Treatment outcomes in HIV infected patients older than 50 years attending an HIV clinic in Harare, Zimbabwe:A cohort study

There is a growing number of older people living with HIV (OPLHIV). While a significant proportion of this population are adults growing into old age with HIV, there are also new infections among OPLHIV. There is a lack of data describing the outcomes of OPLHIV who commenced antiretroviral therapy (ART) after the age of 50 years in sub-Saharan Africa. We conducted a cohort study of patients who enrolled in care at Newlands Clinic in Harare, Zimbabwe, at ages ≥50 years between February 2004 and March 2020. We examined demographic characteristics, attrition, viral suppression, immunological and clinical outcomes. Specifically, we described prevalent and incident HIV-related communicable and non-communicable comorbidities. We calculated frequencies, medians, interquartile ranges (IQR), and proportions; and used Cox proportional hazards models to identify risk factors associated with death. We included 420 (57% female) who commenced ART and were followed up for a median of 5.6 years (IQR 2.4-9.9). Most of the men were married (n = 152/179, 85%) whereas women were mostly widowed (n = 125/241, 51.9%). Forty per cent (n = 167) had WHO stage 3 or 4 conditions at ART baseline. Hypertension prevalence was 15% (n = 61) at baseline, and a further 27% (n = 112) had incident hypertension during follow-up. During follow-up, 300 (71%) were retained in care, 88 (21%) died, 17 (4%) were lost to follow-up, and 15 (4%) were transferred out. Of those in care, 283 (94%) had viral loads 1000 copies/ml. Seven patients (1.7%) were switched to second line ART during follow-up and none were switched to third-line. Higher baseline CD4 T-cell counts were protective against mortality (p = 0.001) while male sex (aHR: 2.29, 95%CI: 1.21-4.33), being unmarried (aHR: 2.06, 95%CI: 1.13-3.78), and being unemployed (aHR: 2.01, 95%CI: 1.2-3.37) were independent independent risk factors of mortality. There was high retention in care and virologic suppression in this cohort of OPLHIV. Hypertension was a common comorbidity. Being unmarried or unemployed were significant predictors of mortality highlighting the importance of sociologic factors among OPLHIV, while better immune competence at ART commencement was protective against mortality

"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 (PLWH) in a cohort from Harare, Zimbabwe. Additionally, we aimed to evaluate proteinuria as a predictive variable in the risk score model, being the first study to do so. DESIGN Data from PLWH attending a clinic in Harare was evaluated. Those with a baseline estimated glomerular filtration rate >60ml/min/1.73m2 and at least two subsequent eGFR measurements were included. A modified version of the D:A:D risk score model was applied to categorise 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 2793 participants were included. 40 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 was available for 2251 participants. Presence of proteinuria was strongly associated with progression to CKD [OR 7.8, 95% CI 3.9-15.7], 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

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

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

BACKGROUND People living with HIV (PLWHIV) 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 ≥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 3039 patients were eligible for inclusion. Most were female (62.1%), with a median age of 36 years (IQR 30 to 43). At baseline, 7.3% had an eGFR ≤90 mL/min/1.73m2 and 11.4% had proteinuria. Over a median follow-up period of 4.6 years (IQR 2.5 to 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/1.73m2 (HR 2.22, 95%CI 1.46 to 3.33, p < 0.001) and proteinuria (HR 2.10, 95%CI 1.35 to 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

Sexually transmitted infections, the silent partner in HIV-infected women in Zimbabwe

