Implementing HbA1c monitoring in sub-Saharan Africa: Lessons learnt from a pilot project in Mozambique.

Aims: We aimed to evaluate lesson learnt from a pilot project in Mozambique focused on point-of-care (POC) HbA1c testing for diabetes management in primary health care facilities. Methods: Over a three-year period, several health centers were equipped with POC HbA1c testing machines. The evaluation involved 12 months of data collection, interviews with patients and staff, and regular supervision visits. Results: The project screened over 22,000 individuals and provided HbA1c testing to 2362 diabetes patients. Among the analyzed results, 65.7 % had HbA1c levels below 7 %, 10.9 % between 7 % and 8.5 %, and 23.4 % above 8.5 %. POC testing showed advantages such as reduced costs and improved workload management. Conclusions: Limited access to HbA1c testing remains a challenge in African countries. The pilot project demonstrated the feasibility of POC HbA1c testing and highlighted the need for increased efforts to make it more widely available, leading to improved diabetes management and patient outcomes.

Screening approaches for cervical cancer in Mozambique in HIV positive and negative women.

OBJECTIVE: Cervical cancer (CC) is a global health issue, in Mozambique, 5300 new cases and 3800 deaths are reported each year. The WHO recommends the introduction of HPV molecular testing for CC screening, but Mozambique uses an approach based on visual inspection with acetic acid (VIA). This study aims to evaluate the feasibility of high-risk HPV (hrHPV) testing compared to actual approaches in Mozambique. METHODS: An observational study was carried out in the DREAM center in Zimpeto, Mozambique. Women aged 30-55 were included. HPV testing was performed with the Cobas HPV test. They were then screened with the current national recommendations based on VIA. Cryotherapy was performed on-site or referred for colposcopy if necessary. RESULTS: In the period, 1207 women were enrolled, 47.8% HIV+; 124 (10.3%) VIA+, and HPV DNA test was positive in 325 (26.9%) women. HPV positivity rates were higher in HIV-infected women. In the sample, 52.8% of the 124 VIA+ women were HPV uninfected and underwent unnecessary cryotherapy or colposcopy. Meanwhile, 24.7% of the 1083 VIA- women were actually HPV infected. In comparison, a screen, triage and treat approach based on hrHPV testing would only test and treat the 325 HPV-infected women. CONCLUSION: The study found high rates of hrHPV infection, particularly in HIV-positive women, with many concurrent or multiple infections. The current screening method misses important hrHPV infections and results in many unnecessary treatments. These results support the use of HPV molecular testing as the initial screening test for CC.

Burden of headache in a HIV-positive population of sub-Saharan Africa.

BACKGROUND: About 26 million people are living with HIV in sub-Saharan Africa. The DREAM programme in sub-Saharan Africa provides free healthcare for HIV/AIDS and a range of chronic non-communicable diseases. HIV is a risk factor for neurological non-communicable diseases including stroke and epilepsy, which themselves are associated with headache, and HIV may be a direct risk factor for headache. We investigated the prevalence and burden of headache in a HIV+ population in sub-Saharan Africa. METHODS: At the DREAM Centre in Blantyre, Malawi, a low-income country with a population of 19 million and 9.2% HIV prevalence, a structured questionnaire was administered by a trained lay interviewer to consecutively attending HIV+ patients aged 6-65 years. All were monitored with regular viral load detection. RESULTS: Of 513 eligible patients invited, 498 were included (mean age 34.1 ± 12.8 years; 72% females; 15 declined). All were on antiretroviral treatment, with viral load undetectable in 83.9%. The 1-year prevalence of headache was 80.3% (females 83.6%, males 71.9%); 3.8% had ≥15 headache days/month, 1.4% had probable medication-overuse headache. Mean overall headache frequency was 4.4 ± 5.4 days/month. Those reporting headache lost means of 2.3% of paid workdays and 3.3% of household workdays because of headache. Only one third had sought advice for their headache. CONCLUSIONS: Headache is very prevalent among HIV+ patients in Malawi, imposing additional burden and costs on individuals and the community. Management of headache disorders should be implemented in HIV centres, as it is for other chronic non-communicable diseases.

