkage in 13 PEPFAR-supported African countries.

Background: In 2015, the World Health Organization recommended that all people living with HIV begin antiretroviral treatment (ART) regardless of immune status, a policy known as 'Treat-All to end AIDS', commonly referred to as Treat-All. Almost all low- and middle-income countries adopted this policy by 2019. This study describes how linkage to treatment of newly diagnosed persons changed between 2015 and 2018 and how complementary policies may have similarly increased linkage for 13 African countries.

Assessing sex differences in viral load suppression and reported deaths using routinely collected program data from PEPFAR-supported countries in sub-Saharan Africa.

Background: In sub-Saharan Africa, more women than men access HIV testing and treatment and may have better viral load suppression (VLS). We utilized routinely reported aggregated HIV program data from 21 sub-Saharan African countries to examine sex differences in VLS and death rates within antiretroviral therapy (ART) programs supported by the United States President's Emergency Plan for AIDS Relief (PEPFAR).

Methods: We included VLS and reported death data for persons aged 15 + years on ART from October-December 2020 disaggregated by sex and age for each subnational unit (SNU).

Retrospective longitudinal analysis of low-level viremia among HIV-1 infected adults on antiretroviral therapy in Kenya.

Background: HIV low-level viremia (LLV) (51-999 copies/mL) can progress to treatment failure and increase potential for drug resistance. We analyzed retrospective longitudinal data from people living with HIV (PLHIV) on antiretroviral therapy (ART) in Kenya to understand LLV prevalence and virologic outcomes.

Methods: We calculated rates of virologic suppression (≤50 copies/mL), LLV (51-999 copies/mL), virologic non-suppression (≥1000 copies/mL), and virologic failure (≥2 consecutive virologic non-suppression results) among PLHIV aged 15 years and older who received at least 24 weeks of ART during 2015-2021.

The oncogenic human B-cell lymphoma MYD88 L265P mutation genocopies activation by phosphorylation at the Toll/interleukin-1 receptor (TIR) domain.

MYD88 is the key signaling adaptor-protein for Toll-like and interleukin-1 receptors. A somatic L265P mutation within the Toll/interleukin-1 receptor (TIR) domain of MYD88 is found in 90% of Waldenström macroglobulinemia cases and in a significant subset of diffuse large B-cell lymphomas. MYD88-L265P strongly promotes NF-κB pathway activation, JAK-STAT signaling and lymphoma cell survival.

Expanded ILC2s in human infant intestines promote tissue growth.

Early life is characterized by extraordinary challenges, including rapid tissue growth and immune adaptation to foreign antigens after birth. During this developmental stage, infants have an increased risk of immune-mediated diseases. Here, we demonstrate that tissue-resident, interleukin (IL)-13- and IL-4-producing group 2 innate lymphoid cells (ILC2s) are enriched in human infant intestines compared to adult intestines.

MALT1-dependent cleavage of CYLD promotes NF-κB signaling and growth of aggressive B-cell receptor-dependent lymphomas.

The paracaspase mucosa-associated lymphoid tissue 1 (MALT1) is a protease and scaffold protein essential in propagating B-cell receptor (BCR) signaling to NF-κB. The deubiquitinating enzyme cylindromatosis (CYLD) is a recently discovered MALT1 target that can negatively regulate NF-κB activation. Here, we show that low expression of CYLD is associated with inferior prognosis of diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) patients, and that chronic BCR signaling propagates MALT1-mediated cleavage and, consequently, inactivation and rapid proteasomal degradation of CYLD.

HIV Viral Load Scale-up Among Children and Adolescents: Trends in Viral Load Suppression, Sample Type and Processing in 7 PEPFAR Countries, 2015-2018.

HIV-positive children and adolescents face gaps in viral load (VL) testing. To understand trends in pediatric/adolescent VL testing, 7 countries collected data from Laboratory Information Management Systems. Results showed increasing proportion of VL tests done through dried blood spot (DBS) and decreased sample rejection rates for DBS compared with plasma, supporting use of DBS VL when skilled phlebotomy is unavailable.

Evaluation of Community-Based, Mobile HIV-Care, Peer-Delivered Linkage Case Management in Manzini Region, Eswatini.

The success of antiretroviral therapy (ART) requires continuous engagement in care and optimal levels of adherence to achieve sustained HIV viral suppression. We evaluated HIV-care cascade costs and outcomes of a community-based, mobile HIV-care, peer-delivered linkage case-management program (CommLink) implemented in Manzini region, Eswatini. Abstraction teams visited referral facilities during July 2019-April 2020 to locate, match, and abstract the clinical data of CommLink clients diagnosed between March 2016 and March 2018.

CXCR5PD-1 CD4 T cells colonize infant intestines early in life and promote B cell maturation.

