Comparison of CG, CKD-EPI[AS] and CKD-EPI[ASR] equations to estimate glomerular filtration rate and predict mortality in treatment naïve people living with HIV in Zimbabwe.

BACKGROUND: Renal impairment in people living with HIV (PWH) in Sub-Saharan Africa is common and associated with increased morbidity and mortality. The ideal equation to estimate glomerular filtration rate (eGFR) in this population remains unclear. That which best predicts clinical risk may be the most appropriate while validation studies are awaited. Here we compare the Cockcroft-Gault (CG), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI[ASR]) and the CKD-EPI equation with the race coefficient removed (CKD-EPI[AS]), in a population of anti-retroviral therapy (ART) naïve PWH in Zimbabwe to assess which equation best predicts mortality. METHODS: A retrospective cohort study of treatment naïve PWH at the Newlands Clinic in Harare, Zimbabwe was completed. The study included all patients commencing ART between 2007 and 2019. Predictors of mortality were assessed by multivariable logistic regression. RESULTS: A total of 2991 patients were followed-up for a median of 4.6 years. The cohort was 62.1% female, with 26.1% of patients having at least one comorbidity. The CG equation identified 21.6% of patients as having renal impairment compared with 17.6% with CKD-EPI[AS] and 9.3% with CKD-EPI[ASR]. There was a mortality rate of 9.1% across the study period. The highest mortality risk was seen in those with renal impairment as determined by the CKD-EPI[ASR] equation for both eGFR < 90 and eGFR < 60 with OR 2.97 (95%CI 1.86-4.76) and OR 10.6 (95%CI 3.15-18.04) respectively. CONCLUSION: In treatment naïve PWH in Zimbabwe, the CKD-EPI[ASR] equation identifies patients at highest risk of mortality when compared to the CKD-EPI[AS] and CG equations.

Tracing People Living With Human Immunodeficiency Virus Who Are Lost to Follow-up at Antiretroviral Therapy Programs in Southern Africa: A Sampling-Based Cohort Study in 6 Countries.

BACKGROUND: Attrition threatens the success of antiretroviral therapy (ART). In this cohort study, we examined outcomes of people living with human immunodeficiency virus (PLHIV) who were lost to follow-up (LTFU) during 2014-2017 at ART programs in Southern Africa. METHODS: We confirmed LTFU (missed appointment for ≥60 or ≥90 days, according to local guidelines) by checking medical records and used a standardized protocol to trace a weighted random sample of PLHIV who were LTFU in 8 ART programs in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, 2017-2019. We ascertained vital status and identified predictors of mortality using logistic regression, adjusted for sex, age, time on ART, time since LTFU, travel time, and urban or rural setting. RESULTS: Among 3256 PLHIV, 385 (12%) were wrongly categorized as LTFU and 577 (17%) had missing contact details. We traced 2294 PLHIV (71%) by phone calls, home visits, or both: 768 (34% of 2294) were alive and in care, including 385 (17%) silent transfers to another clinic; 528 (23%) were alive without care or unknown care; 252 (11%) had died. Overall, the status of 1323 (41% of 3256) PLHIV remained unknown. Mortality was higher in men than women, higher in children than in young people or adults, and higher in PLHIV who had been on ART <1 year or LTFU ≥1 year and those living farther from the clinic or in rural areas. Results were heterogeneous across sites. CONCLUSIONS: Our study highlights the urgent need for better medical record systems at HIV clinics and rapid tracing of PLHIV who are LTFU.

Predictors of renal impairment and proteinuria after commencement of antiretroviral therapy in a Zimbabwean HIV cohort.

BACKGROUND: Renal disease prevalence varies widely amongst reported cohorts of people living with HIV (PLWHIV) in sub-Saharan Africa. Renal function testing is not routine in those commencing antiretroviral therapy (ART) in the region, however. Further data on renal disease prevalence and the change associated with ART use are therefore needed. AIM: To explore changes in renal function and associated predictors after 1 year of ART in an adult cohort of PLWHIV from Zimbabwe. METHODS: A retrospective analysis of patients who attended the Newlands Clinic between January 2007 and September 2019. Eligible patients were aged ≥18 years and had measures of serum creatinine at baseline and after 1 year of ART. Predictors of renal function change were assessed by multiple linear regression. RESULTS: 1729 patients were eligible for inclusion. Median age was 36 years (IQR 30-43) and 62.8% were female. After 1 year of ART, the proportion of patients with an estimated glomerular filtration rate (eGFR) <60 ml/min/1.732 did not significantly change (2.0% vs. 1.2%; p = 0.094), but there was a decrease in the proportion of patients with proteinuria (11.0% vs. 5.6%; p < 0.001). Hypertension (B = -6.43; 95% CI -8.97 to -3.89; p < 0.001) and baseline proteinuria (B = -7.33; 95% CI -10.25 to -4.42; p < 0.001) were negative predictors of change in eGFR from baseline, whereas diabetes status was not associated (p = 0.476). CONCLUSION: Proteinuria was common, but its prevalence halved after 1 year of ART. Screening for hypertension could be a simple way to identify patients at risk of renal function decline.

