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- ItemRestrictedCharacteristics and outcomes of HIV Patients starting ART in the era of routine screening for advanced HIV Disease at Lighthouse Trust, Lilongwe(Kamuzu University of Health Sciences, 2023-01-11) Buleya, ShameemType of Research Study This is a retrospective cohort study that will focus on exploring the characteristics and outcomes of HIV patients starting ART in the era of routine screening for advanced HIV diseases at Lighthouse Trust, Malawi. Problem statement The department of HIV/AIDS in Malawi implemented the Advanced HIV Disease (AHD) package of care in 2018 to reduce deaths in People living with HIV (PLHIV). AHD laboratory screening for tuberculosis and cryptococcal infection using CD4 count of ≤200 cells/ul as a cut-off point was since enforced on every newly HIV diagnosed client before starting ART. However, it has been observed that despite the implementation of the AHD package, there is limited data in Malawi on the proportion of people initiated on ART with AHD and their specification on age segregation. Subsequently, the effect of CD4 screening and testing for opportunistic infections on antiretroviral Treatment (ART) outcomes has not been well described in Malawi. This study will address the knowledge gap on distribution of AHD in people newly diagnosed with HIV will help program implementors introduce approaches to reduce the prevalence of AHD in the general HIV population of PLHIV. Objectives The broad objective of the study is to describe the epidemiology of clients diagnosed with AHD in the Era of Routine advanced HIV disease screening at Lighthouse Clinic- Lilongwe. The specific objectives are: i. To estimate the proportion of people with CD4 count of ≤200 cells/ul. ii. To determine the demographic characteristics of people starting ART with CD4 count of ≤200 cells/ul. iii. To assess the ART outcomes of clients diagnosed with AHD conditions at ART initiation. Methodology This is a quantitative study of retrospective cohort design which will be conducted at Lighthouse Trust, Lilongwe. The study population will include all HIV newly diagnosed patients started ART at Lighthouse Trust from October 2020 to September 2021, with a CD4 count result before initiation. A suitable anonymized purposive sample of one-year initiations will be selected from the Electronic Medical Records System (EMRS) and all study records meeting the inclusion criteria. Secondary data will be collected from laboratory equipment, registers and the lighthouse electronic medical record keeping system, which will be entered in a tailored data collection tool (appendix A). Data will be analyzed through regression analysis. Expected Findings The study expects to find the proportion of people starting ART with AHD using CD4 count as a marker as well as WHO HIV clinical staging. It will assess the characteristics of individuals presenting with AHD at initiation and their clinical outcomes over a year. For instance, it is anticipated that males of older age groups (above 50 years) have higher risk of developing AHD due to their poor health seeking behaviors. Patients who started ART with existing AHD are expected to have poorer clinical outcomes; weight loss, elevated HIV Viral Load copies at 6 months, and higher mortality rates than their counterparts with higher CD4 count. Dissemination of results Presentation of the outcomes shall be in tables, charts, and graphs, the research findings will be presented to College of Medicine Research ethics Committee (COMREC) as well as Lighthouse Trust clinic.