Background: Coinfection rates of HIV and sexually transmitted infections (STIs) are not widely reported in Zimbabwe and no local guidelines regarding the screening of STIs in people living with HIV exist.Objectives: This cross-sectional study was conducted to determine the prevalence and associated risk factors for STI coinfection in a cohort of HIV-infected women.Methods: Between January and June 2016, 385 HIV-infected women presenting for routine cervical cancer screening were tested for five STIs: Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV), Herpes Simplex Virus (HSV) type 2 and Treponema pallidum (TP). Socio-demographic characteristics and sexual history were recorded. Multiple logistic regression was used to identify factors associated with the diagnosis of non-viral STIs.Results: Two hundred and thirty-three participants (60.5%) had a confirmed positive result for at least one STI: HSV 2 prevalence 52.5%, TV 8.1%, CT 2.1%, NG 1.8% and TP 11.4%. Eighty seven per cent of the women were asymptomatic for any STI; 62.3% of women with a non-viral STI were asymptomatic. Women who had attended tertiary education were 90% less likely to have a non-viral STI (adjusted odds ratio [aOR]: 0.10, 95% confidence interval [CI]: 0.03–0.39, p &lt; 0.01). Having more than three lifetime sexual partners was a significant predictor for a nonviral STI diagnosis (aOR: 3.3, 95% CI: 1.5–7.2, p &lt; 0.01).Conclusion: A high prevalence of predominantly asymptomatic STIs is reported in a cohort of HIV-infected women. Syndromic management results in underdiagnosis of asymptomatic patients. More than three lifetime sexual partners and less formal education are risk factors for coinfection with non-viral STI. High-risk women should be screened using aetiological methods

Tenofovir, Lamivudine and Dolutegravir (TLD) among Rural Adolescents in Zimbabwe, a Cautionary Tale.

Tenofovir disoproxil fumarate, lamivudine and dolutegravir (TLD) as a safe and more effective single daily dose regimen is rolling out in Africa for people living with HIV. Although access to viral load (VL) testing is improving, patients may still be transitioned to TLD with virological failure and potential drug resistance. We reviewed annual VL test results of 390 children and adolescents who had enrolled in a community-based antiretroviral therapy programme in rural Zimbabwe between 2018 and 2019. VL testing was done by the near point of care Simplified Amplification-based Assays (Diagnostics for the Real World, Sunnyvale California) at Chidamoyo Christian Hospital. Rate of virological suppression (VS) on TLD (VL<1000 copies/ml) was assessed. Overall, 184 children and adolescents on TLD were enrolled in this study. The median (IQR) age was 15 (11-19) years, above half of the participants were female (57%). Prior to switching to TLD, rate of VS was 76% (139/184). After a median (IQR) duration of 6.9 (5.5-9.1) months on TLD, VS was observed in 95% (174/184) of the participants. Of the 10 participants with VL ≥1000 copies/ml on TLD, 90% (9/10) were failing on their previous regimens, 6/9 (67%) having been on boosted protease inhibitor- based regimens. A high rate (95%) of VS was observed among children and adolescents on TLD in rural Zimbabwe. TLD may address the problems of virologic failure and emergence of resistance in Africa. However, longer follow up might be needed to ascertain sustained VS in this vulnerable population

Sexually transmitted infections, the silent partner in HIV-infected women in Zimbabwe

Background: Coinfection rates of HIV and sexually transmitted infections (STIs) are not widely reported in Zimbabwe and no local guidelines regarding the screening of STIs in people living with HIV exist. Objectives: This cross-sectional study was conducted to determine the prevalence and associated risk factors for STI coinfection in a cohort of HIV-infected women. Methods: Between January and June 2016, 385 HIV-infected women presenting for routine cervical cancer screening were tested for five STIs: Neisseria gonorrhoeae (NG), Chlamydia trachomatis(CT), Trichomonas vaginalis (TV), Herpes Simplex Virus (HSV) type 2 and Treponema pallidum (TP). Socio-demographic characteristics and sexual history were recorded. Multiple logistic regression was used to identify factors associated with the diagnosis of non-viral STIs. Results: Two hundred and thirty-three participants (60.5%) had a confirmed positive result for at least one STI: HSV 2 prevalence 52.5%, TV 8.1%, CT 2.1%, NG 1.8% and TP 11.4%. Eighty-seven per cent of the women were asymptomatic for any STI; 62.3% of women with a non-viral STI were asymptomatic. Women who had attended tertiary education were 90% less likely to have a non-viral STI (adjusted odds ratio [aOR]: 0.10, 95% confidence interval [CI]: 0.03–0.39, p < 0.01). Having more than three lifetime sexual partners was a significant predictor for a non-viral STI diagnosis (aOR: 3.3, 95% CI: 1.5–7.2, p < 0.01). Conclusion: A high prevalence of predominantly asymptomatic STIs is reported in a cohort of HIV-infected women. Syndromic management results in underdiagnosis of asymptomatic patients. More than three lifetime sexual partners and less formal education are risk factors for coinfection with non-viral STI. High-risk women should be screened using aetiological methods

Patterns of detectable viraemia among children and adults with HIV infection taking antiretroviral therapy in Zimbabwe.