Early detection of poor glycemic control in patients with diabetes mellitus in sub-Saharan Africa: a cohort study in Mozambique.

Introduction: WHO estimates 422 million cases of diabetes mellitus worldwide. Mozambique has the second-highest mortality related to DM in the African region.Objectives of the present study are to provide data about a DM care service in Mozambique and to evaluate early outcomes of treatment. Methods: The new patients diagnosed with DM in a two-years period in a health centre in Maputo (Mozambique) were included in a retrospective cohort study. Fasting blood glucose (FBG), waist circumference (WC) and BMI were collected at baseline and after three months. Results: 188 patients were enrolled. Median BMI, WC and FBG at baseline were respectively 28 kg/m2(Inter Quartile Range [IQR]23.4-31.8), 98cm (IQR 87-105) and 209mg/dL (IQR 143-295). A non-pharmacological intervention was prescribed for six patients, while 182 patients received metformin 500 mg b.i.d. FBG was significantly reduced at control (226[±103.7]mg/dL vs 186[±93.2]mg/dL, p<0.000); however, glycemic control was reached in 74 patients (39.4%); not controlled patients changed regimen. Elderly patients had a higher glycemic control (adjusted Odds Ratio 2.50, 95% CI 1.11-5.06, p=0.002). Conclusion: Strategies for early detection of scarce glycemic control are feasible in Mozambique and could lead to prompt regimen switch; an invasive therapeutic approach could be preferable in selected cases to achieve control.

Pandemics and Burden of Stroke and Epilepsy in Sub-Saharan Africa: Experience from a Longstanding Health Programme.

Eighty percent of people with stroke live in low- to middle-income nations, particularly in sub-Saharan Africa (SSA) where stroke has increased by more than 100% in the last decades. More than one-third of all epilepsy-related deaths occur in SSA. HIV infection is a risk factor for neurological disorders, including stroke and epilepsy. The vast majority of the 38 million people living with HIV/AIDS are in SSA, and the burden of neurological disorders in SSA parallels that of HIV/AIDS. Local healthcare systems are weak. Many standalone HIV health centres have become a platform with combined treatment for both HIV and noncommunicable diseases (NCDs), as advised by the United Nations. The COVID-19 pandemic is overwhelming the fragile health systems in SSA, and it is feared it will provoke an upsurge of excess deaths due to the disruption of care for chronic diseases such as HIV, TB, hypertension, diabetes, and cerebrovascular disorders. Disease Relief through Excellent and Advanced Means (DREAM) is a health programme active since 2002 to prevent and treat HIV/AIDS and related disorders in 10 SSA countries. DREAM is scaling up management of NCDs, including neurologic disorders such as stroke and epilepsy. We described challenges and solutions to address disruption and excess deaths from these diseases during the ongoing COVID-19 pandemic.

Hypercholesterolemia and related risk factors in a cohort of patients with diabetes and hypertension in Maputo, Mozambique.

