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BACKGROUND: The association between low-frequency human immunodeficiency virus type 1 (HIV-1) drug resistance mutations (DRMs) and treatment failure (TF) is controversial. We explore this association using next-generation sequencing (NGS) methods that accurately sample low-frequency DRMs. METHODS: We enrolled women with HIV-1 in Malawi who were either antiretroviral therapy (ART) naive (cohort A), had ART failure (cohort B), or had discontinued ART (cohort C). At entry, cohorts A and C began a nonnucleoside reverse transcriptase inhibitor-based regimen and cohort B started a protease inhibitor-based regimen. We used Primer ID MiSeq to identify regimen-relevant DRMs in entry and TF plasma samples, and a Cox proportional hazards model to calculate hazard ratios (HRs) for entry DRMs. Low-frequency DRMs were defined as ≤20%. RESULTS: We sequenced 360 participants. Cohort B and C participants were more likely to have TF than cohort A participants. The presence of K103N at entry significantly increased TF risk among A and C participants at both high and low frequency, with HRs of 3.12 (95% confidence interval [CI], 1.58-6.18) and 2.38 (95% CI, 1.00-5.67), respectively. At TF, 45% of participants showed selection of DRMs while in the remaining participants there was an apparent lack of selective pressure from ART. CONCLUSIONS: Using accurate NGS for DRM detection may benefit an additional 10% of patients by identifying low-frequency K103N mutations.
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Farmacorresistência Viral , Infecções por HIV , HIV-1 , Mutação , Falha de Tratamento , Humanos , HIV-1/genética , HIV-1/efeitos dos fármacos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Farmacorresistência Viral/genética , Adulto , Malaui , Fármacos Anti-HIV/uso terapêutico , Sequenciamento de Nucleotídeos em Larga Escala , Estudos de Coortes , Adulto Jovem , Resultado do TratamentoRESUMO
Blood and blood products are listed as one of the essential medicines by the World Health Organization (WHO). In addition to inadequate supply, most sub-Saharan Africa (SSA) nations fail to meet their blood needs because many donated blood units are discarded because they are contaminated with transfusion-transmitted infections (TTIs). We sought to estimate the prevalence of TTIs, identify the risk factors for TTIs among blood donors, and identify the efforts and interventions that have been made to improve blood safety in Southern African nations, particularly the nations of the South African Development Community (SADC). We investigated the prevalence and risk factors for TTIs, blood safety interventions, and blood quality improvement in the SADC region from major PubMed/MEDLINE, Cochrane Library, and HINARI databases from 1 January 2011 to 31 April 2021. All investigations followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). In meta-analysis, we estimated the pooled TTIs prevalence and summarised the same using forest plots. A total of 180 articles published from the SSA region were identified covering our three targeted themes: TTI prevalence, risk factors for TTIs, and blood safety improvements. Of these 180 articles, only 27 (15%) focused on the SADC region. The overall pooled TTI prevalence estimate was 2.0% (95% CI: 1.0-3.0) and hepatitis B was the most prevalent TTI in the region (prevalence = 3.0; 95% CI: 2.0-5.0). The prevalence of HIV, HCV, and syphilis was 2.0% (95% CI: 1.0-4.0), 1.0% (95% CI: 0.0-2.0), and 2.0% (95% CI: 0.0-8.0), respectively. In general, replacement donors and first-time donors were more likely to be infected with TTIs than repeat donors. Twelve articles explored blood safety research in the region; however, they vary greatly highlighting the need for consistent and more comprehensive research. Few publications were identified that were from the SADC region, indicating lack of research or resources towards improving both quantity and quality of blood donation. TTI prevalence remains one of the highest in the world and blood safety recommendations vary across the region. More effort should be directed towards developing a cohesive regional blood transfusion policy and effective blood monitoring and evaluation strategies.
RESUMO
BACKGROUND: Voluntary non-remunerated blood donors (VNRBDs) are essential to sustain national blood supplies. Expanding testing capacity for the major transfusion-transmitted infections (TTI) is crucial to ensure safe blood products. Understanding trends in TTIs can inform prioritisation of resources. METHODS: We conducted a retrospective cohort data analysis of routine blood donation data collected from VNRBDs by the Malawi Blood Transfusion Service from January 2015 to October 2021. Variables included age, occupation; and screening results of TTIs (HIV, Hepatitis B and C, and syphilis). We estimated both prevalence and incidence per person-year for each TTI using longitudinal and spatial logistic regression models. RESULTS: Of the 213 626 donors, 204 920 (95.8%) donors were included in the final analysis. Most donors (77.4%) were males, baseline median age was 19.9 (IQR 18.0, 24.1), 70.9% were students, and over 80.0% were single at first donation. Overall TTI prevalence among donors was 10.7%, with HBV having the highest prevalence (3.4%), followed by syphilis (3.3%), then HIV (2.4%) and HCV (2.4%). Incidence per 1000 person-years for syphilis was 20.1 (19.0, 21.3), HCV was 18.4 (17.3, 19.5), HBV was 13.7 (12.8, 14.7), and HIV was 11.4 (10.6, 12.3). We noted geographical variations with the northern region having lower rates of both prevalence and incidence compared to central and southern regions. CONCLUSION: The individual TTI prevalence and incidence rates from this study are consistent with Southern African regional estimates. By identifying geographical variations of TTI prevalence and incidence, these findings could potentially inform prioritisation of blood collection efforts to optimise blood collection processes.
