Prevalence and antimicrobial resistance profiles of respiratory microbial flora in African children with HIV-associated chronic lung disease

Abstract Background HIV-associated chronic lung disease (CLD) is common among children living with HIV (CLWH) in sub-Saharan Africa, including those on antiretroviral therapy (ART). However, the pathogenesis of CLD and its possible association with microbial determinants remain poorly understood. We investigated the prevalence, and antibiotic susceptibility of Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), and Moraxella catarrhalis (MC) among CLWH (established on ART) who had CLD (CLD+), or not (CLD-) in Zimbabwe and Malawi. Methods Nasopharyngeal swabs (NP) and sputa were collected from CLD+ CLWH (defined as forced-expiratory volume per second z-score < − 1 without reversibility post-bronchodilation with salbutamol), at enrolment as part of a randomised, placebo-controlled trial of azithromycin (BREATHE trial - NCT02426112), and from age- and sex-matched CLD- CLWH. Samples were cultured, and antibiotic susceptibility testing was conducted using disk diffusion. Risk factors for bacterial carriage were identified using questionnaires and analysed using multivariate logistic regression. Results A total of 410 participants (336 CLD+, 74 CLD-) were enrolled (median age, 15 years [IQR = 13–18]). SP and MC carriage in NP were higher in CLD+ than in CLD- children: 46% (154/336) vs. 26% (19/74), p = 0.008; and 14% (49/336) vs. 3% (2/74), p = 0.012, respectively. SP isolates from the NP of CLD+ children were more likely to be non-susceptible to penicillin than those from CLD- children (36% [53/144] vs 11% [2/18], p = 0.036). Methicillin-resistant SA was uncommon [4% (7/195)]. In multivariate analysis, key factors associated with NP bacterial carriage included having CLD (SP: adjusted odds ratio (aOR) 2 [95% CI 1.1–3.9]), younger age (SP: aOR 3.2 [1.8–5.8]), viral load suppression (SP: aOR 0.6 [0.4–1.0], SA: 0.5 [0.3–0.9]), stunting (SP: aOR 1.6 [1.1–2.6]) and male sex (SA: aOR 1.7 [1.0–2.9]). Sputum bacterial carriage was similar in both groups (50%) and was associated with Zimbabwean site (SP: aOR 3.1 [1.4–7.3], SA: 2.1 [1.1–4.2]), being on ART for a longer period (SP: aOR 0.3 [0.1–0.8]), and hot compared to rainy season (SP: aOR 2.3 [1.2–4.4]). Conclusions CLD+ CLWH were more likely to be colonised by MC and SP, including penicillin-non-susceptible SP strains, than CLD- CLWH. The role of these bacteria in CLD pathogenesis, including the risk of acute exacerbations, should be further studied.

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Distinct lung microbiota associate with HIV-associated chronic lung disease in children

Scientific Reports ◽

10.1038/s41598-020-73085-1 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Sudha Bhadriraju ◽

Douglas W. Fadrosh ◽

Meera K. Shenoy ◽

Din L. Lin ◽

Kole V. Lynch ◽

...

Keyword(s):

Lung Disease ◽

Chronic Lung Disease ◽

Cross Sectional Study ◽

Sub Saharan Africa ◽

Hiv Positive ◽

Cross Sectional ◽

Pathogenic Potential ◽

Co Morbidity ◽

Sub Saharan

Abstract Chronic lung disease (CLD) is a common co-morbidity for HIV-positive children and adolescents on antiretroviral therapy (ART) in sub-Saharan Africa. In this population, distinct airway microbiota may differentially confer risk of CLD. In a cross-sectional study of 202 HIV-infected children aged 6–16 years in Harare, Zimbabwe, we determined the association of sputum microbiota composition (using 16S ribosomal RNA V4 gene region sequencing) with CLD defined using clinical, spirometric, or radiographic criteria. Forty-two percent of children were determined to have CLD according to our definition. Dirichlet multinomial mixtures identified four compositionally distinct sputum microbiota structures. Patients whose sputum microbiota was dominated by Haemophilus, Moraxella or Neisseria (HMN) were at 1.5 times higher risk of CLD than those with Streptococcus or Prevotella (SP)-dominated microbiota (RR = 1.48, p = 0.035). Cell-free products of HMN sputum microbiota induced features of epithelial disruption and inflammatory gene expression in vitro, indicating enhanced pathogenic potential of these CLD-associated microbiota. Thus, HIV-positive children harbor distinct sputum microbiota, with those dominated by Haemophilus, Moraxella or Neisseria associated with enhanced pathogenesis in vitro and clinical CLD.

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Vitamin D3 and calcium carbonate supplementation for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology (VITALITY Trial): study protocol for a randomised placebo-controlled trial

10.21203/rs.3.rs-624718/v1 ◽

2021 ◽

Author(s):

Nyasha Veronica Dzavakwa ◽

Molly Chisenga ◽

Grace McHugh ◽

Suzanne Filteau ◽

Celia Louise Gregson ◽

...