Comparison of predictors for early and late mortality in adults commencing HIV antiretroviral therapy in Zimbabwe: a retrospective cohort study.

BACKGROUND: People living with HIV (PLWHIV) commencing antiretroviral therapy (ART) in sub-Saharan Africa experience significant mortality within the first year. Previously, identified risk factors for mortality may be biased towards these patients, as compared to those who experience late mortality. AIM: To compare risk factors for early and late mortality in PLWHIV commencing ART. METHODS: A retrospective cohort study of ART-naïve patients aged ≥ 18 years from an outpatient HIV clinic in Zimbabwe. Data were collected between January 2010 and January 2019. Predictors for early (≤ 1 year) and late mortality (> 1 year) were determined by multivariable cox proportional hazards analyses, with patients censored at 1 year and landmark analysis after 1 year, respectively. RESULTS: Three thousand and thirty-nine PLWHIV were included in the analysis. Over a median follow-up of 4.6 years (IQR 2.5-6.9), there was a mortality rate of 8.8%, with 50.4% of deaths occurring within 1 year. Predictors of early mortality included CD4 count < 50 cells/µL (HR 1.84, 95% CI 1.24-2.72, p < 0.01), WHO Stage III (HR 2.05, 95% CI 1.28-3.27, p < 0.01) or IV (HR 2.83, 95% CI 1.67-4.81, p < 0.01), and eGFR < 90 mL/min/1.73 m2 (HR 2.48, 95% CI 1.56-3.96, p < 0.01). Other than age (p < 0.01), only proteinuria (HR 2.12, 95% CI 1.12-4.01, p = 0.02) and diabetes mellitus (HR 3.51, 95% CI 1.32-9.32, p = 0.01) were associated with increased risk of late mortality. CONCLUSIONS: Traditional markers of mortality risk in patients commencing ART appear to be limited to early mortality. Proteinuria and diabetes are some of the few predictors of late mortality, and should be incorporated into routine screening of patients commencing ART.

Leveraging human resources for outbreak analysis: lessons from an international collaboration to support the sub-Saharan African COVID-19 response.

Emerging infectious diseases are a growing threat in sub-Saharan African countries, but the human and technical capacity to quickly respond to outbreaks remains limited. Here, we describe the experience and lessons learned from a joint project with the WHO Regional Office for Africa (WHO AFRO) to support the sub-Saharan African COVID-19 response.In June 2020, WHO AFRO contracted a number of consultants to reinforce the COVID-19 response in member states by providing actionable epidemiological analysis. Given the urgency of the situation and the magnitude of work required, we recruited a worldwide network of field experts, academics and students in the areas of public health, data science and social science to support the effort. Most analyses were performed on a merged line list of COVID-19 cases using a reverse engineering model (line listing built using data extracted from national situation reports shared by countries with the Regional Office for Africa as per the IHR (2005) obligations). The data analysis platform The Renku Project ( https://renkulab.io ) provided secure data storage and permitted collaborative coding.Over a period of 6 months, 63 contributors from 32 nations (including 17 African countries) participated in the project. A total of 45 in-depth country-specific epidemiological reports and data quality reports were prepared for 28 countries. Spatial transmission and mortality risk indices were developed for 23 countries. Text and video-based training modules were developed to integrate and mentor new members. The team also began to develop EpiGraph Hub, a web application that automates the generation of reports similar to those we created, and includes more advanced data analyses features (e.g. mathematical models, geospatial analyses) to deliver real-time, actionable results to decision-makers.Within a short period, we implemented a global collaborative approach to health data management and analyses to advance national responses to health emergencies and outbreaks. The interdisciplinary team, the hands-on training and mentoring, and the participation of local researchers were key to the success of this initiative.