INTRODUCTION: some studies reported that 25.5% of African population presents hypercholesterolemia; however, epidemiology of hypercholesterolemia in Africa is poorly described. Mozambique is experiencing a constant growth of non-communicable diseases, but scarce data are available about hypercholesterolemia. Our study aims at describing the prevalence of hypercholesterolemia in patients with diabetes and hypertension in Mozambique and investigate possible risk factors. METHODS: we conducted a cross-sectional study involving all the patients diagnosed with hypertension and/or diabetes from June 2018 to November 2020 in the Zimpeto DREAM Centre (Maputo, Mozambique). For each patient, anthropometric, clinical and laboratory data were collected. Hypercholesterolemia was defined as total blood cholesterol >200 mg/dL. Univariable and multivariable analysis were perfumed. RESULTS: a total of 885 patients were included, 76.2% (n=674) female. Hypertension alone was diagnosed in 670 (75.7%) patients, diabetes in 109 (12.3%) patients and 106 (11.9%) both diseases. Hypercholesterolemia was present in 410 (46.3%) patients and it was more prevalent in patients diagnosed with both diabetes and hypertension (52.8%), as compared to the patients diagnosed with hypertension (46.9%) or diabetes alone (36.7%). In the multivariable analysis, the only factors independently associated with hypercholesterolemia were female sex (aOR 1.77, 95% CI 1.26-2.48, p=0.001) and a body mass index >25kg/m2 (aOR 1.50, 95% CI 1.11-2.04, p=0.008). CONCLUSION: our results highlight the need for a specific focus on female and obese/overweight patients, especially if diagnosed with both hypertension and diabetes, to promptly detect metabolic disorders and establish temporary preventive measures for cardiovascular events.

High-sensitivity C-reactive protein in HIV care: Tuberculosis diagnosis and short-term mortality in a cohort of Kenyan HIV patients in the DREAM programme.

OBJECTIVE: Tuberculosis (TB) is the leading cause of death in HIV-positive people. In Kenya, 140 000 new TB cases occurred in 2019, and 13 000 HIV-positive patients died due to TB. The objective of this study was to investigate the role of high-sensitivity C-reactive protein (HS-CRP) in TB diagnosis and the prediction of mortality in HIV-positive patients. METHODS: The IDEA-TB Study enrolled HIV-positive adult patients attending three DREAM centres in Kenya who were suspected of having TB. A lateral flow urine lipoarabinomannan assay (LF-LAM), serum HS-CRP, and GeneXpert MTB/RIF assay (Xpert MTB/RIF) were performed. Six-month survival was evaluated. RESULTS: A total of 574 patients were enrolled. The median (interquartile range) age, body mass index, and CD4 count were 45 years (37-54 years), 20.5 kg/m2 (18.5-23.69 kg/m2), and 477 cells/mL (290-700 cells/mL), respectively. TB was confirmed in 87 (15.2%) patients. Concordance between the Xpert MTB/RIF and LF-LAM tests was 87.1%. HS-CRP was higher in TB patients (35.39 mg/l vs 9.21 mg/l). Malnutrition and elevated HS-CRP were associated with TB: odds ratio (OR) 2.5 (95% confidence interval (CI) 1.14-5.72) and OR 6.6 (95% CI 3.87-11.52), respectively. Nine (1.6%) patients died during follow-up. No single factor was associated with mortality. Only the combination of malnutrition and elevated HS-CRP was highly predictive of death (odds ratio (OR) 9.8, 95% CI 1.88-50.95); the association was stronger in TB patients (33.3% vs 1.0%; OR 47.6, 95% CI 7.03-322.23). CONCLUSION: TB diagnosis in HIV-positive patients remains challenging. HS-CRP could play a role in predicting early mortality in symptomatic patients.

Low mortality rates at two years in HIV-infected individuals undergoing systematic tuberculosis testing with rapid assays at initiation of antiretroviral treatment in Mozambique.