Keyword(s):

Vitamin D ◽

Calcium Carbonate ◽

Bone Mineral ◽

Bone Health ◽

Controlled Trial ◽

Sub Saharan Africa ◽

Z Score ◽

Sub Saharan ◽

Vitamin D 3 ◽

Living With Hiv

Abstract Background: Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D 3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV. Methods/design: We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D 3 (20000iu) plus daily calcium carbonate (500mg) supplementation for 48 weeks. 840 children living with HIV aged 11-19 years taking ART for ≥6 months will be enrolled and followed up for 96 weeks. The primary outcome is total body less-head bone mineral content for lean mass adjusted for height (TBLH-BMC LBM ) Z-score at 48 weeks, measured by dual-energy x-ray absorptiometry (DEXA). Secondary outcomes are DEXA-measured Lumbar Spine Bone Mineral Apparent Density Z-score, number of respiratory infections, lean muscle mass and grip-strength at 48 and 96 weeks, and TBLH-BMC LBM Z-scores at 96 weeks. Sub studies will investigate the effect of the intervention on vitamin D 3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function. Discussion: This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual through childhood is critical for optimising adolescent and early adult bone health, and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings.Trial registration: Pan African Clinical Trials Registry ID: PACTR20200989766029. Date ofregistration: 3 September 2020. URL of trial registry record: https://pactr.samrc.ac.za

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Cytomegalovirus-Specific Immunoglobulin G is associated with chronic lung disease in children and adolescents from sub-Saharan Africa with perinatal HIV infection

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1757 ◽

2020 ◽

Author(s):

Dan Hameiri Bowen ◽

Evgeniya Sovershaeva ◽

Bethany Charlton ◽

Cecilie Schive ◽

Jon Odland ◽

...

Keyword(s):

Lung Disease ◽

Children And Adolescents ◽

Chronic Lung Disease ◽

Immunoglobulin G ◽

Cross Sectional Study ◽

Sub Saharan Africa ◽

Cross Sectional ◽

Perinatal Hiv ◽

Specific Immunoglobulin ◽

Sub Saharan

Abstract In a cross-sectional study of 296 perinatally HIV-infected children and adolescents from Zimbabwe, individuals with the top tertile of CMV-Specific Immunoglobulin G titre had an increased odds of chronic lung disease (odds ratio 3.33; 95% confidence interval 1.37-8.85; p = 0.010).

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Coping With HIV/AIDS in Sub-Saharan Africa: What Hinders People Living With HIV/AIDS (PLWHA) From Seeking Care in Health Care Institutions?

PsycEXTRA Dataset ◽

10.1037/e513522013-001 ◽

2011 ◽

Keyword(s):

Health Care ◽

Sub Saharan Africa ◽

People Living With Hiv ◽

Health Care Institutions ◽

Sub Saharan ◽

Living With Hiv ◽

Hiv Aids

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Relationships with caregivers and mental health outcomes among adolescents living with HIV: a prospective cohort study in South Africa

BMC Public Health ◽

10.1186/s12889-020-10147-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yulia Shenderovich ◽

Mark Boyes ◽

Michelle Degli Esposti ◽

Marisa Casale ◽

Elona Toska ◽

...

Keyword(s):

Mental Health ◽

South Africa ◽

Cohort Study ◽

Mental Health Problems ◽

Health Problems ◽

Sub Saharan Africa ◽

Depression Symptoms ◽

Sub Saharan ◽

Positive Caregiving ◽

Living With Hiv

Abstract Background Mental health problems may impact adherence to anti-retroviral treatment, retention in care, and consequently the survival of adolescents living with HIV. The adolescent-caregiver relationship is an important potential source of resilience. However, there is a lack of longitudinal research in sub-Saharan Africa on which aspects of adolescent-caregiver relationships can promote mental health among adolescents living with HIV. We draw on a prospective longitudinal cohort study undertaken in South Africa to address this question. Methods The study traced adolescents aged 10–19 initiated on antiretroviral treatment in government health facilities (n = 53) within a health district of the Eastern Cape province. The adolescents completed standardised questionnaires during three data collection waves between 2014 and 2018. We used within-between multilevel regressions to examine the links between three aspects of adolescent-caregiver relationships (caregiver supervision, positive caregiving, and adolescent-caregiver communication) and adolescent mental health (depression symptoms and anxiety symptoms), controlling for potential confounders (age, sex, rural/urban residence, mode of infection, household resources), n=926 adolescents. Results Improvements in caregiver supervision were associated with reductions in anxiety (0.98, 95% CI 0.97–0.99, p=0.0002) but not depression symptoms (0.99, 95% CI 0.98–1.00, p=.151), while changes in positive caregiving were not associated with changes in mental health symptoms reported by adolescents. Improvements in adolescent-caregiver communication over time were associated with reductions in both depression (IRR=0.94, 95% CI 0.92–0.97, p<.0001) and anxiety (0.91, 95% CI 0.89–0.94, p<.0001) symptoms reported by adolescents. Conclusions Findings highlight open and supportive adolescent-caregiver communication and good caregiver supervision as potential factors for guarding against mental health problems among adolescents living with HIV in South Africa. Several evidence-informed parenting programmes aim to improve adolescent-caregiver communication and caregiver supervision, and their effect on depression and anxiety among adolescents living with HIV should be rigorously tested in sub-Saharan Africa. How to improve communication in other settings, such as schools and clinics, and provide communication support for caregivers, adolescents, and service providers through these existing services should also be considered.

