Virologic outcomes with tenofovir-lamivudine-dolutegravir in adults failing PI-based second-line ART.

Background: In South African antiretroviral guidelines, selected patients failing second-line protease inhibitor (PI)-based therapy qualify for genotypic resistance testing - those with PI resistance receive darunavir-based third-line regimens; those without PI resistance continue current regimen with adherence support. The Western Cape province, from September 2020, implemented a strategy of tenofovir-lamivudine-dolutegravir (TLD) for patients, provided there was no tenofovir resistance, irrespective of PI resistance. Objectives: To evaluate virologic outcomes with TLD among adults failing second-line PI regimens with no tenofovir resistance. Method: An observational cohort study comparing outcomes in patients switched to TLD with those continuing the same PI or switched to darunavir-based regimens. Follow-up was until virologic suppression (HIV-1 RNA < 400 copies/mL), or at the point of censoring. Results: One hundred and thirty-three patients switched to TLD, 101 to darunavir-based regimens, and 121 continued with the same PI. By 12 months, among patients with PI resistance, 42/47 (89%) in the TLD group had HIV-1 RNA < 400 copies/mL compared to 91/99 (92%) in the darunavir group (hazard ratio, 1.11; 95% confidence interval, 0.77-1.60). In patients without PI resistance, 66/86 (77%) in the TLD group had HIV-1 RNA < 400 copies/mL compared to 42/120 (35%) in those continuing with the same PI (hazard ratio, 4.03; 95% confidence interval, 2.71-5.98). Two patients receiving TLD developed virologic failure with high-level dolutegravir resistance. Conclusion: Amongst patients failing second-line PI with no PI resistance, switching to TLD was associated with higher virologic suppression, likely due to improved adherence. Virologic outcomes were similar in patients with PI resistance switched to darunavir-based regimens or TLD.

Prevalence and clinical spectrum of hypertensive retinopathy among hypertension clinic patients at Queen Elizabeth Central Hospital in Malawi.

Background: Prevalence and spectrum of hypertensive retinopathy in the population reflects the status of hypertension control and the associated risks for cardiovascular events. We investigated the prevalence and clinical spectrum of hypertensive retinopathy among patients attending hypertension clinic at a tertiary hospital in Malawi. Methods: This was a cross-sectional study of systematically selected patients attending hypertension clinic at Queen Elizabeth Central Hospital. Patient interviews using a structured questionnaire and review of patients' medical records (health passports) were done to obtain the following information: demographics, duration since the diagnosis of hypertension, history of stroke and blood pressure measurements. The presence and severity of hypertensive retinopathy was determined by dilated fundoscopy through slit lamp biomicroscopy. Results: We recruited 104 patients. Women outnumbered men by 3:1. Women tended to be younger compared to men (mean ages 54 and 61 years respectively). Of the surveyed patients, 80% had sub-optimal blood pressure control and 75% had evidence of hypertensive retinopathy. History of stroke was associated with hypertensive retinopathy. Conclusions: Hypertensive retinopathy is very common in patients attending the hypertension clinic at Queen Elizabeth Central Hospital in Blantyre, Malawi. This may be a reflection of sub-optimal blood pressure control in this patient population. There is a need to identify the actual reasons, rectify them and intensify intervention in control of hypertension in this patient population.

Improving hospital-based trauma care for road traffic injuries in Malawi.

BACKGROUND: The mortality rate from road traffic injuries has increased in sub-Saharan Africa as the number of motor vehicles increase. This study examined the capacity of hospitals along Malawi's main north-south highway to provide emergency trauma care. METHODS: Structured interviews and checklists were used to evaluate the infrastructure, personnel, supplies, and equipment at all four of Malawi's central hospitals, ten district hospitals, and one mission hospital in 2014. Most of these facilities are along the main north-south highway that spans the country. RESULTS: Between July 2013 and March 2014, more than 9 200 road traffic injuries (RTIs) and 100 RTI deaths were recorded by the participating hospitals. All of the hospitals reported staff shortages, especially during nights and weekends. Few clinicians had completed formal training in emergency trauma management, and healthcare workers reported gaps in knowledge and skills, especially at district hospitals. Most central hospitals had access to the critical supplies and medications necessary for trauma care, but district hospitals lacked some of the supplies and equipment needed for diagnosis, treatment, and personal protection. CONCLUSION: The mortality and disability burden from road traffic injuries in Malawi (and other low-income countries in sub-Saharan Africa) can be reduced by ensuring that every central and district hospital has a dedicated trauma unit with qualified staff who have completed primary trauma care courses and have access to the equipment necessary to save lives.