BACKGROUND: Few studies have evaluated the mortality rate in individuals with HIV initiating antiretroviral therapy (ART), undergoing screening with combined or repeated rapid tests for tuberculosis (TB). METHODS: All individuals with HIV starting ART, irrespective of the presence of TB-related symptoms, received two consecutive Xpert tests plus a rapid test for the detection of mycobacterial lipoarabinomannan in urine (LAM). Mortality was evaluated by Kaplan-Meier analysis using the log-rank test in univariate analyses and Cox regression models with time-dependent covariates in multivariate analyses. RESULTS: Among 972 individuals screened with combined tests, 98 (10.1%) tested positive for TB with Xpert, LAM, or both. At the end of the study, 780 (80.2%) had completed 2 years of follow-up, 39 (4.0%) had died, and 153 (15.7%) were lost to follow-up. In the multivariate analyses, the factors significantly associated with mortality were missed ART (hazard ratio (HR) 7.05, 95% confidence interval (CI) 2.33-21.35), symptomatic HIV disease (WHO-HIV stage >1) (HR 3.31, 95% CI 1.28-8.54), and low CD4 count (<200/mm3) (HR 2.72, 95% CI 1.21-6.13), with no significant effect of TB status. In the subgroup of the 98 TB-positive individuals, only missed ART (HR 4.12, 95% CI 1.03-16.46) and missed anti-TB treatment (HR 9.25, 95% CI 2.65-32.28) were significantly associated with mortality. CONCLUSIONS: A low mortality rate was observed among individuals with HIV undergoing systematic testing for TB at initiation of ART. After adjusting for confounders, mortality was significantly associated with missed ART, advanced disease, and missed anti-TB treatment. These findings reinforce the need to promote early diagnosis of HIV and the adoption of screening strategies for TB that prevent presentation with severe disease.

Elimination of Mother-To-Child Transmission of HIV Infection: The Drug Resource Enhancement against AIDS and Malnutrition Model.

The Drug Resource Enhancement against AIDS and Malnutrition Program (DREAM) gathered professionals in the field of Elimination of HIV-Mother-To-Child Transmission (EMTCT) in Maputo in 2013 to discuss obstacles and solutions for the elimination of HIV vertical transmission in sub-Saharan Africa. During this workshop, the benefits of administrating combined antiretroviral therapy (cART) to HIV positive women from pregnancy throughout breastfeeding were reviewed. cART is capable of reducing vertical transmission to less than 5% at 24 months of age, as well as maternal mortality and infant mortality in both HIV infected and exposed populations to levels similar to those of uninfected individuals. The challenge for programs targeting eMTCT in developing countries is retention in care and treatment adherence. Both are intrinsically related to the model of care. The drop-out from eMTCT programs before cART initiation ranges from 33%-88% while retention rates at 18-24 months are less than 50%. Comprehensive strategies including peer-to-peer education, social support and laboratory monitoring can reduce refusals to less than 5% and attain retention rates approaching 90%. Several components of the model of care for reduction of HIV-1 MTCT are feasible and implementable in scale-up strategies. A review of this model of care for HIV eMTCT is provided.

Reduction of maternal mortality with highly active antiretroviral therapy in a large cohort of HIV-infected pregnant women in Malawi and Mozambique.

BACKGROUND: HIV infection is a major contributor to maternal mortality in resource-limited settings. The Drug Resource Enhancement Against AIDS and Malnutrition Programme has been promoting HAART use during pregnancy and postpartum for Prevention-of-mother-to-child-HIV transmission (PMTCT) irrespective of maternal CD4 cell counts since 2002. METHODS: Records for all HIV+ pregnancies followed in Mozambique and Malawi from 6/2002 to 6/2010 were reviewed. The cohort was comprised by pregnancies where women were referred for PMTCT and started HAART during prenatal care (n = 8172, group 1) and pregnancies where women were referred on established HAART (n = 1978, group 2). RESULTS: 10,150 pregnancies were followed. Median (IQR) baseline values were age 26 years (IQR:23-30), CD4 count 392 cells/mm(3) (IQR:258-563), Viral Load log10 3.9 (IQR:3.2-4.4), BMI 23.4 (IQR:21.5-25.7), Hemoglobin 10.0 (IQR: 9.0-11.0). 101 maternal deaths (0.99%) occurred during pregnancy to 6 weeks postpartum: 87 (1.1%) in group 1 and 14 (0.7%) in group 2. Mortality was 1.3% in women with

Immunologic response to highly active antiretroviral therapy and mortality reduction in a cohort of human immunodeficiency virus-positive persons in Mozambique.