- ItemRestrictedImpact of HIV on risk of Treatment Resistant Hypertension in Malawian Adults (TREAM Study), version 1.0(2022-08-17) Gondwe, JacquelineType of research study Case – control study Problem to be studied Hypertension is a long-term condition with serious effects on the lives and well-being of individuals. Africa, a region that is significantly affected by the HIV pandemic, is experiencing a growing burden of non-communicable diseases such as hypertension. It is now known that HIV increases the risk of hypertension(1), which presents a significant burden on individuals and nations alike. Despite its high burden, most individuals suffering from hypertension do not achieve good blood pressure control. A common emerging cause of inadequate blood pressure control is treatment resistant hypertension(2). Treatment resistant hypertension (RH) is defined as uncontrolled blood pressure (≥140/90 mm Hg) despite treatment with ≥3 medications of different classes (including diuretics) at optimal doses. It is associated with significant risk of end organ damage (such as myocardial infarction, stroke, and impaired renal function). While some studies have quantified the burden of resistant hypertension in Africa, there is paucity of evidence regarding the association of resistant hypertension and HIV. This study seeks to determine the association of HIV and treatment resistant hypertension and investigate other modifiable factors that increase the risk of treatment resistant hypertension in Malawian adults. Objectives This research project seeks to investigate the association of HIV infection and treatment resistant hypertension and determine other modifiable risk factors of treatment resistant hypertension in Malawian adults. Specific objectives 1. To determine the association between HIV infection and RH in Malawian adults (primary objective) 2. To identify other modifiable risk factors associated with RH in Malawian adults (secondary objective) Methodology17-Aug-2022 Version 2 26 July 2022 5 Malawi-Liverpool-Wellcome Trust Clinical Research Programme P.O. Box 30096, Chichiri, Blantyre 3, Malawi Study population: Medical patients over 18years of age presenting to hypertension clinic at Queen Elizabeth Central Hospital Study place: Queen Elizabeth Central Hospital Study duration: 8 months Data management and analysis: Blood pressure will be measured using ambulatory blood pressure cuffs recorded over 6 hours. Weight and height will be measured using standard methods. Body mass index (BMI) will be calculated and categorized by age, sex and percentile. HIV rapid test, creatinine, and total cholesterol will also be measured through chemistry analysis of blood samples. The odds ratio for the association between HIV as well as the various modifiable risk factors and treatment resistant hypertension will be generated using statistical software such as Stata 16. Expected finding and dissemination: The results will provide some evidence of the association between HIV and treatment resistant hypertension, and predictors of the same. This knowledge will add to a larger body of work that is aimed to ascertain the true burden of resistant hypertension in Malawi. Knowing the risk factors will aid in early detection and subsequent control of the risk factors. The results of the study will be disseminated to study participants and through a peer reviewed scientific journal. Additionally, a final report of this study and findings will be submitted to the College of Medicine Research and Ethics Committee (COMREC).
- ItemRestrictedAn analysis of enteric pathogens among HIV infected individuals with and without diarrhea at Queen Elizabeth Central Hospital(Kamuzu University of Health Sciences, 2022-08-17) Nyirenda, JamesEastern and Southern Africa bears the blunt of the Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Virus Syndrome (AIDS) pandemic having about 54% of world’s HIV/AIDS infected individuals coming from this region. Diarrhea is one of the most common complications of HIV with 80% of all HIV/AIDS infected individuals developing this condition. There is an association between CD4+ T cell count and presence of opportunistic infections. Management of diarrhea in developing countries including Malawi depends on empirical administration of drugs, mostly antibiotics. This is often times due to lack of proper diagnostic capability to determine full profile of enteric pathogens that are likely to contribute to diarrhea for particular patients. Objective: To identify and determine entero-pathogens which are likely contributors of diarrhea among HIV infected individuals in Malawi. Specific Objectives: Determine the profile of enteric pathogens across HIV infected individual with and without diarrhea. To identify pathogens detected in diarrheagenic amounts among HIV infected individuals with and without diarrhea. To determine if the antibiotic prescribing pattern among clinicians covers enteropathogens detected using TaqMan array card. To determine if there is an association between CD4 T cell count and type of pathogens detected in HIV positive individuals with and without diarrhea. Methods: This study will be nested in a phase 2A clinical Trial investigating the safety and efficacy of Clofazimine for treatment of Cryptosporidiosis among HIV+ adults. Two arms of study participants will be used to answer our questions; 22 HIV infected individuals with diarrhea and 10 infected individuals without diarrhea. TaqMan array based polymerase chain reaction (PCR) was used to detect multiple enteric pathogens from stool samples in the main study. In this study threshold cycle (Ct) values and pathogens detected from each group will be analyzed and used to determine the mostly likely pathogen contributing or causing diarrhea. In addition CD4 T cell values and profile of identified entero-pathogens will be analyzed to determine if level of an individual’s immunity plays a role in profile of enteric pathogens among HIV infected individuals. Furthermore, antibiotics that were administered to manage diarrhea will be analyzed to determine whether it necessary for treating the type of pathogens detected. Study Place: Data analysis and investigations will be conducted at the College of Medicine Department of Pathology and college of medicine Library. Expected outcome: We expect to identify enteric pathogens that are more likely than others to contribute to diarrhea among HIV infected individuals. We will identify pathogens and make profile of pathogens in relation to CD4 T cell values. This data will be essential for policy formulation for management of diarrhea in HIV infected adults since treatment is mostly empirical in developing countries such as Malawi due to poor diagnostic capacity.