The Treatment of Possible Severe Infection in Infants: An Open Randomized Safety Trial of Parenteral Benzylpenicillin and Gentamicin Versus Ceftriaxone in Infants <60 days of Age in Malawi.

BACKGROUND: The World Health Organization recommends benzylpenicillin and gentamicin as antimicrobial treatment for infants with sepsis in low-income settings, and ceftriaxone or cefotaxime as an alternative. In a meta-analysis from 13 low-income settings, Staphylococcus aureus, Klebsiella spp. and Escherichia coli accounted for 55% of infants with sepsis. In a review of bacterial meningitis, resistance to third generation cephalosporins was >50% of all isolates, and 44% of Gram-negative isolates were gentamicin resistant. However, ceftriaxone may cause neonatal jaundice, and gentamicin may cause deafness. Therefore, we compared parenteral benzylpenicillin plus gentamicin with ceftriaxone as first-line treatment, assessing outcome and adverse events. METHODS: This was an open randomized trial carried out in the Queen Elizabeth Central Hospital, Blantyre, Malawi, from 2010 to 2013. Infants <60 days of age with possible severe sepsis received either benzylpenicillin and gentamicin or ceftriaxone. Adverse events and outcomes were recorded until 6 months post discharge. RESULTS: Three-hundred forty-eight infants were included in analyses. Outcome in the benzylpenicillin and gentamicin and ceftriaxone groups was similar; deaths were 13.7% and 16.5% and sequelae were 14.5% and 11.2%, respectively. More infants in the penicillin/gentamicin group required phototherapy: 15% versus 5%, P = 0.03. Thirteen (6%) survivors had bilateral hearing loss. There was no difference between the treatment groups. By 6 months post discharge, 11 more infants had died, and 17 more children were found to have sequelae. CONCLUSIONS: Ceftriaxone and gentamicin are safe for infants in our setting. Infants should receive long-term follow-up as many poor outcomes occurred after hospital discharge.

First Responders and Prehospital Care for Road Traffic Injuries in Malawi.

Introduction Road traffic collisions are a common cause of injuries and injury-related deaths in sub-Saharan Africa (SSA). Basic prehospital care can be the difference between life and death for injured drivers, passengers, and pedestrians. Problem This study examined the challenges associated with current first response practices in Malawi. METHODS: In April 2014, focus groups were conducted in two areas of Malawi: Karonga (in the Northern Region) and Blantyre (in the Southern Region; both are along the M1 highway), and a qualitative synthesis approach was used to identify themes. All governmental and nongovernmental first response organizations identified by key informants were contacted, and a checklist was used to identify the services they offer. RESULTS: Access to professional prehospital care in Malawi is almost nonexistent, aside from a few city fire departments and private ambulance services. Rapid transportation to a hospital is usually the primary goal of roadside care because of limited first aid knowledge and a lack of access to basic safety equipment. The key informants recommended: expanding community-based first aid training; emphasizing umunthu (shared humanity) to inspire bystander involvement in roadside care; empowering local leaders to coordinate on-site responses; improving emergency communication systems; equipping traffic police with road safety gear; and expanding access to ambulance services. CONCLUSION: Prehospital care in Malawi would be improved by the creation of a formal network of community leaders, police, commercial drivers, and other lay volunteers who are trained in basic first aid and are equipped to respond to crash sites to provide roadside care to trauma patients and prepare them for safe transport to hospitals. Chokotho L , Mulwafu W , Singini I , Njalale Y , Maliwichi-Senganimalunje L , Jacobsen KH . First responders and prehospital care for road traffic injuries in Malawi. Prehosp Disaster Med. 2017;32(1):14-19.