Gynecomastia in HIV-positive adult men receiving efavirenz-based antiretroviral therapy at Newlands clinic, Harare, Zimbabwe.

BACKGROUND: Gynecomastia is known to occur in some men taking an efavirenz-based antiretroviral therapy (ART) regimen. However, the incidence and outcomes of gynecomastia are not known in Zimbabwe. We described the characteristics and outcomes of gynecomastia among male patients on an efavirenz-based ART regimen. METHODS: We conducted a retrospective cohort review of data of all male patients aged ≥18 years taking an efavirenz-based regimen at Newlands Clinic, Harare, Zimbabwe before 31 March 2017. The primary outcome was gynecomastia as defined by breast/nipple enlargement reported by patient and confirmed by clinical palpation. Routinely collected data on demographics, baseline CD4, body mass index, duration on efavirenz, clinical presentation and outcomes were extracted from the clinic database and analysed using STATA 12.1. We investigated for any associations with concomitant medicines using cox regression. RESULTS: We analysed data for 1432 men with a median age of 40 years (IQR: 33-48). Half of the patients were in WHO stage 1 at ART commencement. Median body mass index and CD4 count at efavirenz commencement was 21 (IQR: 19-23) and 260 cells/mm3 (IQR: 126-412) respectively. The incidence of gynecomastia was 22/1000 person-years (IQR: 17.3-27.8). Over half of the cases (58%) were bilateral and 75% of all cases developed within two years of starting efavirenz. There were no significant associations with concomitant use of isoniazid (HR: 0.95, p = 0.87) or amlodipine (HR: 0.43, p = 0.24). Gynecomastia resolved in 83.5% of cases following withdrawal of efavirenz with a median time to resolution of 3 months (IQR: 2-9). CONCLUSION: The incidence of gynecomastia among patients taking efavirenz-based ART was low with most cases developing early on during treatment. Most cases resolved completely after withdrawing efavirenz.

New-onset type 2 diabetes mellitus among patients receiving HIV care at Newlands Clinic, Harare, Zimbabwe: retrospective cohort analysis.

OBJECTIVE: To assess the incidence and associated factors of Type 2 Diabetes Mellitus (T2DM) among people living with HIV (PLHIV) in Zimbabwe. METHODS: We analysed data of all HIV-infected patients older than 16 years who attended Newlands Clinic between March 1, 2004 and April 29, 2015. The clinic considers patients whose random blood sugar is higher than 11.1 mmol/l and which is confirmed by a fasting blood sugar higher than 7.0 mmol/l to have T2DM. T2DM is also diagnosed in symptomatic patients who have a RBS >11.0 mmol/l. Risk factors for developing T2DM were identified using Cox proportional hazard models adjusted for confounding. Missing baseline BMI data were multiply imputed. Results are presented as adjusted hazard ratios (aHR) with 95% confidence intervals (95% CI). RESULTS: Data for 4,110 participants were included: 67.2% were women; median age was 37 (IQR: 31-43) years. Median baseline CD4 count was 197 (IQR: 95-337) cells/mm3 . The proportion of participants with hypertension at baseline was 15.5% (n=638). Over a median follow-up time of 4.7 (IQR: 2.1-7.2) years, 57 patients developed T2DM; the overall incidence rate was 2.8 (95% CI: 2.1-3.6) per 1000 person-years of follow-up. Exposure to PIs was associated with T2DM (HR: 1.80, 95% CI: 1.04-3.09). In the multivariable analysis, obesity (BMI>30 kg/m2 ) (aHR=2.26, 95% CI: 1.17-4.36), age >40 years (aHR=2.16, 95% CI: 1.22-3.83) and male gender, (aHR=2.13, 95% CI: 1.22-3.72) were independently associated with the risk of T2DM. HIV-related factors (baseline CD4 cell count and baseline WHO clinical stage) were not independent risk factors for developing T2DM. CONCLUSION: Although the incidence of T2DM in this HIV cohort was lower than that has been observed in others, our results show that risk factors for developing T2DM among HIV-infected people are similar to those of the general population. HIV-infected patients in sub-Saharan Africa need a comprehensive approach to care that includes better health services for prevention, early detection and treatment of chronic diseases especially among the elderly and obese.

Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa.

