Acceptability of a dapivirine levonorgestrel vaginal ring in two Phase 1 trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019): Implications for multipurpose prevention technology development.

End-user feedback early in product development is important for optimizing multipurpose prevention technologies for HIV and pregnancy prevention. We evaluated the acceptability of the 90-day dapivirine levonorgestrel ring (DPV-LNG ring) used for 14 days compared to a dapivirine-only ring (DVR-200mg) in MTN-030/IPM 041 (n = 23), and when used for 90 days cyclically or continuously in MTN-044/IPM 053/CCN019 (n = 25). We enrolled healthy, non-pregnant, HIV-negative women aged 18-45 in Pittsburgh, PA and Birmingham, AL (MTN-030 only).

Phase 1 randomized trials to assess safety, pharmacokinetics, and vaginal bleeding associated with use of extended duration dapivirine and levonorgestrel vaginal rings.

Background: Vaginal rings formulated to deliver two drugs simultaneously have potential as user-controlled, long-acting methods for dual prevention of HIV and pregnancy.

Methods: Two phase 1 randomized trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019) respectively enrolled 24 and 25 healthy, HIV-negative participants to evaluate safety, pharmacokinetics, and vaginal bleeding associated with use of a vaginal ring containing 200mg dapivirine (DPV) and 320mg levonorgestrel (LNG) designed for 90-day use. MTN-030/IPM 041 compared the DPV/LNG ring to a DPV-only ring (200mg) over 14 days of use.

Improving crop growing conditions with water treatment residual and compost co-amendments: Soil-water dynamics.

Land application of water treatment residual (WTR) in combination with phosphate-rich organic wastes, like compost or sewage sludge, in nutrient-poor soils was previously shown to promote crop growth. This WTR diversion from landfill to agriculture supports local and international mandates for waste circularity. Although soil-water dynamics-like saturated hydraulic conductivity, water retention, and hydrophobicity-are well-defined for compost and somewhat defined for WTR (except for hydrophobicity), the impacts of co-amending sandy soils with both are not well-defined.

Adherence, safety, and choice of the monthly dapivirine vaginal ring or oral emtricitabine plus tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis among African adolescent girls and young women: a randomised, open-label, crossover trial.

Background: Half of new HIV acquisitions in Africa occur in adolescent girls and young women. Pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate plus emtricitabine or the monthly dapivirine vaginal ring is efficacious but has lower adherence and effectiveness among adolescent girls and young women. We aimed to assess product adherence, safety, and choice of oral PrEP compared with the dapivirine ring among African adolescent girls and young women.

Characterization of Viruses in Phase 3 and Phase 3b Trials (the Ring Study and the Dapivirine Ring Extended Access and Monitoring Trial) of the Dapivirine Vaginal Ring for Human Immunodeficiency Virus Type 1 Infection Risk Reduction.

Background: The Ring Study demonstrated 35.1% human immunodeficiency virus type 1 (HIV-1) infection risk reduction among participants who used the Dapivirine vaginal ring-004 (DVR), whereas the Dapivirine Ring Extended Access and Monitoring (DREAM) trial, approximated a 62% risk reduction. The observed non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs) and effects on viral susceptibility are described here.

Clinical Presentation, Treatment Response, and Virology Outcomes of Women Who Seroconverted in the Dapivirine Vaginal Ring Trials-The Ring Study and DREAM.

Background: Participants with human immunodeficiency virus (HIV) seroconversion in The Ring Study, a phase 3 trial of dapivirine vaginal ring (DVR), or in the open-label extension trial dapivirine ring extended access and monitoring (DREAM) were offered enrollment in an observational cohort study (IPM 007) to assess clinical presentation and response to antiretroviral therapy (ART).

Methods: Participants' HIV infection was managed at local treatment clinics according to national treatment guidelines. IPM 007 study visits occurred 3 and 6 months after enrollment and every 6 months thereafter.

Phase 1 pharmacokinetics and safety study of extended duration dapivirine vaginal rings in the United States.

Introduction: Vaginal rings are a promising approach to provide a woman-centred, long-acting HIV prevention strategy. Prior trials of a 25 mg dapivirine (DPV) ring have shown a favourable safety profile and approximately 30% risk reduction of HIV-1 infection. Extended duration rings replaced every three months may encourage user adherence, improve health service efficiency and reduce cost overall.

Safety, adherence, and HIV-1 seroconversion among women using the dapivirine vaginal ring (DREAM): an open-label, extension study.

Background: The Ring Study, a phase 3 trial in 1959 sexually active women (randomised 2:1), showed a favourable safety profile and a 31% HIV-1 infection risk reduction for a vaginal ring containing 25 mg of dapivirine, compared with a placebo ring. We report here the DREAM study, which aimed to evaluate safety, adherence, and HIV-1 incidence in those using the dapivirine vaginal ring (DVR) in open-label use.