OBJECTIVE: To investigate the incidence and predictors of viraemia among individuals on antiretroviral therapy (ART) in Harare, Zimbabwe. METHODS: Children (0-19 years) and adults (>19 years) starting ART between 2013 and 2015 were followed for a median of 2.8 and 2.7 years, respectively. The incidence rates of virological failure (VF), low-level viraemia (LLV), and viral blips were assessed and the predictors of viraemia were determined using logistic and parametric survival regression analyses. RESULTS: A total of 630 individuals initiated ART, and 19.7% of children and 5.6% of adults did not achieve viral suppression by 12 months. Younger age and CD4 count ≤200 cells/mm3 at baseline were associated with not being virally suppressed at 12 months in adults. Among those who achieved viral suppression during the follow-up period, the incidence of VF was higher in children (4.0/100 person-years vs. 0.4/100 person-years in adults; p<0.001), as was the incidence of LLV (1.9/100 person-years vs. 0.3/100 person-years in adults; p=0.03). The incidence rate of blips was 10.9 per 100 person-years in children and 4.0 per 100 person-years in adults. CONCLUSIONS: Children are less likely to reach viral suppression and are at higher risk of viraemia while on ART than adults. The significance of LLV and blips needs further study

Clinic-based SAMBA-II vs centralized laboratory viral load assays among HIV-1 infected children, adolescents and young adults in rural Zimbabwe: A randomized controlled trial.

BACKGROUND In Zimbabwe, children, adolescents and young adults living with HIV (CALWH) who are on public health antiretroviral therapy (ART) have inadequate viral load (VL) suppression. We assessed whether a clinic-based VL monitoring could decrease 12-month virologic failure rates among these CALWH. METHODS The study was registered on ClinicalTrials.gov: NCT03986099. CALWH in care at Chidamoyo Christian Hospital (CCH) and 8 rural outreach sites (ROS) on long-term community-based ART were randomized (1:1) to 6 monthly VL monitoring by COBAS®Ampliprep®/Taqman48® HIV-1 at the provincial referral laboratory (PRL) as per standard of care (SOC) or by the clinic-based SAMBA II assay, Diagnostics for the Real World, at CCH. VL suppression, turn-around-time (TAT) for VL results, drug switching and drug resistance in second-line failure were assessed at 12 months. RESULTS Of 390 CALWH enrolled 347 (89%) completed 12 months follow-up. Median (IQR) age and ART duration were 14.1 (9.7-18.2) and 6.4 (3.7-7.9) years, respectively. Over half (57%) of the participants were female. At enrolment, 78 (20%) had VL ≥1,000 copies/ml and VL suppression of 80% was unchanged after 12 months, with no significant difference between the SOC (81%) and the clinic-based (80%) arms (p = 0.528). Median (IQR) months to confirmatory VL result at CCH vs PRL was 4.0 (2.1-4.4) vs 4.5 (3.5-6.3) respectively; p = 0.027 at 12 months. Drug switching was documented among 26/347 (7%) participants with no difference between the median (IQR) time to switch in SOC vs clinic-based arms (5.1 (3.9-10.0) months vs 4.4 (2.5-8.4) respectively; p = 0.569). Out of 24 confirmed second-line failures, only 4/19 (21%) had protease inhibitor resistance. CONCLUSION In rural Zimbabwe, the clinic-based SAMBA II assay was able to provide confirmatory VL results faster than the SOC VL assay at the PRL. However, this rapid TAT did not allow for a more efficient drug switch among these CALWH

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