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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 … ality 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, a …

AMBIsome Therapy Induction OptimisatioN (AMBITION): High Dose AmBisome for Cryptococcal Meningitis Induction Therapy in sub-Saharan Africa: Study Protocol for a Phase 3 Randomised Controlled Non-Inferiority Trial.

BACKGROUND: Cryptococcal meningitis (CM) is a major cause of mortality in HIV programmes in Africa despite increasing access to antiretrovir … III randomised controlled non-inferiority trial conducted in five countries in sub-Saharan Africa: Botswana, Malawi, South Africa, Uganda and Zimbabwe. The trial will compare CM induction therapy with (1) a single dose (10 mg/kg) of L-AmB given with 14 days of fluconazole (1200 mg/day) and flucytosine (100 mg/kg/day) to (2) seven days amphotericin B deoxy …

Is syndromic data from rural poultry farmers a viable poultry disease reporting tool and means of identifying likely farmer responses to poultry disease incursion?

Syndromic surveillance is a well described tool used in developed countries for alerting authorities to livestock disease incursions. Howeve … nly being used in Eastern Zambia, and which are also used to treat poultry diseases in Zimbabwe and Botswana. Only fourteen remedies described are conventionally accepted by veterinarians as remedies and disease control measures for poultry diseases. This study shows that syndromic data obtained from farmers is a useful disease reporting tool and could be …

HIV care cascade of adolescents and young adults in sub-Saharan Africa: a systematic review and meta-analysis.

OBJECTIVES: Tracking the progress of the Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 targets is essential for evaluating HI … for full-text screening and 37 were included. The studies originated from 13 (South Africa, Uganda, Botswana, Eswatini, Rwanda, Lesotho, Malawi, Cameroon, Democratic Republic of Congo, Ghana, Nigeria, Tanzania and Zimbabwe) SSA countries. The most reported age range 15-24 years (n=19, 51%). Half (n=18, 49%) of the studies reported one of three cascade outc …

Isoniazid for preventing tuberculosis in HIV-infected children.

BACKGROUND: Tuberculosis (TB) is an important cause of illness and death in HIV-positive children living in areas of high TB prevalence. We … included three trials, involving 991 participants, below the age of 13 years, from South Africa and Botswana. Children were randomized to isoniazid prophylaxis or placebo, given daily or three times weekly. The median length of follow-up ranged from 5.7 to 34 months; some were on antiretroviral therapy (ART).In HIV-positive children not on ART, isoniazid p …

Editorial: Rare hematological malignancies.

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… Acknowledgments PP is currently affiliated to the University of Nairobi (Nairobi, Kenya), and the University of Botswana (Gaborone, Botswana). Funding Statement The author(s) declare that no financial support was received for the research and/or publication of this article. …

Safety of combined long-acting injectable cabotegravir and long-acting injectable rilpivirine in virologically suppressed adolescents with HIV (IMPAACT 2017/MOCHA): a phase 1/2, multicentre, open-label, non-comparative, dose-finding study.

BACKGROUND: Long-acting cabotegravir and long-acting rilpivirine constitute a completely intramuscular antiretroviral therapy (ART) regimen for adults with HIV. We aimed to assess the safety, antiviral activity, and pharmacokinetics of oral cabotegravir and rilpivirine followed by a combination of long-acting cabotegravir and long-acting rilpivirine in virologically suppressed adolescents with HIV. METHODS: The IMPAACT 2017/MOCHA study is a phase 1/2, multicentre, open-label, non-comparative, dose-finding trial being conducted at 18 sites across Botswana, South Africa, Thailand, Uganda, and t…

Epstein-Barr virus and cytomegalovirus co-infections and mortality risk in patients with HIV-associated cryptococcal meningitis: a post-hoc analysis of a prospective nested cohort in the AMBITION-cm randomised controlled trial.

BACKGROUND: HIV-associated cryptococcal meningitis case fatality remains greater than 25%. Co-prevalent infections might contribute to poor … ON-cm randomised trial. AMBITION-cm was done at seven hospital sites across five African countries (Botswana, Malawi, South Africa, Uganda, and Zimbabwe). The primary endpoint of the trial was all-cause mortality at 10 weeks. Quantitative PCR (qPCR) was used to measure baseline cytomegalovirus and EBV viral loads in these samples. Baseline demographic and …

Early immunologic failure is associated with early mortality among advanced HIV-infected adults initiating antiretroviral therapy with active tuberculosis.

BACKGROUND: The relationship between antiretroviral therapy (ART) response and early mortality after ART initiation is unknown. We hypothesized that early mortality is associated with decreased early immunologic response to ART. METHODS: We prospectively determined the association between changes in plasma human immunodeficiency virus type 1 (HIV-1) RNA and CD4(+) T-cell counts (CD4 count) after 4 weeks of ART and early mortality in adults with pulmonary tuberculosis and pre-ART CD4 counts ≤ 125 cells/µL. Purified protein derivative (PPD)-specific immune recovery was determined by interferon-

Timing of maternal isoniazid preventive therapy on tuberculosis infection among infants exposed to HIV in low-income and middle-income settings: a secondary analysis of the TB APPRISE trial.

BACKGROUND: Infants born to women with HIV in settings with a high tuberculosis burden are at risk of tuberculosis infection and rapid progr … ble-blind, placebo-controlled, non-inferiority trial done at 13 study sites across eight countries (Botswana, Haiti, India, South Africa, Tanzania, Thailand, Uganda, and Zimbabwe). Pregnant women with HIV on antiretroviral therapy were randomly assigned to receive immediate isoniazid preventive therapy (28 weeks isoniazid [300 mg daily], then placebo until …

Robust Reconstitution of Tuberculosis-Specific Polyfunctional CD4+ T-Cell Responses and Rising Systemic Interleukin 6 in Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome.