BACKGROUND: As antiretroviral therapy (ART) programs in sub-Saharan Africa mature, increasing numbers of persons with human immunodeficiency virus (HIV) infection will experience treatment failure, and require second- or third-line ART. Data on second-line failure and development of protease inhibitor (PI) resistance in sub-Saharan Africa are scarce. METHODS: HIV-1-infected adults were included if they received >180 days of PI-based second-line ART. We assessed risk factors for having a detectable viral load (VL, ≥400 cps/mL) using Cox models. If VL was ≥1000 cps/mL, genotyping was performed. RESULTS: Of 227 included participants, 14.6%, 15.2% and 11.1% had VLs ≥400 cps/mL at 12, 24, and 36 months, respectively. Risk factors for a detectable VL were as follows: exposure to nonstandard nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based (hazard ratio, 7.10; 95% confidence interval, 3.40-14.83; P < .001) or PI-based (7.59; 3.02-19.07; P = .001) first-line regimen compared with zidovudine/lamivudine/NNRTI, PI resistance at switch (6.69; 2.49-17.98; P < .001), and suboptimal adherence (3.05; 1.71-5.42; P = .025). Among participants with VLs ≥1000 cps/mL, 22 of 32 (69%) harbored drug resistance mutation(s), and 7 of 32 (22%) harbored PI resistance. CONCLUSIONS: Although VL suppression rates were high, PI resistance was detected in 22% of participants with VLs ≥1000 cps/mL. To ensure long-term ART success, intensified support for adherence, VL and drug resistance testing, and third-line drugs will be necessary.

Kaposi Sarcoma Risk in HIV-Infected Children and Adolescents on Combination Antiretroviral Therapy From Sub-Saharan Africa, Europe, and Asia.

BACKGROUND: The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. METHODS: We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS and the Collaboration of Observational HIV Epidemiological Research in Europe. We included HIV-infected children aged <16 years at cART initiation from 1996 onward. We used Cox models to calculate hazard ratios (HRs), adjusted for region and origin, sex, cART start year, age, and HIV/AIDS stage at cART initiation. RESULTS: We included 24 991 children from eastern Africa, southern Africa, Europe and Asia; 26 developed KS after starting cART. Incidence rates per 100 000 person-years (PYs) were 86 in eastern Africa (95% confidence interval [CI], 55-133), 11 in southern Africa (95% CI, 4-35), and 81 (95% CI, 26-252) in children of sub-Saharan African (SSA) origin in Europe. The KS incidence rates were 0/100 000 PYs in children of non-SSA origin in Europe (95% CI, 0-50) and in Asia (95% CI, 0-27). KS risk was lower in girls than in boys (adjusted HR [aHR], 0.3; 95% CI, .1-.9) and increased with age (10-15 vs 0-4 years; aHR, 3.4; 95% CI, 1.2-10.1) and advanced HIV/AIDS stage (CDC stage C vs A/B; aHR, 2.4; 95% CI, .8-7.3) at cART initiation. CONCLUSIONS: HIV-infected children from SSA but not those from other regions, have a high risk of developing KS after cART initiation. Early cART initiation in these children might reduce KS risk.

Body weight and blood pressure changes on dolutegravir-, efavirenz- or atazanavir-based antiretroviral therapy in Zimbabwe: a longitudinal study.

INTRODUCTION: Dolutegravir (DTG) is widely used for antiretroviral therapy (ART). We compared weight and blood pressure trends and examined the association between high blood pressure and weight gain among people living with HIV (PLHIV) switching to or starting DTG-based, efavirenz (EFV)-based and ritonavir-boosted atazanavir (ATV/r)-based ART in Zimbabwe. METHODS: PLHIV aged 18 years or older who started or switched to DTG, EFV or ATV/r-based ART between January 2004 and June 2022 at Newlands Clinic in Harare, Zimbabwe, were eligible. Weight was measured at all visits (Seca floor scales); blood pressure only at clinician-led visits (Omron M2 sphygmomanometer). We used Bayesian additive models to estimate trends in weight gain and the proportion with high blood pressure (systolic >140 mmHg or diastolic >90 mmHg) in the first 2 years after starting or switching the regimen. Finally, we examined whether trends in the proportion with high blood pressure were related to weight change. RESULTS: We analysed 99,969 weight and 35,449 blood pressure records from 9487 adults (DTG: 4593; EFV: 3599; ATV/r: 1295). At 24 months after starting or switching to DTG, estimated median weight gains were 4.54 kg (90% credibility interval 3.88-5.28 kg) in women and 3.71 kg (3.07-4.45 kg) in men, around twice that observed for ATV/r and over four-times the gain observed for EFV. Prevalence of high blood pressure among PLHIV receiving DTG-based ART increased from around 5% at baseline to over 20% at 24 months, with no change in PLHIV receiving EFV- or ATV/r-based ART. High blood pressure in PLHIV switching to DTG was associated with weight gain, with stronger increases in the proportion with high blood pressure for larger weight gains. CONCLUSIONS: Among PLHIV starting ART or switching to a new regimen, DTG-based ART was associated with larger weight gains and a substantial increase in the prevalence of high blood pressure. Routine weight and blood pressure measurement and interventions to lower blood pressure could benefit PLHIV on DTG-based ART. Further studies are needed to elucidate the mechanisms and reversibility of these changes after discontinuation of DTG.