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Infecções por HIV , Hepatite B , Hepatite C , Sífilis , Reação Transfusional , Masculino , Humanos , Adulto Jovem , Adulto , Feminino , Sífilis/epidemiologia , Incidência , Doadores de Sangue , Prevalência , Estudos Retrospectivos , Malaui/epidemiologia , Transfusão de Sangue , Reação Transfusional/epidemiologia , Hepatite B/epidemiologia , Hepatite C/epidemiologiaRESUMO
INTRODUCTION: In 2018, the Malawi Ministry of Health adopted the recommendation to switch first-line antiretroviral therapy (ART) from an efavirenz (EFV)-based to a dolutegravir (DTG)-based regimen. Little is known about patients' experience during this transition. We conducted a qualitative study to explore DTG-related counselling challenges among providers of HIV care and factors influencing regimen switching or non-switching among women living with HIV in Lilongwe, Malawi. METHODS: Between February-July 2020, we recruited participants who took part in DTG counselling on reasons to switch, side effects, and benefits from two government health facilities providing HIV care: Area 18 health centre and Bwaila district hospital in Lilongwe, Malawi. We purposively sampled and interviewed 8 women living with HIV who remained on an EFV-based regimen after counselling, 10 women who switched to a DTG-based regimen, and 10 HIV care providers who provided counselling about ART switching. In-depth interviews were used to explore patient's perceptions of DTG, factors affecting the decision to switch, and both patient and provider experience with counselling. Interview data was coded for themes using inductive and deductive codes. Interviews were conducted until thematic saturation was achieved. Data matrices were used for analysis and thematic extraction. RESULTS: Most women in both groups were well versed on DTG's potential side effects and felt well counselled on the benefits of switching, such as quicker viral load suppression. Many women associated DTG with birth defects and expressed concern. However, the primary reason for not switching was concern with how the new medication would be tolerated, especially when they were satisfied with their current regimen. Almost all providers expressed difficulty providing DTG counselling. Primary reasons included feeling inadequately trained and/or not having resources to use during counselling, such as diagrams or brochures. CONCLUSION: DTG counselling was well accepted by women; however, some felt that their concerns were not fully addressed. Providers reflected this sentiment in that they did not feel adequately trained or well-equipped to provide adequate counselling. Training on counselling for new ART regimens should be intensified and utilize patient-centered educational materials to address the concerns raised by both patients and health care providers.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Infecções por HIV , Humanos , Feminino , Benzoxazinas , Aconselhamento , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológicoRESUMO
INTRODUCTION: Antiretroviral therapy (ART) is very effective in preventing vertical transmission of HIV but some women on ART experience different virologic, immunologic, and safety profiles. While most pregnant women are closely monitored for short-term effects of ART during pregnancy, few women receive similar attention beyond pregnancy. We aimed to assess retention in care and clinical and laboratory-confirmed outcomes over 3 years after starting ART under Malawi's Option B + program. METHODS: We conducted a prospective cohort study of pregnant women newly diagnosed with HIV who started tenofovir disoproxil fumarate/emtricitabine/efavirenz (TDF/3TC/EFV) for the first time at Bwaila Hospital in Lilongwe, Malawi between May 2015 and June 2016. Participants were followed for 3 years. We summarized demographic characteristics, pregnancy outcomes, and clinical and laboratory adverse events findings using proportions. Log-binomial regression models were used to estimate the overall risk ratios (RR) and the corresponding 95% confidence interval (CI) for the association between index pregnancy (i.e. index pregnancy vs. subsequent pregnancy) and preterm birth, and index pregnancy and low birthweight. RESULTS: Of the 299 pregnant women who were enrolled in the study, 255 (85.3%) were retained in care. There were 340 total pregnancies with known outcomes during the 36-month study period, 280 index pregnancies, and 60 subsequent pregnancies. The risks of delivering preterm (9.5% for index pregnancy and13.5% for subsequent pregnancy: RR = 0.70; 95% CI: 0.32-1.54), or low birth weight infant (9.8% for index pregnancy and 4.2% for subsequent pregnancy: RR = 2.36; 95% CI: 0.58-9.66) were similar between index and subsequent pregnancies. Perinatally acquired HIV was diagnosed in 6 (2.3%) infants from index pregnancies and none from subsequent pregnancies. A total of 50 (16.7%) women had at least one new clinical adverse event and 109 (36.5%) women had at least one incident abnormal laboratory finding. Twenty-two (7.3%) women switched to second line ART: of these 64.7% (8/17) had suppressed viral load and 54.9% (6/17) had undetectable viral load at 36 months. CONCLUSION: Most of the women who started TDF/3TC/EFV were retained in care and few infants were diagnosed with perinatally acquired HIV. Despite switching, women who switched to second line therapy continued to have higher viral loads suggesting that additional factors beyond TDF/3TC/EFV failure may have contributed to the switch. Ongoing support during the postpartum period is necessary to ensure retention in care and prevention of vertical transmission.