Predictors of late virologic failure after initial successful suppression of HIV replication on efavirenz-based antiretroviral therapy.

BACKGROUND: Practical issues, including cost, hinder implementing virologic monitoring of patients on antiretroviral therapy (ART) in resource-limited settings. We evaluated factors that might guide monitoring frequency and efforts to prevent treatment failure after initial virologic suppression. METHODS: Participants were the 911 HIV-infected antiretroviral-naïve adults with CD4 count <300 cells/µL who started efavirenz-based ART in the international A5175/PEARLS trial and achieved HIV-1 RNA <1000 copies/mL at 24 weeks. Participant report of ART adherence was evaluated using a structured questionnaire in monthly interviews. Adherence and readily available clinical and laboratory measures were evaluated as predictors of late virologic failure (late VF: confirmed HIV-1 RNA ≥1000 copies/mL after 24 weeks). RESULTS: During median follow-up of 3.5 years, 82/911 participants (9%) experienced late VF. Of 516 participants reporting missed doses during the first 24 weeks of ART, 55 (11%) experienced late VF, compared with 27 (7%) of 395 participants reporting no missed doses (hazard ratio: 1.73; 95% CI: 1.08, 2.73). This difference persisted in multivariable analysis, in which lower pre-ART hemoglobin and absence of Grade ≥3 laboratory results prior to week 24 were also associated with higher risk of late VF. DISCUSSION: In this clinical trial, the late VF rate after successful suppression was very low. If achievable in routine clinical practice, virologic monitoring involving infrequent (e.g. annual) measurements might be considered; the implications of this for development of resistance need evaluating. Patients reporting missed doses early after ART initiation, despite achieving initial suppression, might require more frequent measurement and/or strategies for promoting adherence.

Knowledge and perception about tuberculosis among children attending primary school in Ntcheu District, Malawi.

BACKGROUND: Knowledge and perceptions about tuberculosis (TB) can influence care-seeking behavior and adherence to treatment. Previous studies in Malawi were conducted to assess knowledge and attitudes regarding TB in adults, with limited data on knowledge in children. OBJECTIVES: This study assessed knowledge and perceptions about TB in children aged 10-14 years attending primary school in Ntcheu District, Malawi. DESIGN: A cross-sectional study was conducted in four primary schools in Ntcheu District. Data on knowledge and perception of TB were collected using a structured questionnaire. Pearson chi-square test was used to determine the association between socioeconomic factors and TB knowledge and perception. A P<0.05 was considered significant. RESULTS: The study found that the learners had high knowledge regarding the cause, spread, and TB preventive measures. Almost 90% of learners knew that TB is caused by a germ, however, a lower proportion knew about TB symptoms ie, night sweats (49%) and enlarged cervical lymph nodes (40%). We found that 68% of learners did not know the duration of anti-TB treatment. No association was found between age, learners' grade, and knowledge (P>0.05). CONCLUSION: Lack of knowledge regarding TB and gaps identified, may be due to a deficiency in the content of the school curriculum or the availability of information, education, and communication materials. This is the first study to report on knowledge and perceptions of TB among primary school learners in Malawi. These results will inform the development of relevant information, education, and communication materials to enhance awareness about TB among school going children.

Factors Influencing Delayed Health Care Seeking Among Pulmonary Tuberculosis Suspects in Rural Communities in Ntcheu District, Malawi.

Delayed diagnosis and treatment of tuberculosis (TB) among individuals suspected of having TB may lead to continued transmission of Mycobacterium tuberculosis in communities, higher mortality rates, and increase in government health expenditure because of prolonged illness due to late diagnosis and treatment initiation. The study explored factors leading to delayed health care seeking among individuals living in Ntcheu District, Malawi. Two key informant interviews, 16 in-depth interviews, and three focus group discussions were conducted. Participants were aged 18 years and older and never had TB. Data were analyzed using content analysis and factors were identified: inadequate knowledge about cause and transmission of TB, low self-awareness of personal risk to TB, cultural and traditional beliefs about sources of TB, stigma, and strong belief in witchcraft as a cause of illness. The TB Control Program needs to invest in social mobilization and education of communities to mitigate early health care seeking.