Gastrointestinal infections are a major cause for serious clinical complications in infants. The induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5PD-1 CD4 T cells (T cells). We investigated the ontogeny of CXCR5PD-1 CD4 T cells in human intestines.

An Evaluation of an Enhanced Model of Integrating Family Planning Into HIV Treatment Services in Zambia, April 2018-June 2019.

Background: We designed and implemented an enhanced model of integrating family planning (FP) into existing HIV treatment services at 6 health facilities in Lusaka, Zambia.

Methods: The enhanced model included improving FP documentation within HIV monitoring systems, training HIV providers in FP services, offering contraceptives within the HIV clinic, and facilitated referral to community-based distributors. Independent samples of women living with HIV (WLHIV) aged ≥16 years were interviewed before and after intervention and their clinical data abstracted from medical charts.

Inhibition of casein kinase 2 sensitizes mantle cell lymphoma to venetoclax through MCL-1 downregulation.

BCL-2 family proteins are frequently aberrantly expressed in mantle cell lymphoma (MCL). Recently, the BCL-2-specific inhibitor venetoclax has been approved by the US Food and Drug Administration for chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). In MCL, venetoclax has shown promising efficacy in early clinical trials; however, a significant subset of patients is resistant.

A loss-of-adhesion CRISPR-Cas9 screening platform to identify cell adhesion-regulatory proteins and signaling pathways.

The clinical introduction of the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, which targets B-cell antigen-receptor (BCR)-controlled integrin-mediated retention of malignant B cells in their growth-supportive lymphoid organ microenvironment, provided a major breakthrough in lymphoma and leukemia treatment. Unfortunately, a significant subset of patients is intrinsically resistant or acquires resistance against ibrutinib. Here, to discover novel therapeutic targets, we present an unbiased loss-of-adhesion CRISPR-Cas9 knockout screening method to identify proteins involved in BCR-controlled integrin-mediated adhesion.

Antiretroviral therapy initiation and retention among clients who received peer-delivered linkage case management and standard linkage services, Eswatini, 2016-2020: retrospective comparative cohort study.

Background: Persons living with HIV infection (PLHIV) who are diagnosed in community settings in sub-Saharan Africa are particularly vulnerable to barriers to care that prevent or delay many from obtaining antiretroviral therapy (ART).

Methods: We conducted a retrospective cohort study to assess if a package of peer-delivered linkage case management and treatment navigation services (CommLink) was more effective than peer-delivered counseling, referral, and telephone follow-up (standard linkage services, SLS) in initiating and retaining PLHIV on ART after diagnosis in community settings in Eswatini. HIV-test records of 773 CommLink and 769 SLS clients aged ≥ 15 years diagnosed between March 2016 and March 2018, matched by urban and rural settings of diagnosis, were selected for the study.

Discriminating between Waldenström macroglobulinemia and marginal zone lymphoma using logistic LASSO regression.

Discrimination between Waldenström macroglobulinemia (WM) and marginal zone lymphoma (MZL) of the bone marrow (BM) can be difficult due to overlap in clinical, histopathologic, and immunophenotypic characteristics. We determined which characteristics can aid in the differential diagnosis of 'gray zone' cases. We compared clinical, histopathologic, immunophenotypic, and molecular features of 222 WM and 65 MZL patients.

Forced Sexual Initiation and Early Sexual Debut and Associated Risk Factors and Health Problems Among Adolescent Girls and Young Women - Violence Against Children and Youth Surveys, Nine PEPFAR Countries, 2007-2018.

Adolescent girls and young women aged 13-24 years are disproportionately affected by HIV in sub-Saharan Africa (1), resulting from biologic, behavioral, and structural* factors, including violence. Girls in sub-Saharan Africa also experience sexual violence at higher rates than do boys (2), and women who experience intimate partner violence have 1.3-2.

Prevalence and prognostic value of and mutations in ocular adnexal large B-cell lymphoma: a reclassification of ocular adnexal large B-cell lymphoma.

Aims: To (1) reclassify ocular adnexal large B-cell lymphomas (OA-LBCLs) per 2016 WHO lymphoma classification and (2) determine the prevalence of and mutations and their association with clinical parameters among OA-LBCLs.

Methods: This study is a retrospective analysis of all OA-LBCLs diagnosed in Denmark between 1980 and 2018. Medical records and tissue samples were retrieved.

Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype.

Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare extranodal lymphoma subtype. This retrospective study elucidates the currently unknown genetic background of a large clinically well-annotated cohort of DLBCL with osseous localizations (O-DLBCL), including PB-DLBCL. A total of 103 patients with O-DLBCL were included and compared with 63 (extra)nodal non-osseous (NO)-DLBCLs with germinal center B-cell phenotype (NO-DLBCL-GCB).