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Infecções por HIV , Nascimento Prematuro , Recém-Nascido , Gravidez , Lactente , Feminino , Humanos , Masculino , Malaui , Estudos Prospectivos , TenofovirRESUMO
BACKGROUND: Cryptococcal meningitis (CM) and tuberculosis (TB) remain leading causes of hospitalization and death amongst people living with HIV, particularly those with advanced HIV disease. In hospitalized patients, prompt diagnosis of these diseases may improve patient outcomes. The advanced HIV rapid diagnostic tests such as determine TB urine lipoarabinomannan lateral flow assay (urine LAM), urine X-pert MTB/RIF assay (urine X-pert), and serum/blood cryptococcal antigen test (serum CrAg) are recommended but frequently not available in many resource-limited settings. We describe our experience providing these tests in a routine hospital setting. METHOD: From 1 August 2016 to 31 January 2017, a prospective cohort study to diagnose TB and Cryptococcal meningitis using point of care tests was conducted in the medical wards at Kamuzu Central Hospital, in Lilongwe, Malawi. The tests offered were PIMA CD4 cell count, serum CrAg, urine LAM, and urine X-pert. The testing was integrated into an existing HIV/TB treatment room on the wards and performed close to admission time. Patients were followed until discharge or death in the ward. RESULTS: We included 438 HIV-positive patients; 76% had a previously known HIV diagnosis (87% already on ART). We measured CD4 count in 365/438 (83%), serum CrAg in 301/438 (69%), urine LAM in 363/438 (83%), and urine X-pert in 292/438 (67%). The median CD4 count was 144 cells/ml (IQR 46-307). Serum CrAg positivity rate was 23 /301 (8%) and CM was confirmed by CSF Crag in 13/23 (56%). The majority of CM patients 9/13 (69%) started antifungal therapy within two days of diagnosis. Urine LAM and urine X-pert positivity rates were 81/363(22%) and (14/292 (5%) respectively. The positivity rate of urine LAM was higher in patients with low CD4 cell counts (< 100 cells/ml) and low BMI (< 18.5). Most patients with positive urine LAM started TB treatment on the same day. Despite the early diagnosis and treatment of TB and CM, the inpatient mortality was high; 30% and 25% respectively. CONCLUSION: Although advanced HIV rapid diagnostic tests are recommended, one key challenge in implementation is the limited trained personnel administering the tests. Despite the effective use of the point of care tests in the clinical care of hospitalized TB and CM patients, mortality among these patients remained unacceptably high. Henceforth we need to train other cadres apart from nurses, clinicians, and laboratory technicians to conduct the tests. There is an urgent need to identify and modify other risks of death from TB and CM. TRIAL REGISTRATION: Malawi National Health Science Research committee: Protocol # 1144. Registered 2 July 2014 and University Of North Carolina IRB #: UNCPM 21412, approved 13th October 2014.
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Infecções por HIV , Meningite Criptocócica , Tuberculose , Testes Diagnósticos de Rotina , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Hospitais , Humanos , Lipopolissacarídeos/urina , Malaui , Meningite Criptocócica/diagnóstico , Estudos Prospectivos , Sensibilidade e Especificidade , Tuberculose/diagnósticoRESUMO
BACKGROUND: In sub-Saharan Africa, 3 community-facility linkage (CFL) models-Expert Clients, Community Health Workers (CHWs), and Mentor Mothers-have been widely implemented to support pregnant and breastfeeding women (PBFW) living with HIV and their infants to access and sustain care for prevention of mother-to-child transmission of HIV (PMTCT), yet their comparative impact under real-world conditions is poorly understood. METHODS AND FINDINGS: We sought to estimate the effects of CFL models on a primary outcome of maternal loss to follow-up (LTFU), and secondary outcomes of maternal longitudinal viral suppression and infant "poor outcome" (encompassing documented HIV-positive test result, LTFU, or death), in Malawi's PMTCT/ART program. We sampled 30 of 42 high-volume health facilities ("sites") in 5 Malawi districts for study inclusion. At each site, we reviewed medical records for all newly HIV-diagnosed PBFW entering the PMTCT program between July 1, 2016 and June 30, 2017, and, for pregnancies resulting in live births, their HIV-exposed infants, yielding 2,589 potentially eligible mother-infant pairs. Of these, 2,049 (79.1%) had an available HIV treatment record and formed the study cohort. A randomly selected subset of 817 (40.0%) cohort members underwent a field survey, consisting of a questionnaire and HIV biomarker assessment. Survey responses and biomarker results were used to impute CFL model exposure, maternal viral load, and early infant diagnosis (EID) outcomes for those missing these measures to enrich data in the larger cohort. We applied sampling weights in all statistical analyses to account for the differing proportions of facilities sampled by district. Of the 2,049 mother-infant pairs analyzed, 62.2% enrolled in PMTCT at a primary health center, at which time 43.7% of PBFW were ≤24 years old, and 778 (38.0%) received the Expert Client model, 640 (31.2%) the CHW model, 345 (16.8%) the Mentor Mother model, 192 (9.4%) ≥2 models, and 94 (4.6%) no model. Maternal LTFU varied by model, with LTFU being more likely among Mentor Mother model recipients (adjusted hazard ratio [aHR]: 1.45; 95% confidence interval [CI]: 1.14, 1.84; p = 0.003) than Expert Client recipients. Over 2 years from HIV diagnosis, PBFW supported by CHWs spent 14.3% (95% CI: 2.6%, 26.1%; p = 0.02) more days in an optimal state of antiretroviral therapy (ART) retention with viral suppression