- ItemRestrictedDeveloping “U=U” communication messages targeting HIV discordant couples in Malawi: Establishing evidence on feasibility and acceptability(2022-07-20) Kumwenda, MosesThis research will employ a mixed-methods approach combining qualitative and quantitative approaches to develop and pilot “Undetectable = Untransmittable” in short “U=U” communication materials that could be delivered through ANC clinics in Blantyre, Malawi. The problem There is a gap in evidence on the availability of “U=U” communication materials in Malawi and information on how HIV sero-discordant couples who are expecting a baby can manage their HIV status to minimise the probability of transmitting HIV virus to the partner or the infant. This gap needs to be filled to enable policy makers and implementers in Malawi to make informed choices on how “U=U” communication material can be integrated within the ANC care and HIV programme in Malawi. The Objectives The broad aim is to develop contextually relevant TasP messaging materials that emphasise “U=U” information targeting HIV discordant couples. The specific objectives are to: 1. To explore understanding of TasP and “U=U” among HIV-discordant couples and recipients of ART care. 2. To develop culturally relevant communication materials that optimise user comprehension of “U=U” concepts targeting HIV sero-discordant heterosexual couples . 3. To test the acceptability of the developed “U=U” messages targeting HIV discordant couples. Methodology20-Jul-2022 ACCEPT ‘U=U’ Study - PROTOCOL Version 3.0: 15/04/2021 Page 5 of 36 This is a mixed-methods study that will develop and pilot “U=U” communication materials delivered through ANC clinics of Bangwe, Limbe, Madziabango and Mpemba Health Centres antenatal clinic in Blantyre, Malawi. Focus group discussion and key informant interviews will be done during the formative qualitative investigation. Three stakeholder participatory workshop and cognitive interviews will be used during the “U=U” communication material development stage. A Phase 2 exploratory trial will be done at Bangwe, Limbe, Madziabango and Mpemba Health Centres to test the feasibility and acceptability of the developed “U=U” communication materials. Expected findings and dissemination Expected results from this study include well developed and contextualised “U=U” messages, and outcomes following a pilot test of the application of “U=U” messages within primary health care context in Malawi. The results of this research will be used to guide the formation of national and international policies. Findings will be circulated to the College of Medicine Research and Ethics Committee, the Health Sciences Research Committee and the University Research and Publication Committee. Results will also be distributed to global health policy makers, nationally to the Malawian government, including HTS technical working group. Research findings will be published in journals and presented at conference.s
- ItemRestrictedSame-day versus rapid ART initiation in HIV-positive individuals presenting with symptoms of tuberculosis: an open-label randomized non-inferiority trial in Lesotho and Malawi (SaDAPT)(Kamuzu University of Health Sciences, 2022-06-06) Nliwasa, MarriotSponsor-Investigator Prof. Dr. Niklaus Labhardt, MD, DTM&H, MIH Swiss Tropical and Public Health Institute & University Hospital Basel Study Title: Same-day versus rapid ART initiation in HIV-positive individuals presenting with symptoms of tuberculosis: an open-label, randomized, controlled clinical trial in Lesotho and Malawi Short Title / Study ID: SaDAPT Trial (“Same-Day ART initiation in Presumptive TB”) Protocol Version and Date: Version 2.0, 05.06.2022 Trial registration: Registration is planned on clinicaltrials.gov as soon as this version of the protocol has been approved by the Independent Ethics Committees (IECs) Study category and Rationale Risk category A. The SaDAPT trial entails the comparison of two different algorithms for the timing of ART initiation in people living with HIV (PLHIV) presenting with symptoms of a possible tuberculosis (TB) infection but no signs of central nervous system (CNS) disease. Both approaches are in line with current national or international guidelines. Clinical Phase: Therapeutic use trial. The trial uses treatments and drug-doses as per international and national guidelines. All treatment components will be applied at standard dosage and no new substances or alternative indications will be tested. Background and Rationale HIV remains a major cause of morbidity and premature death in many sub-Saharan African countries including Lesotho and Malawi. Globally, 680’000 lives were lost in 2020 in association with HIV despite the availability of effective and low-cost antiretroviral therapy (ART).1 The most important opportunistic infection associated with HIV is TB, accounting for over 200’000 HIV-related deaths worldwide, mainly in low-income settings, where prevalence of HIV/TB-coinfection is highest.2 WHO recommends a four-symptom screening (W4SS) approach including cough, fever, night sweat and weight loss for clinical routine TB screening among PLHIV. 