Since February 2002, the Drug Resources Enhancement against AIDS and Malnutrition Program has provided highly active antiretroviral therapy (HAART) and immunologic and virologic monitoring free of charge. We conducted a cohort study of persons infected with human immunodeficiency virus in Mozambique. Only persons treated with HAART with available CD4 cell counts at baseline and ≥ 1 CD4 cell count after HAART were included. Survival analysis was applied to evaluate the prognostic value of CD4 cell counts measured at three months. Possible confounders were considered. A total of 753 persons who started HAART included; 59% were females. Median age was 34 years (range = 16-67 years), and the median CD4 cell count at baseline was 172 cells/mm3 (interquartile range = 87-261 cells/mm3, range = 0-1,322 cells/mm3). Overall, 105 persons (14%) died. Of these persons 54 (51%) developed AIDS before they died; 25 (3%) died during the first three months. After three months of therapy, the individual median CD4 cell count change from the baseline value was +101 cells/mm3 (interquartile range = +27 to +187 cells/mm3, range = -723 to +310 cells/mm3). A median CD4 increment of 100 cells/mm3 in three months was associated with a mortality reduction of 50% compared with an increase of < 50 cells (relative hazard of death adjusted for baseline CD4 cell count = 0.54, 95% confidence interval = 0.30-0.95). A good initial response to HAART was associated with a significant reduction of mortality. This finding supports the effectiveness of HAART in resource-poor settings.

Correlation between HIV-1 viral load quantification in plasma, dried blood spots, and dried plasma spots using the Roche COBAS Taqman assay.

BACKGROUND: The use of simplified methods for viral load determination could greatly increase access to treatment monitoring of HIV patients in resource-limited countries. OBJECTIVE: The aim of the present study was to optimize and evaluate the performance of the Roche COBAS Taqman assay in HIV-RNA quantification from dried blood spots (DBS) and dried plasma spots (DPS). STUDY DESIGN: EDTA blood samples from 108 HIV-infected women were used to prepare 129 DBS and 76 DPS on Whatman 903 card. DBS and DPS were stored at -20 degrees C. HIV-1 RNA was extracted from DBS/DPS using the MiniMAG system (bioMerieux). Amplification and detection were performed using the Roche COBAS TaqMan assay. Plasma viral load results were used as standard. RESULTS: There was a high correlation between measures of viral load in plasma and in DBS/DPS (r=0.96 and 0.85 respectively, P<0.001). Overall, viral load values in DBS and DPS tended to be lower than in plasma with mean (SD) differences of 0.32 log(0.22) for DBS and of 0.35 (0.33) for DPS. Detection rates were 96.4% for DBS and 96.1% for DPS in samples with corresponding plasma values >3.0 log copies/ml. Samples with HIV-RNA below 50 copies/ml were correctly identified in 18/19 DBS and in 7/7 DPS. CONCLUSIONS: Both DBS and DPS provided results highly correlated to the plasma values. High detection rate was obtained with both DBS and DPS when HIV-RNA was >3.0 log copies/ml. Our results support the use of DBS/DPS to detect virologic failure in resource-limited settings.

Comparison of HIV type 1 sequences from plasma, cell-free breast milk, and cell-associated breast milk viral populations in treated and untreated women in Mozambique.

We analyzed the sequences of the HIV viral populations obtained from plasma, cell-free breast milk, and breast milk cells of HAART-treated (23) and untreated (30) HIV-infected women to obtain information about the origin of the breast milk virus. Sequence analyses of viruses were performed using the TruGene HIV-1 assay. Direct sequences of the reverse transcriptase (RT) and protease (PR) genes were analyzed using the Phylip 3.68 suite of sequence analysis program and pairwise evolutionary distances were calculated with the Kimura two parameter model for estimation of distances. We found that the genetic distances between the plasma and the cell-free breast milk viruses and between the cell-free and cell-associated breast milk viruses for RT were higher in HAART-receiving women than in untreated women, suggesting viral evolution under selective drug pressure in breast milk. Our data support the hypothesis of the presence of an actively replicating viral population in the breast milk compartment, distinct from that present in plasma.