than women supported by Expert Clients. Infants receiving the Mentor Mother model (aHR: 1.24, 95% CI: 1.01, 1.52; p = 0.04) and ≥2 models (aHR: 1.44, 95% CI: 1.20, 1.74; p < 0.001) were more likely to undergo EID testing by age 6 months than infants supported by Expert Clients. Infants receiving the CHW and Mentor Mother models were 1.15 (95% CI: 0.80, 1.67; p = 0.44) and 0.84 (95% CI: 0.50, 1.42; p = 0.51) times as likely, respectively, to experience a poor outcome by 1 year than those supported by Expert Clients, but not significantly so. Study limitations include possible residual confounding, which may lead to inaccurate conclusions about the impacts of CFL models, uncertain generalizability of findings to other settings, and missing infant medical record data that limited the precision of infant outcome measurement. CONCLUSIONS: In this descriptive study, we observed widespread reach of CFL models in Malawi, with favorable maternal outcomes in the CHW model and greater infant EID testing uptake in the Mentor Mother model. Our findings point to important differences in maternal and infant HIV outcomes by CFL model along the PMTCT continuum and suggest future opportunities to identify key features of CFL models driving these outcome differences.
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Serviços de Saúde Comunitária , Infecções por HIV/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Aleitamento Materno , Agentes Comunitários de Saúde , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/mortalidade , Infecções por HIV/transmissão , Humanos , Recém-Nascido , Nascido Vivo , Malaui , Mentores , Cooperação do Paciente , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/mortalidade , Avaliação de Programas e Projetos de Saúde , Medição de Risco , Fatores de Risco , Fatores de Tempo , Carga ViralRESUMO
ABSTRACT: Monitoring the burden of and trends in sexually transmitted infection syndromes is useful in informing syndromic management guidelines. Among sexually transmitted infection clinic patients in Lilongwe, Malawi, between 2006 and 2015, genital discharge, lower abdominal pain, and genital ulcer syndromes were common. Prevalence of most syndromes remained stable during the 10-year period.
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Infecções Sexualmente Transmissíveis , Humanos , Malaui/epidemiologia , Prevalência , Infecções Sexualmente Transmissíveis/epidemiologia , Síndrome , ÚlceraRESUMO
PURPOSE OF REVIEW: The relationship between antiretroviral therapy (ART) and cancer treatment outcomes among people living with HIV (PLWH) in low- and middle-income countries (LMICs) is complex and poorly understood for many cancers. We aimed to summarize existing evidence from LMICs regarding the benefit of ART on cancer treatment-related outcomes. RECENT FINDINGS: We included twelve observational studies that reported associations between ART status and cancer treatment outcomes among HIV-positive patients in LMICs. Most confirmed ART was associated with improved cancer treatment outcomes. Heterogeneity in cancers under study, outcome measurement, categorization of ART status, and reporting of HIV-related immune function made formal comparison between studies untenable. Where evaluated, ART generally has a positive effect on cancer outcomes in people with HIV in LMICs. However, there remains a substantial gap in the literature regarding the impact of ART on treatment outcomes for most cancer types. Future research should focus on the optimal timing and integration of ART and cancer treatment for PLWH with strategies applicable to constrained-resource settings.
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Fármacos Anti-HIV , Infecções por HIV , Neoplasias , Fármacos Anti-HIV/uso terapêutico , Países em Desenvolvimento , Infecções por HIV/tratamento farmacológico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Pobreza , Resultado do TratamentoRESUMO
BACKGROUND: Breast cancer incidence in sub-Saharan Africa (SSA) is increasing, and SSA has the highest age-standardized breast cancer mortality rate worldwide. However, high-quality breast cancer data are limited in SSA. MATERIALS AND METHODS: We examined breast cancer patient and tumor characteristics among women in Lilongwe, Malawi and evaluated risk factor associations with patient outcomes. We consecutively enrolled 100 women ≥ 18 years with newly diagnosed, pathologically confirmed breast cancer into a prospective longitudinal cohort with systematically assessed demographic data, HIV status, and clinical characteristics. Tumor subtypes were further determined by immunohistochemistry, overall survival (OS) was estimated using Kaplan-Meier methods, and hazards ratios (HR) were calculated by Cox proportional hazard analyses. RESULTS: Of the 100 participants, median age was 49 years, 19 were HIV-positive, and 75 presented with late stage (III/IV) disease. HER2-enriched and triple-negative/basal-like subtypes represented 17% and 25% tumors, respectively. One-year OS for the cohort was 74% (95% CI 62-83%). Multivariable analyses revealed mortality was associated with HIV (HR, 5.15; 95% CI 1.58-16.76; p = 0.006), stage IV disease (HR, 8.86; 95% CI 1.07-73.25; p = 0.043), and HER2-enriched (HR, 7.46; 95% CI 1.21-46.07; p = 0.031), and triple-negative subtypes (HR, 7.80; 95% CI 1.39-43.69; p = 0.020). CONCLUSION: Late stage presentation, HER2-enriched and triple-negative subtypes, and HIV coinfection were overrepresented in our cohort relative to resource-rich settings and were associated with mortality. These findings highlight robust opportunities for population- and patient-level interventions across the entire cascade of care to improve breast cancer outcomes in low-income countries in SSA.
