Development of nevirapine resistance in children exposed to the prevention of mother-to-child HIV-1 transmission programme in Maputo, Mozambique

Background: Single-dose nevirapine (sd-NVP) has been the main option for prevention of mother-to-child transmission (PMTCT) of HIV-1 in low-resource settings. However, sd-NVP can induce the selection of HIV-1 resistant mutations in mothers and infants. In Mozambique, there are limited data regarding the profile of NVP resistance associated mutations (RAM) in the context of PMTCT. Objectives: To assess the prevalence and the factors associated with NVP RAM among children born to HIV-1 infected mothers enrolled in the PMTCT programme adopted in Mozambique. Methods: One hundred and fifty seven children aged 6 to 48 weeks were sequentially included (July 2011 to March 2012) at four centres in Maputo. Genotyping of RAM was performed in samples with HIV-1 RNA≥ 100 copies/μL (Viroseq). Sequencing was performed with ABI 3100 (Applied Biosystems). Logistic regression modelling was undertaken to identify the factors associated with NVP RAM. Results: Seventy-nine children had their samples genotyped. Their median age was 7.0 (3–12) months and 92.4% received prophylaxis with sd-NVP at birth plus daily NVP. 35.4% of mothers received antiretrovirals (ARVs) for PMTCT. ARV RAM were detected in 43 (54.4%) of the children. 45.6% of these children had at least one NVP RAM. The most common mutations associated with NVP resistance were K103N (n = 16) and Y181C (n = 15). NVP RAM was significantly associated with mother exposure to PMTCT (crude odds ratio [OR] 30.3, 95% CI 4.93–186.34) and with mother’s CD4 count < 350 cells/mm3 (crude OR 3.08, 95% CI 1.02–9.32). In the multivariable analysis the mother’s exposure to PMTCT was the only variable significantly associated with NVP RAM (adjusted OR 48.65, 95% CI 9.33–253.66). Conclusions: We found a high prevalence of NVP RAM among children who were exposed to the drug regimen for PMTCT in Mozambique. The mothers’ exposure to PMTCT significantly increased the risk of NVP RAM.This study was funded by the Associação para a Investigação e Desenvolvimento da Faculdade de Medicina (AIDFM). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Usability of simplified audiometry and electrocardiogram during treatment of drug-resistant tuberculosis in Mozambique: a qualitative study

Abstract Background In 2021, there were approximately 450,000 cases of drug-resistant tuberculosis (DR-TB) worldwide. The treatment of DR-TB historically included expensive and toxic injectable drugs leading to adverse effects including ototoxicity and Electrocardiogram (ECG) abnormalities. This study described the perspectives of healthcare providers and people with DR-TB on the usability of simplified audiometry and ECG for monitoring treatment adverse effects. Methods A qualitative study was conducted in December 2019 across four provinces in Mozambique, namely Maputo, Gaza, Zambézia, and Nampula. Sixteen outpatient primary care health facilities equipped with simplified Audiometry and/or ECG devices (specifically, SHOEBOX Audiometer® and/or SmartHeart Pro ECG®) installed for at least 6 months before the study initiation were selected. The data was collected using in-depth interviews (IDI) and Focus Group Discussions (FGD) techniques. Interviews were audio-recorded, transcribed verbatim in Portuguese, coded, and analyzed using Nvivo 12 software®. We generated two themes and fit our results into a conceptual framework consisting of three domains in the implementation of technological innovations in health. Results A total of 16 healthcare providers and 91 people undergoing treatment for DR-TB were enrolled in the study. Most people with DR-TB had experienced audiometry testing and demonstrated a good understanding of the assessments. Conversely, while most healthcare providers demonstrated robust knowledge of the importance of both audiometry and ECG assessments, they were not confident in managing ECG devices and interpreting the results. Conclusions While healthcare providers demonstrated a consolidated understanding of the importance of audiometry, the limited number of devices and lack of training were constraints, impeding optimal usage and service delivery

Logistic regression predicting NVP RAM adjusted for independent variables of interest.

<p>Data are number (%); mean (standard deviation).</p><p>* The following independent variables were included in the multiple logistic adjusted regression analysis: child gender, child age, mother exposure to ARV, mother CD4 count, maternal duration of exposure to ARVs.</p><p>Values in bold denote statistical significance.</p><p>ART, antiretroviral therapy; CI, Confidence Interval; OR, Odds Ratio; NVP RAM, nevirapine resistance associated mutations; MTCT, mother-to-child-transmission; mm³, cubic millilitre.</p><p>Logistic regression predicting NVP RAM adjusted for independent variables of interest.</p

Profile of NVP resistance associated mutations (RAM).

<p>Percentages were calculated based on the total number of NVP RAM (n = 66). K103N and Y181C were the most frequent NVP RAM (24.2% and 22.7% of the samples, respectively).</p

Profile of drug resistance associated mutations by ARV class.

<p>Percentages were calculated based on the total number of RAM found for each ARV class (NNTRI = 74, NRTI = 54 and PI = 8).</p

Mother and child socio-demographic and clinical characteristics among the population with resistance test results.