Virologic outcomes on dolutegravir-, atazanavir-, or efavirenz-based ART in urban Zimbabwe: A longitudinal study.

There are few data from sub-Saharan Africa on the virological outcomes associated with second-line ART based on protease inhibitors or dolutegravir (DTG). We compared viral load (VL) suppression among people living with HIV (PLWH) on atazanavir (ATV/r)- or DTG-based second-line ART with PLWH on efavirenz (EFV)-based first-line ART. We analyzed data from the electronic medical records system of Newlands Clinic in Harare, Zimbabwe. We included individuals aged ≥12 years when commencing first-line EFV-based ART or switching to second-line DTG- or ATV/r-based ART with ≥24 weeks follow-up after start or switch. We computed suppression rates (HIV VL <50 copies/mL) at weeks 12, 24, 48, 72, and 96 and estimated the probability of VL suppression by treatment regimen, time since start/switch of ART, sex, age, and CD4 cell count (at start/switch) using logistic regression in a Bayesian framework. We included 7013 VL measurements of 1049 PLWH (61% female) initiating first-line ART and 1114 PLWH (58% female) switching to second-line ART. Among those switching, 872 (78.3%) were switched to ATV/r and 242 (21.7%) to DTG. VL suppression was lower in second-line ART than first-line ART, except at week 12, when those on DTG showed higher suppression than those on EFV (aOR 2.10, 95%-credible interval [CrI] 1.48-3.00) and ATV/r-based regimens (aOR 1.87, 95%-CrI 1.32-2.71). For follow-up times exceeding 24 weeks however, first-line participants demonstrated significantly higher VL suppression than second-line, with no evidence for a difference between DTG and ATV/r. Notably, from week 48 onward, VL suppression seemed to stabilize across all regimen groups, with an estimated 89.1% (95% CrI 86.9-90.9%) VL suppression in EFV, 74.5% (95%-CrI 68.0-80.7%) in DTG, and 72.9% (95%-CrI 69.5-76.1%) in ATV/r at week 48, showing little change for longer follow-up times. Virologic monitoring and adherence support remain essential even in the DTG era to prevent second-line treatment failure in settings with limited treatment options.

When to start antiretroviral therapy in children aged 2-5 years: a collaborative causal modelling analysis of cohort studies from southern Africa.

BACKGROUND: There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2-5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2-5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4 percentage (CD4%) <25%. METHODS AND FINDINGS: ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping. The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm(3) (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1-6.5) (no ART) to 2.1% (95% CI: 1.3%-3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%-3.5%) and 2.2% (95% CI: 1.4%-3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data. CONCLUSIONS: The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm(3) or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values. Please see later in the article for the Editors' Summary.

Assessing renal impairment in treatment-naïve adolescents living with HIV commencing antiretroviral therapy in Zimbabwe.