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Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Infecções por HIV/epidemiologia , Humanos , Imuno-Histoquímica , Incidência , Estudos Longitudinais , Malaui/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Prioritizing HIV prevention for adolescent girls and young women (AGYW) at high risk for HIV acquisition in sub-Saharan Africa (typically considered ≥3 per 100 person-years [PYs]) is urgently needed, but identifying these AGYW is challenging. We sought to assess and, if needed, enhance a risk assessment tool from the VOICE trial for identifying AGYW at high risk for HIV in Lilongwe, Malawi. METHODS: A multisite prospective cohort study was conducted among sexually active AGYW 15 to 24 years old at 4 health centers in 2016 to 2017. The VOICE tool was first applied and then updated by excluding variables that were not predictive and adding variables that were. Incidence rates (IRs), incidence rate ratios, 95% confidence intervals (CIs), area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were calculated. RESULTS: Seven hundred ninety-five participants experienced 14 seroconversions for 672 PYs (IR, 2.08 per 100 PYs; 95% CI, 1.23-3.52). The VOICE tool had moderate predictive ability (AUC, 0.64; 95% CI, 0.52-0.75). Maintaining 2 variables (genital ulcers and vaginal discharge), removing 5 sociodemographic variables, and adding 2 variables (ever pregnant and >5-year male-female age gap) enhanced performance (AUC, 0.79; 95% CI, 0.69-0.89). Thirty-five percent had a score of 0, 41% had a score of 1 to 2, and 24% had a score >3. A score >1 resulted in 100% sensitivity, 35.9% specificity, and an IR of 3.25 per 100 PYs. A score >3 resulted in 64.3% sensitivity, 76.8% specificity, and an IR of 5.89 per 100 PYs. CONCLUSIONS: A simple risk assessment tool identified a subset of AGYW in Malawi at high risk for HIV acquisition who may benefit from biomedical HIV prevention.
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Infecções por HIV/prevenção & controle , Infecções por HIV/psicologia , Medição de Risco/métodos , Infecções Sexualmente Transmissíveis/prevenção & controle , Adolescente , Adulto , Preservativos/estatística & dados numéricos , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Humanos , Incidência , Malaui/epidemiologia , Masculino , Estudos Prospectivos , Fatores de Risco , Comportamento Sexual/estatística & dados numéricos , Parceiros Sexuais , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/psicologia , Infecções Sexualmente Transmissíveis/transmissão , Fatores Socioeconômicos , Inquéritos e Questionários , Populações Vulneráveis/psicologia , Adulto JovemRESUMO
OBJECTIVES: Malawi's Option B+ universal antiretroviral therapy (ART) program for pregnant and breastfeeding women does not include routine laboratory monitoring. We report safety outcomes of pregnant women who initiated ART through Option B+. METHODS: We analysed 12-month data from an observational cohort study on Option B+ among women newly initiating tenofovir/lamivudine/efavirenz (TDF/3TC/EFV) at a government antenatal clinic in Lilongwe, Malawi. Proportions of women engaged in care, incidence of DAIDS grade ≥ 2 laboratory toxicity, grade ≥ 3 adverse events (AEs), viral suppression (<1000 copies/mL), birth outcomes and infant HIV infections are reported. RESULTS: At ART initiation, participants (n = 299) had a median age of 26 years (IQR 22-30), median CD4 count of 352 cells/µl (IQR 231-520) and 94% were in WHO Stage 1. We noted 76 incident DAIDS Grade ≥ 2 laboratory results among 58 women, most commonly elevated liver function tests (n = 30 events) and low haemoglobin (n = 27). No women had elevated creatinine. Clinical AEs (n = 45) were predominantly infectious diseases and Grade 3. Five participants (2%) discontinued TDF/3TC/EFV due to virologic failure (3) or toxicity (2). Twelve months after ART initiation, most women were engaged in care (89%) and had HIV RNA < 1000 copies/ml (90%). 8% of pregnancies resulted in preterm birth, 9% were low birthweight (<2500 g), and 2% resulted in infant HIV infection at 6 weeks post-delivery. CONCLUSION: Most women remained on ART and were virally suppressed 12 months after starting Option B+. Few infants contracted HIV perinatally. While some women experienced adverse laboratory events, clinical symptom monitoring is likely reasonable.