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Interventions to Improve Adherence to Antiretroviral Therapy (ART) in Sub-Saharan Africa: An Updated Systematic Review

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18052477 ◽

2021 ◽

Vol 18 (5) ◽

pp. 2477

Author(s):

Panmial Priscilla Damulak ◽

Suriani Ismail ◽

Rosliza Abdul Manaf ◽

Salmiah Mohd Said ◽

Oche Agbaji

Keyword(s):

Systematic Review ◽

Antiretroviral Therapy ◽

Behavioral Interventions ◽

Controlled Trial ◽

Self Report ◽

Sub Saharan Africa ◽

Art Adherence ◽

Study Characteristics ◽

Combination Study ◽

Sub Saharan

Optimal adherence to antiretroviral therapy (ART) remains the bedrock of effective therapy and management of human immunodeficiency virus (HIV). This systematic review examines the effect of interventions in improving ART adherence in sub-Saharan Africa (SSA), which bears the largest global burden of HIV infection. In accordance with PRISMA guidelines, and based on our inclusion and exclusion criteria, PUBMED, MEDLINE, and Google Scholar databases were searched for published studies on ART adherence interventions from 2010 to 2019. Thirty-one eligible studies published between 2010 to 2019 were identified, the categories of interventions were structural, behavioral, biological, cognitive, and combination. Study characteristics varied across design, intervention type, intervention setting, country, and outcome measurements. Many of the studies were behavioral interventions conducted in hospitals with more studies being randomized controlled trial (RCT) interventions. Despite the study variations, twenty-four studies recorded improvements. Notwithstanding, more quality studies such as RCTs should be conducted, especially among key affected populations (KAPs) to control transmission of resistant strains of the virus. Reliable objective measures of adherence should replace the conventional subjective self-report. Furthermore, long-term interventions with longer duration should be considered when evaluating the effectiveness of interventions.

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Addressing Pediatric HIV Pretreatment Drug Resistance and Virologic Failure in Sub-Saharan Africa: A Cost-Effectiveness Analysis of Diagnostic-Based Strategies in Children ≥3 Years Old

Diagnostics ◽

10.3390/diagnostics11030567 ◽

2021 ◽

Vol 11 (3) ◽

pp. 567

Author(s):

Mutita Siriruchatanon ◽

Shan Liu ◽

James G. Carlucci ◽

Eva A. Enns ◽

Horacio A. Duarte

Keyword(s):

Drug Resistance ◽

Cost Effectiveness ◽

Virologic Failure ◽

Pediatric Hiv ◽

Sub Saharan Africa ◽

Financial Investment ◽

Switching Strategy ◽

Wide Range ◽

Sub Saharan ◽

Living With Hiv

Improvement of antiretroviral therapy (ART) regimen switching practices and implementation of pretreatment drug resistance (PDR) testing are two potential approaches to improve health outcomes for children living with HIV. We developed a microsimulation model of disease progression and treatment focused on children with perinatally acquired HIV in sub-Saharan Africa who initiate ART at 3 years of age. We evaluated the cost-effectiveness of diagnostic-based strategies (improved switching and PDR testing), over a 10-year time horizon, in settings without and with pediatric dolutegravir (DTG) availability as first-line ART. The improved switching strategy increases the probability of switching to second-line ART when virologic failure is diagnosed through viral load testing. The PDR testing strategy involves a one-time PDR test prior to ART initiation to guide choice of initial regimen. When DTG is not available, PDR testing is dominated by the improved switching strategy, which has an incremental cost-effectiveness ratio (ICER) of USD 579/life-year gained (LY), relative to the status quo. If DTG is available, improved switching has a similar ICER (USD 591/LY) relative to the DTGstatus quo. Even when substantial financial investment is needed to achieve improved regimen switching practices, the improved switching strategy still has the potential to be cost-effective in a wide range of sub-Saharan African countries. Our analysis highlights the importance of strengthening existing laboratory monitoring systems to improve the health of children living with HIV.

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