OBJECTIVE: People with HIV (PWH) are increasingly experiencing non-communicable complications, including renal impairment, which are associated with worse clinical outcomes. Limited information exists surrounding renal impairment in paediatric PWH, of which the majority live in sub-Saharan Africa, and further information is required to guide clinical practice. This study describes the prevalence of new or worsening renal impairment in adolescents commencing antiretroviral therapy (ART) in Zimbabwe and associated risk factors. DESIGN: Retrospective cohort study. METHODS: Data were collected between January 2010 to January 2019 from the medical records of adolescents aged 12-17 years initiating ART at an outpatient HIV clinic in Zimbabwe. Renal function (estimated glomerular filtration rate, eGFR) was calculated using the Full Age Spectrum formula. Proteinuria was defined as a single urine dipstick score of ≥1+. Potential predictors of renal impairment at follow-up were assessed by logistical regression. RESULTS: Two hundred and sixty-six adolescents were included in analysis. Baseline renal impairment (eGFR < 90 ml/min/1.73 m 2 ) and proteinuria were present in 13% and 7% of the cohort, respectively. After a median of 4.1 years (interquartile range: 1.9-6.9) following ART commencement, mean eGFR increased by 10 ml/min/1.73 m 2 ( P  < 0.01), and the prevalence of renal impairment decreased to 8% ( P  < 0.01). Baseline renal impairment predicted renal impairment at follow-up (odds ratio [OR] 8.98; 95% confidence interval [CI] 2.81-28.68; P  < 0.01). Proteinuria trended towards association with renal impairment at follow-up (OR 4.39; 95% CI 0.95-20.31; P  = 0.06). CONCLUSIONS: Renal impairment is common in adolescent ART-naïve PWH, and baseline renal impairment is associated with longstanding renal impairment, whereas baseline proteinuria trended towards an association with longstanding renal impairment.

Brief Report: Validation of the D:A:D Chronic Kidney Disease Risk Score Incorporating Proteinuria in People Living With HIV in Harare, Zimbabwe.

OBJECTIVE: We sought to validate the D:A:D risk score for chronic kidney disease (CKD) in people living with HIV in a cohort from Harare, Zimbabwe. In addition, we aimed to evaluate proteinuria as a predictive variable in the risk score model, being the first study to do so. DESIGN: Data from people living with HIV attending a clinic in Harare were evaluated. Those with a baseline estimated the glomerular filtration rate >60 mL/min/1.73 m 2 , and at least 2 subsequent estimated glomerular filtration rate measurements were included. A modified version of the D:A:D risk score model was applied to categorize participants as "low," "medium," and "high-risk" of progression to CKD. Potential predictors of renal impairment were assessed by logistic regression in univariate and multivariate models. Proteinuria was evaluated in a nested model using D:A:D risk categories. RESULTS: Two thousand seven hundred ninety-three participants were included. Forty participants (1.4% of the cohort) progressed to CKD during the median follow-up time of 4.2 years. Progression rates were 1%, 3%, and 12% in the low, medium, and high-risk groups, respectively. Proteinuria data were available for 2251 participants. The presence of proteinuria was strongly associated with progression to CKD [(OR 7.8, 95% CI: 3.9 to 15.7), and its inclusion in the risk score improved the discrimination of the model with the c-statistic increasing from 0.658 to 0.853]. CONCLUSION: A modified version of the D:A:D CKD risk score performed well in predicting CKD events among this sub-Saharan African cohort of people living with HIV. Inclusion of proteinuria into the risk score model significantly improved predictability.

Renal function and associated mortality risk in adults commencing HIV antiretroviral therapy in Zimbabwe.

BACKGROUND: People with HIV (PWH) in sub-Saharan Africa appear to have a higher incidence of renal disease than other global regions but data are limited. This renal impairment may be associated with an increased mortality risk. AIMS: To define the prevalence of renal disease and explore its association with mortality risk in a cohort from Zimbabwe commencing antiretroviral therapy (ART) for HIV infection. METHODS: A retrospective study of all patients aged at least 18 years, commenced on ART for HIV infection at the Newlands Clinic in Harare, Zimbabwe between January 2007 and September 2019 was conducted. Data were extracted from electronic medical records. Patients with no baseline creatinine measurement were excluded. Baseline characteristics were assessed as potential predictors for mortality by Cox proportional hazard regression. RESULTS: Three thousand and thirty-nine patients were eligible for inclusion. Most were female (62.1%), with a median age of 36 years (IQR 30-43). At baseline, 7.3% had an estimated glomerular filtration rate (eGFR) 90 ml/min per 1.73 m2 or less and 11.4% had proteinuria. Over a median follow-up period of 4.6 years (IQR 2.5-6.9), the mortality rate was 8.7%. One half of deaths (49.2%) occurred within the first year. In multivariable analysis, a baseline eGFR between 60 and 90 ml/min per 1.73 m2 [hazard ratio 2.22, 95% confidence interval (CI) 1.46-3.33, P < 0.001] and proteinuria (hazard ratio 2.10, 95% CI 1.35-3.27, P < 0.001) were associated with increased mortality risk. CONCLUSION: Baseline renal impairment was common. Both a reduced eGFR or proteinuria were independently associated with a doubling of mortality risk. These should serve as markers in the clinical setting of at-risk patients.