<p>Data are number (%), median (range).</p><p>AZT, zidovudine; sd-NVP, single-dose nevirapine; MTCT, mother-to-child transmission; ARVs, antiretrovirals; ART, antiretroviral therapy; mm³, cubic millilitre.</p><p>^†The mother’s first-line ART regimen included AZT + 3TC + NVP. The maternal ARV prophylaxis consisted of antepartum daily AZT as early as 14 weeks of gestation, sd-NVP at onset of labour and twice daily AZT + 3TC for 7 days postpartum.</p><p>Mother and child socio-demographic and clinical characteristics among the population with resistance test results.</p

Tuberculosis infection risk, preventive therapy care cascade and incidence of tuberculosis disease in healthcare workers at Maputo Central Hospital.

BackgroundMozambican healthcare workers have high rates of latent and active tuberculosis, but occupational screening for tuberculosis is not routine in this setting. Furthermore, the specificity of tuberculin skin testing in this population compared with interferon gamma release assay testing has not been established.MethodsThis study was conducted among healthcare workers at Maputo Central Hospital, a public teaching quaternary care hospital in Mozambique. With a cross sectional study design, risk factors for tuberculosis were assessed using multivariable logistic regression. The care cascade is reported for participants who were prescribed six months of isoniazid preventive therapy for HIV or highly reactive testing for latent tuberculosis infection. The agreement of interferon-gamma release assay results with positive tuberculin skin testing was calculated.ResultsOf 690 screened healthcare workers, three (0.4%) had active tuberculosis and 426 (61.7%) had latent tuberculosis infection. Less education, age 35-49, longer hospital service, and work in the surgery department were associated with increased likelihood of being tuberculosis infected at baseline (p&nbsp;&lt; 0.05). Sex, Bacillus Calmette-Guerin vaccination, HIV, outside tuberculosis contacts, and professional category were not. Three new cases of active tuberculosis developed during the follow-up period, two while on preventive therapy. Among 333 participants offered isoniazid preventive therapy, five stopped due to gastrointestinal side effects and 181 completed treatment. For HIV seropositive individuals, the agreement of interferon gamma release assay positivity with positive tuberculin skin testing was 50% among those with a quantitative skin test result of 5-10 mm, and among those with a skin test result ≥10 mm it was 87.5%. For HIV seronegative individuals, the agreement of interferon gamma release assay positivity with a tuberculin skin test result of 10-14 mm was 63.6%, and for those with a quantitative skin test result ≥15 mm it was 82.2%.ConclusionsThere is a high prevalence of tuberculosis infected healthcare workers at Maputo Central Hospital. The surgery department was most heavily affected, suggesting occupational risk. Isoniazid preventive therapy initiation was high and just over half completed therapy. An interferon gamma release assay was useful to discern LTBI from false positives among those with lower quantitative tuberculin skin test results

Tuberculosis infection risk, preventive therapy care cascade and incidence of tuberculosis disease in healthcare workers at Maputo Central Hospital

Abstract Background Mozambican healthcare workers have high rates of latent and active tuberculosis, but occupational screening for tuberculosis is not routine in this setting. Furthermore, the specificity of tuberculin skin testing in this population compared with interferon gamma release assay testing has not been established. Methods This study was conducted among healthcare workers at Maputo Central Hospital, a public teaching quaternary care hospital in Mozambique. With a cross sectional study design, risk factors for tuberculosis were assessed using multivariable logistic regression. The care cascade is reported for participants who were prescribed six months of isoniazid preventive therapy for HIV or highly reactive testing for latent tuberculosis infection. The agreement of interferon-gamma release assay results with positive tuberculin skin testing was calculated. Results Of 690 screened healthcare workers, three (0.4%) had active tuberculosis and 426 (61.7%) had latent tuberculosis infection. Less education, age 35–49, longer hospital service, and work in the surgery department were associated with increased likelihood of being tuberculosis infected at baseline (p < 0.05). Sex, Bacillus Calmette-Guerin vaccination, HIV, outside tuberculosis contacts, and professional category were not. Three new cases of active tuberculosis developed during the follow-up period, two while on preventive therapy. Among 333 participants offered isoniazid preventive therapy, five stopped due to gastrointestinal side effects and 181 completed treatment. For HIV seropositive individuals, the agreement of interferon gamma release assay positivity with positive tuberculin skin testing was 50% among those with a quantitative skin test result of 5-10 mm, and among those with a skin test result ≥10 mm it was 87.5%. For HIV seronegative individuals, the agreement of interferon gamma release assay positivity with a tuberculin skin test result of 10-14 mm was 63.6%, and for those with a quantitative skin test result ≥15 mm it was 82.2%. Conclusions There is a high prevalence of tuberculosis infected healthcare workers at Maputo Central Hospital. The surgery department was most heavily affected, suggesting occupational risk. Isoniazid preventive therapy initiation was high and just over half completed therapy. An interferon gamma release assay was useful to discern LTBI from false positives among those with lower quantitative tuberculin skin test results