BACKGROUND: The immunopathogenesis of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains unclear. We determined the association between pathogen-specific T-cell responses and development of paradoxical TB-IRIS on antiretroviral therapy (ART). METHODS: This study was nested within a prospective cohort study of HIV-infected patients with active pulmonary tuberculosis and baseline CD4 counts ≤125 cells/µL initiating ART. T-cell immune activation (CD38, HLA-DR, and PD-1 expression), phenotype, and polyfunctional pathogen-specific cellular immune resp

Dolutegravir and pregnancy outcomes including neural tube defects in the USA during 2008-20: a national cohort study.

BACKGROUND: A study from Botswana identified an increased risk of neural tube defects (NTDs) in infants of mothers with HIV who were treated with dolutegravir around the time of conception. We aimed to examine associations of dolutegravir use with NTDs and pregnancy loss using large health-care claims databases from the USA, a country with folic acid fortification of food. METHODS: In this cohort study, we analysed health-care claims data, recorded in the Merative MarketScan commercial database (MarketScan data) and Centers for Medicare & Medicaid Services Medicaid database (Medicaid data) fr…

Afri-Can Forum 2 : Johannesburg, South Africa. 16-18 February 2015.

A1 Introduction to the 2nd synchronicity forum of GHRI/CHVI-funded Canadian and African HIV prevention and vaccine teams O1 Voluntary medica … nts on a non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy in Botswana Thabo Diphoko, Simani Gaseitsiwe, Victoria Maiswe, Thato Iketleng, Dorcas Maruapula, Keabetswe Bedi, Sikhulile Moyo, Rosemary Musonda, Mark Wainberg, Joseph Makhema, Vladimir Novitsky, Richard Marlink, Max Essex O18 From home-based HIV testing to in …

Barriers to the Provision and Utilization of Palliative Care in Africa: A Rapid Scoping Review.

Palliative care (PC) has continued to be less available, underutilized, and unintegrated in many of the healthcare systems, especially in Africa. This scoping review synthesized existing published papers on adult PC in Africa, to report the barriers to PC and to assess the methodologies used in these studies. Eight electronic databases and Google Scholar were searched to identify relevant studies published between 2005 and 2018. Overall, 42 publications (34 empirical studies and 9 reviews) that reported issues related to barriers to adult PC were selected. Three themes identified were individu

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… Conversely, three studies found that majority of patients and their family members had no knowledge of, and were inadequately aware of, PC and hospice care services.[ 27 , 28 , 29 ] However, it was reported in the 2015 QOD that no public awareness or understanding of PC exists in Botswana.[ 1 ] Two studies … some aspects of PC while providing care to service users,[ 14 , 36 , 48 ] confirming what has been reported in the literature about the development of PC in Africa.[ 22 , 23 , 24 ] Findings across the previous review papers about PC consistently reported that countries such as South Africa, Uganda, Botswana …

Safety, antiviral activity, and pharmacokinetics of long-acting cabotegravir plus long-acting rilpivirine in virologically suppressed adolescents living with HIV-1 (IMPAACT 2017/MOCHA): week 96 and end-of-study results from a multinational, phase 1/2, single-arm trial.

BACKGROUND: Week 24 and week 48 study data from the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT 2017)/ … ars, weighing ≥35 kg) with HIV-1 who were virologically suppressed were enrolled across 18 sites in Botswana, South Africa, Thailand, Uganda, and the USA. Participants switched from pre-study antiretroviral therapy (ART) to 4 weeks of daily oral cabotegravir plus oral rilpivirine, followed by 600 mg long-acting cabotegravir plus 900 mg long-acting rilpivir …

Safety, antiviral activity, and pharmacokinetics of long-acting injectable cabotegravir-rilpivirine in virologically suppressed adolescents living with HIV-1 (IMPAACT 2017/MOCHA): 48-week results of a multinational, phase 1/2, single-arm study.

BACKGROUND: Combined intramuscular long-acting cabotegravir-rilpivirine is the first long-acting combination antiretroviral therapy regimen … DS: In this phase 1/2, open-label, non-comparative, dose-finding trial conducted at 18 sites across Botswana, South Africa, Thailand, Uganda, and the USA, virologically suppressed (HIV-1 RNA <50 copies per mL) adolescents (aged 12-17 years; weight ≥35 kg) with HIV-1 switched prestudy antiretrovirals to 4 weeks of daily oral 30 mg cabotegravir and 25 mg ril …

Phase I safety and immunogenicity evaluations of an alphavirus replicon HIV-1 subtype C gag vaccine in healthy HIV-1-uninfected adults.

On the basis of positive preclinical data, we evaluated the safety and immunogenicity of an alphavirus replicon HIV-1 subtype C gag vaccine (AVX101), expressing a nonmyristoylated form of Gag, in two double-blind, randomized, placebo-controlled clinical trials in healthy HIV-1-uninfected adults. Escalating doses of AVX101 or placebo were administered subcutaneously to participants in the United States and Southern Africa. Because of vaccine stability issues, the first trial was halted prior to completion of all dose levels and a second trial was implemented. The second trial was also stopped p

Defining the pathogenic threat of envenoming by South African shield-nosed and coral snakes (genus Aspidelaps), and revealing the likely efficacy of available antivenom.

While envenoming by the southern African shield-nosed or coral snakes (genus Aspidelaps) has caused fatalities, bites are uncommon. Conseque … s and several subspecies of potentially medically important venomous snakes distributed in Namibia, Botswana, Zimbabwe, Mozambique and South Africa. Documented human fatalities, although rare, have occurred from both A. lubricus and A. scutatus. However, their venom proteomes and the pathological effects of envenomings by this understudied group of nocturn …