Cancer incidence among people living with HIV in Zimbabwe: A record linkage study.

BACKGROUND: People living with HIV (PLWH) are at increased risk of developing cancer. Cancer diagnoses are often incompletely captured at antiretroviral therapy (ART) clinics. AIM: To estimate the incidence and explore risk factors of cancer in a cohort of PLWH in Harare using probabilistic record linkage (PRL). METHODS: We conducted a retrospective cohort study that included PLWH aged ≥16 years starting ART between 2004 and 2017. We used PRL to match records from the Zimbabwe National Cancer Registry (ZNCR) with electronic medical records from an ART clinic in Harare to investigate the incidence of cancer among PLWH initiating ART. We matched records based on demographic data followed by manual clerical review. We followed PLWH up until first cancer diagnosis, death, loss to follow-up, or 31 December 2017, whichever came first. RESULTS: We included 3442 PLWH (64.9% female) with 19 346 person-years (PY) of follow-up. Median CD4 count at ART initiation was 169 cells/mm3 (interquartile range [IQR]: 82-275), median age was 36.6 years (IQR: 30.6-43.4). There were 66 incident cancer cases for an overall incidence rate of 341/100 000 PY (95% confidence interval [CI]: 268-434). Twenty-two of these cases were recorded in the ZNCR only. The most common cancers were cervical cancer (n = 16; 123/100 000 PY; 95% CI: 75-201), Kaposi sarcoma, and lymphoma (both n = 12; 62/100 000 PY; 95% CI: 35-109). Cancer incidence increased with age and decreased with higher CD4 cell counts at ART initiation. CONCLUSION: PRL was key to correct for cancer under-ascertainment in this cohort. The most common cancers were infection-related types, reinforcing the role of early HIV treatment, human papillomavirus vaccination, and cervical cancer screening for cancer prevention in this setting.

Cervical Cancer Screening Cascade for women living with HIV: a cohort study from Zimbabwe.

Countries with high HIV prevalence, predominantly in sub-Sahahran Africa, have the highest cervical cancer rates globally. HIV care cascades successfully facilitated the scale-up of antiretroviral therapy. A cascade approach could similarly succeed to scale-up cervical cancer screening, supporting WHO's goal to eliminate cervical cancer. We defined a Cervical Cancer Screening Cascade for women living with HIV (WLHIV), evaluating the continuum of cervical cancer screening integrated into an HIV clinic in Zimbabwe. We included WLHIV aged ≥18 years enrolled at Newlands Clinic in Harare from June 2012-2017 and followed them until June 2018. We used a cascade approach to evaluate the full continuum of secondary prevention from screening to treatment of pre-cancer and follow-up. We report percentages, median time to reach cascade stages, and cumulative incidence at two years with 95% confidence intervals (CI). We used univariable Cox proportional hazard regressions to calculate cause-specific hazard ratios with 95% CIs for factors associated with completing the cascade stages. We included 1624 WLHIV in the study. The cumulative incidence of cervical screening was 85.4% (95% CI 83.5-87.1) at two years. Among the 396 WLHIV who received screen-positive tests in the study, the cumulative incidence of treatment after a positive screening test was 79.5% (95% CI 75.1-83.2) at two years. The cumulative incidence of testing negative at re-screening after treatment was 36.1% (95% CI 31.2-40.7) at two years. Using a cascade approach to evaluate the full continuum of cervical cancer screening, we found less-than 80% of WLHIV received treatment after screen-positive tests and less-than 40% were screen-negative at follow-up. Interventions to improve linkage to treatment for screen-positive WLHIV and studies to understand the clinical significance of screen-positive tests at follow-up among WLHIV are needed. These gaps in the continuum of care must be addressed in order to prevent cervical cancer.

COVID-19 pandemic in Africa's island nations during the first 9 months: a descriptive study of variation in patterns of infection, severe disease, and response measures.