Methods: The DREAM study is an open-label extension of The Ring Study, done at five research centres in South Africa and one research centre in Uganda.

Analysis of Site Heterogeneity and HIV Outcomes Across Rural and Urban Study Sites in Phidisa II - A Multi-site Randomized Controlled Antiretroviral Treatment Trial in a South African Military Cohort.

Background: Clinical trials frequently enroll subjects from different study sites. Few such studies provide analysis by individual site. Between 2004-2007, the South African Military Health System (SAMHS) established 6 research sites (3 urban, 3 rural) to build capacity for clinical research and HIV care.

Safety and Efficacy of a Dapivirine Vaginal Ring for HIV Prevention in Women.

Background: The incidence of human immunodeficiency virus (HIV) infection remains high among women in sub-Saharan Africa. We evaluated the safety and efficacy of extended use of a vaginal ring containing dapivirine for the prevention of HIV infection in 1959 healthy, sexually active women, 18 to 45 years of age, from seven communities in South Africa and Uganda.

Methods: In this randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned participants in a 2:1 ratio to receive vaginal rings containing either 25 mg of dapivirine or placebo.

Detection of human herpes virus 8 DNA and sequence polymorphism in classical, epidemic, and iatrogenic Kaposi's sarcoma in South Africa.

The aetiology and detection of human herpes virus type 8 (HHV-8) DNA sequences in Kaposi's sarcoma (KS) is a matter of intense investigation. We report on the detection of HHV-8 DNA and sequence polymorphism in different clinicopathological subtypes of cutaneous KS samples from South Africa. The diagnosis was confirmed by histological examination in all cases.

Apoptotic megakaryocyte dysplasia in the myelodysplastic syndromes.

The terminal phase of the megakaryocyte life span is characterized by the onset of apoptosis to form compact, denuded megakaryocyte nuclei (DMK) surrounded by a thin rim of cytoplasm. Increased numbers of DMK have been reported in patients with acquired immune deficiency syndrome (AIDS) and chronic myeloproliferative disorders. In this study the bone marrow biopsies of 20 patients with various FAB subtypes of myelodysplastic syndrome (MDS) were examined for the presence of DMK cells and semiquantified for marrow reticulin level.

Mycotoxic peripheral myelinopathy, myopathy, and hepatitis caused by Diplodia maydis in vervet monkeys.

During recent historical times many Africans changed their diet to one based on maize. The grain is regularly contaminated by fungi which are toxigenic to domestic animals and birds. After one of the fungi, Diplodia maydis, in pure culture on maize, was added to the food of omnivorous primates there was demyelination of nerves, atrophy, degeneration and necrosis of muscle, and hepatitis.

Increased peripheral lymphocytes, lymphoid hepatitis and anaemia in African vervet monkeys seropositive to retroviruses.

Wild-caught African Vervet monkeys are commonly infected by Simian T-lymphotropic virus I (STLV1) and Simian immunodeficiency virus (SIV), yet the natural histories of these infections are largely unknown. Seropositivity was associated with increased total, T and atypical lymphocytes. In seropositive females there was mild, normocytic, normochromic anaemia.

Diets realistic for westernized people significantly effect lipoproteins, calcium, zinc, vitamins C, E, B6 and haematology in vervet monkeys.

This report describes measurements of 50 variables in adult, female, reproductively inactive Vervet monkeys during prolonged nutrition realistic for westernized people. Dietary treatments consisted of an atherogenic Western diet (WD) and a prudent Western diet (PD). Ingredients were normal foods for man and no extra cholesterol was added.

Hodgkin's disease and acute promyelocytic leukaemia. A case report.

A case of Hodgkin's disease is reported in which acute promyelocytic leukaemia developed within 5 months of initiation of chemotherapy. Only 3 other cases, possibly of a similar nature, were found in the literature; these had occurred 15, 77, and 226 months respectively after the initial diagnosis of Hodgkin's disease.

Clinical and haematological problems associated with severe abruptio placentae.

A clinical study was done of 80 patients in whom abruptio placentae was severe enough to cause intra-uterine death of the fetus. Central venous pressure pressure was measured when ever possible to ensure adequate fluid replacement. Although the minority of the patients were shocked when admitted, blood replacement averaged 5 units per patient.

[Myelopoiesis--a kinetic approach].

The mechanisms of haemopoietic cellular proliferation are more clearly understood when the granylocytic, monocytic and macrophagic elements of the bone marrow are studied by means of in vitro cultures. Better physiological insight into stimulating and inhibitory factors is obtained in this way. These studies are of diagnostic, therapeutic and prognostic importance in the clinical handling of myeloid leukaemia dn neutropenia.