OBJECTIFS: Le programme de traitement antirétroviral (ART) universel Option B+ du Malawi pour les femmes enceintes et allaitantes n'inclut pas de suivi de routine en laboratoire. Nous rapportons les résultats en matière de sécurité des femmes enceintes qui ont commencé l'ART via l'Option B+. MÉTHODES: Nous avons analysé les données sur 12 mois d'une étude observationnelle de cohorte portant sur l'Option B+ chez des femmes initiant récemment le traitement par ténofovir/lamivudine/éfavirenz (TDF/3TC/EFV) dans une clinique prénatale du gouvernement à Lilongwe, au Malawi. Les proportions des femmes engagées dans les soins, l'incidence de DAIDS de stade ≥ 2 toxicités de laboratoire, de stade ≥ 3 événements indésirables (EI), la suppression virale (<1000 copies/mL), les résultats de naissance et l'infection infantile par le VIH sont rapportés. RÉSULTATS: A l'initiation de l'ART, les participantes (n = 299) avaient un âge médian de 26 ans (IQR 22-30), taux médian de CD4: 352 cellules/µL (IQR 231-520) et 94% étaient au stade 1 de l'OMS. Nous avons noté 76 incidents DAIDS de stade ≥ 2 résultats de laboratoire chez 58 femmes, le plus souvent, élévationdes tests de la fonction hépatique (n = 30 événements) et faible taux d'hémoglobine (n = 27). Aucune femme n'avait de créatinine élevée. Les EI cliniques (n = 45) étaient principalement des maladies infectieuses et le stade 3. Cinq participantes (2%) ont arrêté TDF/3TC/EFV en raison d'un échec virologique (n=3) ou d'une toxicité (n = 2). Douze mois après l'initiation de l'ART, la plupart des femmes suivaient des soins (89%) et avaient un ARN-VIH <1000 copies/ml (90%). 8% des grossesses ont abouti à une naissance prématurée, 9% avaient un faible poids à la naissance (<2500 g) et 2% ont résulté en une infection par le VIH chez le nourrisson à6 semaines après l'accouchement. CONCLUSION: La plupart des femmes sont restées sous ART et ont connu une suppression virale12 mois après le début de l'Option B+. Peu d'enfants ont contracté le VIH pendant la période périnatale. Bien que certaines femmes aient connu des effets adversesde laboratoire, la surveillance des symptômes cliniques est probablement raisonnable.
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Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Benzoxazinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Tenofovir/uso terapêutico , Adulto , Alcinos , Estudos de Coortes , Ciclopropanos , Quimioterapia Combinada , Feminino , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Malaui , Gravidez , Adulto JovemRESUMO
BACKGROUND: Studies on malignant melanoma have largely focused on Caucasian populations due to higher incidence in lighter-skinned individuals. While there is a well developed body of literature describing melanoma in African-Americans, much less is known about melanoma in black Africans. Prior reports have suggested that it is reportedly extremely rare in black Africans who are considered to mostly have the acral lentiginous subtype. However, an accurate understanding of melanoma in this part of the world is hindered by the very limited nature of prior publications. The aim of this study was to determine the epidemiological profile, anatomical distribution and histopathological features of melanoma presenting in Africans at a tertiary referral hospital in Malawi. METHODS: This is a retrospective study that characterized melanoma cases diagnosed from January 2012 to December 2017, at a cancer referral centre in Malawi. All confirmed, malignant melanoma cases during the study period were retrieved. Data abstracted included age, sex, anatomic site and whether it was a primary or metastatic site. Breslow thickness in millimetres, Clark level of invasion, presence of ulceration and melanoma subtype were also evaluated. RESULTS: One hundred thirty-two cases were included in the study, 81 (61%) were female and 26 (20%) were from a metastatic site. The mean age was 57 years (sd = 15) with the majority in the age group 60-69 years. Males presented at an older age than females. Ninety five percent of cutaneous melanomas were located on acral sites, most commonly the foot (87%) and the most common histopathological subtype was acral lentiginous. Eighty four percent presented with a Breslow thickness over 4 mm (median 9 mm). CONCLUSION: Our study shows that malignant melanoma occurs in black people in Malawi and may be an under-appreciated malignancy. While long term clinical follow-up was not available, most patients presented at late stages of the disease, supporting a poor prognosis. These results suggest that increased awareness of melanoma in black Africans and earlier intervention may have meaningful impacts on outcomes and survival.
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BACKGROUND: Some human immunodeficiency virus (HIV) serodiscordant couples are faced with the dual challenge of preventing HIV transmission to the uninfected partner and avoiding unintended pregnancy. Therefore, we hypothesized that serodiscordance is associated with dual method use at last sex. METHODS: We analyzed data from a cross-sectional survey of HIV-infected men and women attending 2 ante-retroviral therapy clinics in Lilongwe, Malawi. We used Fisher exact test and Wilcoxon rank sum to assess for associations between serodiscordance, covariates, and dual method use. Multivariable logistic regression was used to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CI) of dual method use at last sex, comparing serodiscordant to seroconcordant relationships. Separate analyses were conducted for men and women. RESULTS: We surveyed 253 HIV-infected men, of which 44 (17.4%) were in a known serodiscordant relationship and 63 (24.9%) were using dual methods at last sex. Likewise, among 302 HIV-infected women surveyed, 57 (18.9%) were in a known serodiscordant relationship, and 80 (26.5%) were using dual method at last sex. Serodiscordance was not significantly associated with dual method use at last sex for among HIV-infected men (aOR, 0.62; 95% CI, 0.27-1.44) or women (aOR, 1.21; 95% CI, 0.59-2.47). CONCLUSION: Dual method use was low among all HIV-infected individuals, irrespective of their partner's HIV status. Given these findings, we recommend greater efforts to encourage HIV providers to counsel their patients about the importance of dual method use to prevent both unintended pregnancy and sexually transmitted infections.