The geographic and economic characteristics unique to island nations create a different set of conditions for, and responses to, the spread of a pandemic compared with those of mainland countries. Here, we aimed to describe the initial period of the COVID-19 pandemic, along with the potential conditions and responses affecting variation in the burden of infections and severe disease burden, across the six island nations of the WHO's Africa region: Cabo Verde, Comoros, Madagascar, Mauritius, São Tomé e Príncipe and Seychelles. We analysed the publicly available COVID-19 data on confirmed cases and deaths from the beginning of the pandemic through 29 November 2020. To understand variation in the course of the pandemic in these nations, we explored differences in their economic statuses, healthcare expenditures and facilities, age and sex distributions, leading health risk factors, densities of the overall and urban populations and the main industries in these countries. We also reviewed the non-pharmaceutical response measures implemented nationally. We found that the burden of SARS-CoV-2 infection was reduced by strict early limitations on movement and biased towards nations where detection capacity was higher, while the burden of severe COVID-19 was skewed towards countries that invested less in healthcare and those that had older populations and greater prevalence of key underlying health risk factors. These findings highlight the need for Africa's island nations to invest more in healthcare and in local testing capacity to reduce the need for reliance on border closures that have dire consequences for their economies.

Metabolic syndrome among treatment-naïve people living with and without HIV in Zambia and Zimbabwe: a cross-sectional analysis.

INTRODUCTION: Chronic viral replication has been linked to an increased risk of cardiovascular and metabolic diseases in people living with HIV (PLWH), but few studies have evaluated this association in Southern Africa. We explored the determinants of metabolic syndrome (MetS) among treatment-naïve adults living with and without HIV in Southern Africa. METHODS: Treatment-naïve PLWH and people living without HIV (PLWOH) ≥30 years were consecutively enrolled from primary care clinics in Zambia and Zimbabwe. PLWOH were seronegative partners or persons presenting for HIV testing. We defined MetS as the presence of central obesity plus any two of the following: raised blood pressure, impaired fasting glucose, reduced high-density lipoprotein cholesterol and raised triglycerides, as defined by the International Diabetes Federation. We used logistic regression to determine factors associated with MetS. RESULTS: Between August 2019 and March 2022, we screened 1285 adults and enrolled 420 (47%) PLWH and 481 (53%) PLWOH. The median age was similar between PLWH and PLWOH (40 vs. 38 years, p < 0.24). In PLWH, the median CD4+ count was 228 cells/mm3 (IQR 108-412) and the viral load was 24,114 copies/ml (IQR 277-214,271). Central obesity was present in 365/523 (70%) females and 57/378 males (15%). MetS was diagnosed in 172/901 (19%, 95% confidence interval [CI] 17-22%), and prevalence was higher among females than males (27% vs. 9%). In multivariable analyses, HIV status was not associated with MetS (adjusted odds ratio [aOR] 1.05, 95% CI 0.74-1.51). Risk factors for MetS included age older than 50 years (aOR 2.31, 95% CI 1.49-3.59), female sex (aOR 3.47, 95% CI 2.15-5.60), highest income (aOR 2.19, 95% CI 1.39-3.44) and less than World Health Organization recommended weekly physical activity (aOR 3.35, 95% CI 1.41-7.96). CONCLUSIONS: We report a high prevalence of MetS and central obesity among females in urban Zambia and Zimbabwe. Lifestyle factors and older age appear to be the strongest predictors of MetS in our population, with no evident difference in MetS prevalence between treatment-naïve PLWH and PLWOH.

Effect of antiretroviral therapy care interruptions on mortality in children living with HIV.

OBJECTIVE: To evaluate the characteristics and outcomes of HIV-infected children that have care interruptions, during which the child's health status and use of medication is unknown. DESIGN: We included data on children initiating ART between 2004 and 2016 at less than 16 years old at 16 International Epidemiologic Databases to Evaluate AIDS Southern Africa cohorts. Children were classified as loss to follow up (LTFU) if they had not attended clinic for more than 180 days. Children had a care interruption if they were classified as LTFU, and subsequently returned to care. Children who died within 180 days of ART start were excluded. METHODS: The main outcome was all cause mortality. Two exposed groups were considered: those with a first care interruption within the first 6 months on ART, and those with a first care interruption after 6 months on ART. Adjusted hazard ratios were determined using a Cox regression model. RESULTS: Among 53 674 children included, 23 437 (44%) had a care interruption, of which 10 629 (20%) had a first care interruption within 6 months on ART and 12 808 (24%) had a first care interruption after 6 months on ART. Increased mortality was associated with a care interruption within 6 months on ART [adjusted hazard ratio (AHR) = 1.52, 95% CI 1.12-2.04] but not with a care interruption after 6 months on ART (AHR = 1.05, 95% CI 0.77-1.44). CONCLUSION: The findings suggest that strengthening retention of children in care in the early period after ART initiation is critical to improving paediatric ART outcomes.