Incidence and predictors of death, retention, and switch to second-line regimens in antiretroviral- treated patients in sub-Saharan African Sites with comprehensive monitoring availability.

BACKGROUND: Antiretroviral treatment programs in sub-Saharan Africa have high rates of early mortality and loss to follow-up. Switching to second-line regimens is often delayed because of limited access to laboratory monitoring. METHODS: Retrospective analysis was performed of a cohort of adults who initiated a standard first-line antiretroviral treatment at 5 public sector sites in 3 African countries. Monitoring included routine CD4 cell counts, human immunodeficiency virus RNA measures, and records of whether appointments were kept. Incidence and predictors of death, loss to follow-up, and switch to second-line regimens were analyzed by time-to-event approaches. RESULTS: A total of 3749 patients were analyzed; at baseline, 37.1% were classified as having World Health Organization disease stage 3 or 4, and the median CD4 cell count was 192 cells/mL. First-line regimens were nevirapine based in 96.5% of patients; 17.7% of patients attended <95% of their drug pickup appointments. During 4545 person-years of follow-up, mortality was 8.6 deaths per 100 person-years and was predicted by lower baseline CD4 cell count, lower hemoglobin level, and lower body mass index (calculated as weight in kilograms divided by the square of height in meters); more-advanced clinical stage of infection; male sex; and more missed drug pickup appointments. Dropouts (which accrued at a rate of 2.1 dropouts per 100 person-years) were predicted by a lower body mass index, more missed visits and missed drug pickup appointments, and later calendar year. Incidence of switches to second-line regimens was 4.9 per 100 person-years; increased hazards were observed with lower CD4 cell count and earlier calendar year at baseline. In patients who switched, virological failure was predicted by combined clinical and CD4 criteria with 74% sensitivity and 30% specificity. CONCLUSIONS: In an antiretroviral treatment program employing comprehensive monitoring, the probability of switching to second-line therapy was limited. Regular pickup of medication was a predictor of survival and was also strongly predictive of patient retention.

Single-nucleotide polymorphisms in human beta-defensin-1 gene in Mozambican HIV-1-infected women and correlation with virologic parameters.

We analyzed single nucleotide polymorphisms in the 5'-untranslated region (-44C/G and -52G/A) of the beta-defensin-1 gene in 78 Mozambican HIV-1-infected mothers. We observed significantly lower levels of HIV-1 RNA in breast milk, but not in plasma, in women with the -52GG genotype versus women with the -52GA and -52AA genotypes, supporting the hypothesis that different expression of beta-defensins could have an impact on viral replication in breast milk.

Evaluating adherence to highly active antiretroviral therapy with use of pill counts and viral load measurement in the drug resources enhancement against AIDS and malnutrition program in Mozambique.

BACKGROUND: Maintaining treatment adherence among the growing number of patients receiving antiretroviral treatment in Africa is a dramatic challenge. The objective of our study was to explore the results of a computerized pill count method and to test the validity, sensitivity, and specificity of this method with respect to viral load measurement in an African setting. METHODS: We performed a prospective, observational study involving patients who received first-line highly active antiretroviral therapy in Mozambique from 1 April 2005 through 31 March 2006. Enrolled patients had received treatment for at least 3 months before the study. For defining treatment adherence levels, pill counts were used, and the results were analyzed with viral load measurements at the end of the observation period. RESULTS: The study involved 531 participants. During the 12 months of observation, 137 patients left the program or discontinued first-line therapy. Of the remaining 394 patients, 284 (72.1%) had >95% treatment adherence; of those 284 patients, 274 (96.5%) had a final viral load <1000 copies/mL. A Cox proportional hazards analysis revealed that the relationship between >95% treatment adherence and the final viral load was closer than that between >90% treatment adherence and viral load. CONCLUSIONS: Treatment adherence >95% maximizes the results of the nonnucleoside reverse-transcriptase inhibitor-based regimen. The pill count method appears to be a reliable and economic tool for monitoring treatment adherence in resource-limited settings.