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Anticoncepção/estatística & dados numéricos , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , Soropositividade para HIV/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Adulto , Estudos Transversais , Feminino , HIV/imunologia , Humanos , Modelos Logísticos , Malaui/epidemiologia , Masculino , Razão de Chances , Aconselhamento Sexual , Comportamento Sexual , Parceiros Sexuais , Inquéritos e QuestionáriosRESUMO
BACKGROUND: In 2017, Blantyre district had the highest adult HIV prevalence in Malawi (17.7%) and lowest viral suppression (60%). In response, the Ministry of Health expanded prevention and treatment services. We assessed whether outreach to social venues could identify individuals with increased HIV acquisition risk or with unsuppressed HIV not currently reached by clinic-based services. METHODS: We conducted a cross-sectional bio-behavioral survey in Blantyre, Malawi, from January to March 2022. We visited social venues where people meet new sexual partners and government clinics providing HIV testing or STI screening. Participants aged > 15 years were interviewed, and tested for HIV infection if not on ART. HIV recency tests were performed on those testing positive, and dried blood spots (DBS) was collected to quantify viral load and also to identify acute infection in those with HIV- results. RESULTS: HIV prevalence (18.5% vs 8.3%) and unsuppressed HIV infection (3.9% vs 1.7%) were higher among venue-recruited (n=1802) compared with clinic-recruited participants(n=2313). Among PLHIV at both clinics (n=199) and venues (n=289), 79% were virally suppressed. Few had acute(n=1) or recent infection(n=8). Among women, HIV prevalence was four times higher (38.9% venue vs 8.9% clinic). At clinics, PLHIV reporting visiting venues were less likely to be suppressed (54.6 vs 82.6%). More men at venues than at clinics reported paying for sex (49% vs 30%) or having multiple sex partners in the past 4 weeks (32% vs 16%). CONCLUSIONS: Enhanced venue-based prevention and testing for men and women could reduce treatment lapses, HIV treatment outcomes and reduce onward transmission.
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The World Health Organization recommends that all blood donations be screened for transfusion transmissible infections; these data are currently not incorporated into national disease surveillance efforts. We set out to use routinely collected data from blood donors in Blantyre district, Malawi to explore HIV and syphilis prevalence and identify sero-conversions among repeat donors. We conducted a retrospective cohort analysis of blood donation data collected by the Malawi Blood Transfusion Service from 2015 to 2021. All blood donations were routinely screened for HIV and syphilis. We characterized donor demographics as well as screening outcomes, including identifying sero-conversions among repeat donors who previously tested negative on their last donation. A total of 23,280 donations from 5,051 donors were recorded, with a median frequency of donations of 3 (IQR:2-6). Most donors were male (4,294; 85%) and students (3,262; 64.6%). Prevalence of HIV at first donation was 1.0% (52/5,051) and prevalence of syphilis was 1.6% (80/5,051); 52 HIV sero-conversions and 126 syphilis sero-conversions were identified, indicating an incidence rate per 1,000 person-years of 5.9 (95% CI: 4.7, 7.4) and 13.3 (95% CI:11.4, 15.4) respectively. Students had a lower prevalence of HIV and syphilis but higher risk of syphilis seroconversion. While blood donors are generally considered a low-risk population for HIV and syphilis, we were able to identify relatively high rates of undiagnosed HIV and syphilis infections among donors. Routinely collected data from national blood donation services may be used to better understand local HIV and syphilis epidemiology, with the potential to enhance disease surveillance systems. These findings may be used to identify priority prevention areas and populations in Blantyre district that can inform targeted interventions for improved disease prevention, testing and treatment.
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Doadores de Sangue , Infecções por HIV , Sífilis , Humanos , Sífilis/epidemiologia , Malaui/epidemiologia , Doadores de Sangue/estatística & dados numéricos , Masculino , Infecções por HIV/epidemiologia , Feminino , Adulto , Estudos Retrospectivos , Prevalência , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Doação de SangueRESUMO
The most common subtype of lymphoma globally, diffuse large B cell lymphoma (DLBCL), is a leading cause of cancer death in people with HIV. The restructuring of the T cell compartment because of HIV infection and antiretroviral therapy (ART) may have implications for modern treatment selection, but current understanding of these dynamic interactions is limited. Here, we investigated the T cell response to DLBCL by sequencing the T cell receptor (TCR) repertoire in a cohort of HIV-negative (HIV-), HIV+/ART-experienced, and HIV+/ART-naive patients with DLBCL. HIV+/ART-naive tumor TCR repertoires were more clonal and more distinct from each other than HIV- and HIV+/ART-experienced ones. Further, increased overlap between tumor and blood TCR repertoires was associated with improved survival and HIV/ART status. Our study describes TCR repertoire characteristics for the first time to our knowledge in an African DLBCL cohort and demonstrates contributions of HIV infection and ART exposure to the DLBCL TCR repertoire.