A Randomized Comparison of Anthropomorphic Changes With Preferred and Alternative Efavirenz-Based Antiretroviral Regimens in Diverse Multinational Settings.

Background. Existing data on anthropomorphic changes in resource-limited settings primarily come from observational or cross-sectional studies. Data from randomized clinical trials are needed to inform treatment decisions in these areas of the world. Methods. The AIDS Clinical Trials Group Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) study was a prospective, randomized evaluation of the efficacy of emtricitabine/tenofovir + efavirenz (FTC/TDF + EFV) vs lamivudine/zidovudine + efavirenz (3TC/ZDV + EFV) for the initial treatment of human immunodeficiency virus (HIV)-1-infected individuals from resource-diverse settings. Changes in anthropomorphic measures were analyzed using mixed-effect models for repeated measurements, using all available measurements at weeks 48, 96, and 144. Intent-to-treat results are presented; as-treated results were similar. Results. Five hundred twenty-six participants were randomized to FTC/TDF + EFV, and 519 participants were randomized to 3TC/ZDV + EFV. Significantly greater increases from baseline to week 144 were seen among those randomized to FTC/TDF + EFV vs 3TC/ZDV + EFV in all measures except waist-to-hip ratio, with the following mean changes: weight, 4.8 vs 3.0 kg; body mass index, 1.8 vs 1.1 kg/m(2); mid-arm, 1.7 vs 0.7 cm; waist, 5.2 vs 4.3 cm; hip, 3.8 vs 1.4 cm; and mid-thigh circumference, 3.1 vs 0.9 cm. There were 7 clinical diagnoses of lipoatrophy in the 3TC/ZDV + EFV arm compared with none in the FTC/TDF + EFV arm. The proportion of overweight or obese participants increased from 25% (week 0) to 42% (week 144) for FTC/TDF + EFV and from 26% to 38% for 3TC/ZDV + EFV. Conclusions. Our findings support first-line use of FTC/TDF + EFV in resource-limited settings and emphasize the need for interventions to limit weight gain among overweight or obese HIV-infected participants in all settings.

The association between multiple sources of information and risk perceptions of tuberculosis, Ntcheu district, Malawi.

BACKGROUND: Tuberculosis (TB) is one of the main causes of death in developing countries. Awareness and perception of risk of TB could influence early detection, diagnosis and care seeking at treatment centers. However, perceptions about TB are influenced by sources of information. AIM: This study aimed to determine the association between multiple sources of information, and perceptions of risk of TB among adults aged 18-49 years. METHODS: A cross-sectional study was conducted in Ntcheu district in Malawi. A total of 121 adults were sampled in a three-stage simple random sampling technique. Data were collected using a structured questionnaire. Perceptions of risk were measured using specific statements that reflected common myths and misconceptions. Low risk perception implied a person having strong belief in myths and misconceptions about TB and high risk perception meant a person having no belief in myths or misconceptions and demonstrated understanding of the disease. RESULTS: Females were more likely to have low risk perceptions about TB compared to males (67.7% vs. 32.5%, p = 0.01). The higher the household asset index the more likely an individual had higher risk perceptions about TB (p = 0.006). The perception of risk of TB was associated with sources of information (p = 0.03). Use of both interpersonal communication and mass media was 2.8 times more likely to be associated with increased perception of risk of TB (Odds Ratio [OR] = 2.8; 95% Confidence interva1[CI]: 3.1-15. 6; p = 0.01). After adjusting for sex and asset ownership, use of interpersonal communication and mass media were more likely to be associated with higher perception of risk of TB (OR, 2.0; 95% CI: 1.65-10.72; p = 0.003) compared with interpersonal communication only (OR 1.6, 95%; CI: 1.13-8.98, p = 0.027). CONCLUSION: The study found that there was association between multiple sources of information, and higher perceptions of risk of TB among adults aged 18-49 years.