3–6 PLHIV presenting with at least one of the four symptoms are defined as having presumptive TB. The prevalence of presumptive TB among PLHIV not taking ART has been estimated at 71% in a systematic review. 4 An important approach to improve access to ART—and thereby reduce HIV transmission as well as AIDS related morbidity and mortality—is the implementation of rapid, and if possible same-day initiation (SDI) of ART.7 PLHIV with opportunistic infections may benefit particularly from rapid ART initiation and the subsequent suppression of HIV replication and reconstitution of CD4-cell mediated immunity. At the same time, they are at risk of developing immune reconstitution inflammatory syndrome (IRIS) after initiation of ART.8–10 The risk for development of IRIS increases with earlier initiation of ART.8,10–13 Until the release of a guideline update in 2021,3,14 WHO had recommended to delay initiation of ART in case of presumptive TB until TB has been investigated and TB treatment initiated if TB disease has been confirmed in order to reduce the risk of IRIS.15 The 2021 guideline update contains for the first time a “clinical consideration” to start ART in PLHIV with presumptive TB but no signs of central nervous system (CNS) disease while rapidly investigating for TB, thus allowing SDI for this subgroup of PLHIV. However, a systematic review on the effect of SDI for PLHIV with presumptive TB but no signs of CNS disease, that was conducted to inform this guideline update came to the conclusion that “there is insufficient evidence about whether presence of TB symptoms should lead to ART start being deferred or not”.16 Accordingly, the guidelines emphasize the need for further research on the impact of SDI in PLHIV with presumptive TB on various health outcomes including mortality, HIV and TB outcomes, retention in care, adverse events and IRIS.14 Overall objective: To compare two approaches for the timing of ART initiation in PLHIV with presumptive TB but no signs of CNS disease (“ART first” versus “TB results first”) with regard to HIV viral suppression, engagement in care, serious adverse events (SAEs) and adverse events (AEs) consistent with TB-IRIS in a pragmatic randomized trial reflecting routine primary and secondary care setting in southern Africa. Hypothesis For PLHIV with presumptive TB, but no signs of CNS disease, same day ART (“ART first”) is non-inferior to rapid ART (“TB results first”) for being retained in care with suppressed HIV viral load (VL) 26 weeks after enrolment. Endpoints: Primary endpoint - HIV viral suppression (VL <400 copies/mL) 26 (range 22 – 40) weeks after enrolment Secondary and safety endpoints - Retention in care 26 (22 – 30) weeks after enrolment - Engagement in care 26 (22 – 30) weeks after enrolment - Disengagement from care 26 (22 – 30) weeks after enrolment - Lost to follow-up 26 (22 – 30) weeks after enrolment - Non-traumatic mortality, Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs) during the first 30 weeks after enrolment - Incidence of TB disease (microbiologically confirmed and/or clinical diagnosis) during the first 30 weeks after enrolment - HIV viral suppression at 26 (22 – 40) weeks using different thresholds (<20 copies/mL; <100 copies/mL; <1000 copies/mL) - ART initiation within 7 and within 28 days after enrolment Study design: Prospective, parallel, open-label, 1:1 individually randomized, non-inferiority trial Inclusion / Exclusion criteria: Inclusion criteria - 12 years or older - HIV-positive - Not taking ART (naïve or reported no ART intake since 90 days or more) - Presenting with one or more TB symptoms according to W4SS4 - Planning to continue care at the study facility for at least 30 weeks - Willing and able to consent (age 18 years or older) or assent with guardian consent (age 12 to 17 years) Exclusion criteria - Medical condition requiring admission or referral to a higher level health facility at enrolment - Symptoms or clinical signs suggestive for diseases of the CNS - Positive cryptococcal antigen test (CrAg) - Reporting to be pregnant - Taking TB treatment or TB preventive therapy (TPT) ART initiators cohort In parallel to the the SaDAPT trial, we will observationally follow-up all PLHIV (re)initiating ART at the study sites in a prospective ART initiation cohort, independent of whether they are eligible for participation in the SaDAPT trial.