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Infecções por HIV , Linfoma Difuso de Grandes Células B , Receptores de Antígenos de Linfócitos T , Humanos , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/virologia , Infecções por HIV/imunologia , Infecções por HIV/tratamento farmacológico , Masculino , Receptores de Antígenos de Linfócitos T/metabolismo , Feminino , Pessoa de Meia-Idade , Adulto , Linfócitos T/imunologia , Antirretrovirais/uso terapêuticoRESUMO
The pathology laboratory at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi was established in 2011. We published our initial experiences in laboratory development and telepathology in 2013 and 2016, respectively. The purpose of this paper is to provide an update on our work by highlighting the positive role laboratory development has played in improving regional cancer care and research. In addition, we provide a summary of the adult pathology data from specimens received between July 1, 2011, and May 31, 2019, with an emphasis on malignant diagnoses. We compare these summaries to estimates of cancer incidence in this region to identify gaps and future needs.
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Introduction: In East and Southern Africa, people with HIV (PWH) experience worse cancer-related outcomes and are at higher risk of developing certain cancers. Siloed care delivery pathways pose a substantial barrier to co-management of HIV and cancer care delivery. Methods: We conducted cross-sectional studies of adult cancer patients at public radiotherapy and oncology units in Malawi (Kamuzu Central Hospital), Zimbabwe (Parirenyatwa Group of Hospitals), and South Africa (Charlotte Maxeke Hospital) between 2018-2019. We abstracted cancer- and HIV-related data from new cancer patient records and used Poisson regression with robust variance to identify patient characteristics associated with HIV documentation. Results: We included 1,648 records from Malawi (median age 46 years), 1,044 records from South Africa (median age 55 years), and 1,135 records from Zimbabwe (median age 52 years). Records from all three sites were predominately from female patients; the most common cancers were cervical (Malawi [29%] and Zimbabwe [43%]) and breast (South Africa [87%]). HIV status was documented in 22% of cancer records from Malawi, 92% from South Africa, and 86% from Zimbabwe. Patients with infection-related cancers were more likely to have HIV status documented in Malawi (adjusted prevalence ratio [aPR]: 1.92, 95% confidence interval [CI]: 1.56-2.38) and Zimbabwe (aPR: 1.16, 95%CI: 1.10-1.22). Patients aged ≥60 years were less likely to have HIV status documented (Malawi: aPR: 0.66, 95% CI: 0.50-0.87; Zimbabwe: aPR: 0.76, 95%CI: 0.72-0.81) than patients under age 40 years. Patient age and cancer type were not associated with HIV status documentation in South Africa. Conclusion: Different cancer centers have different gaps in HIV status documentation and will require tailored strategies to improve processes for ascertaining and recording HIV-related information in cancer records. Further research by our consortium to identify opportunities for integrating HIV and cancer care delivery is underway.
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INTRODUCTION: In East and Southern Africa, people with HIV (PWH) experience worse cancer-related outcomes and are at higher risk of developing certain cancers. Siloed care delivery pathways pose a substantial barrier to co-management of HIV and cancer care delivery. METHODS: We conducted cross-sectional studies of adult cancer patients at public radiotherapy and oncology units in Malawi (Kamuzu Central Hospital), Zimbabwe (Parirenyatwa Group of Hospitals), and South Africa (Charlotte Maxeke Hospital) between 2018 and 2019. We abstracted cancer- and HIV-related data from new cancer patient records and used Poisson regression with robust variance to identify patient characteristics associated with HIV documentation. RESULTS: We included 1,648 records from Malawi (median age 46 years), 1,044 records from South Africa (median age 55 years), and 1,135 records from Zimbabwe (median age 52 years). Records from all three sites were predominately from female patients; the most common cancers were cervical (Malawi [29%] and Zimbabwe [43%]) and breast (South Africa [87%]). HIV status was documented in 22% of cancer records from Malawi, 92% from South Africa, and 86% from Zimbabwe. Patients with infection-related cancers were more likely to have HIV status documented in Malawi (adjusted prevalence ratio [aPR]: 1.92, 95% confidence interval [CI]: 1.56-2.38) and Zimbabwe (aPR: 1.16, 95%CI: 1.10-1.22). Patients aged ≥ 60 years were less likely to have HIV status documented (Malawi: aPR: 0.66, 95% CI: 0.50-0.87; Zimbabwe: aPR: 0.76, 95%CI: 0.72-0.81) than patients under age 40 years. Patient age and cancer type were not associated with HIV status documentation in South Africa. CONCLUSION: Different cancer centers have different gaps in HIV status documentation and will require tailored strategies to improve processes for ascertaining and recording HIV-related information in cancer records. Further research by our consortium to identify opportunities for integrating HIV and cancer care delivery is underway.