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

The Impact of Herbal Drug Use on Adverse Drug Reaction Profiles of Patients on Antiretroviral Therapy in Zimbabwe

Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART). Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2%) of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%), Bidens pilosa (66.0%), Eucalyptus globulus (52.3%), Moringa oleifera (44.1%), Lippia javanica (36.3%), and Peltoforum africanum (34.3%). Two indigenous herbs, Musakavakadzi (OR = 0.25; 95% CI 0.076–0.828) and Peltoforum africanum (OR = 0.495; 95% CI 0.292–0.839) reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles

Risks to the community pharmacists and pharmacy personnel during COVID-19 pandemic:perspectives from a low-income country

Coronavirus disease 2019 (COVID-19) is an infectious disease that has become a global pandemic. COVID-19 is spreading in Africa, and Zimbabwe has not been spared. The cases in Zimbabwe are mainly from imported cases due to high volume of travellers from the COVID-19 hotspots. In Zimbabwe, local transmission is also anticipated due to inter- and intracity travelling. Frontline health workers are at risk of infection due to contact with infected people as they discharge their duties. In this setting, the risk to community pharmacists and pharmacy personnel is poorly understood and characterised. This paper looked at the risks of infection that are peculiar to community pharmacy personnel and suggested some recommendations to reduce the risk to COVID-19 infection

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 nonviral 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

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

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Determining the rate, nature and predictors of adverse drug reactions associated with the use of Highly Active Antiretroviral Therapy (HAART) in a resource limited setting (Zimbabwe)

Background: Dilemmas exist between balancing cost and toxicity of antiretroviral therapy (ART) in resource limited settings (RLS). Most pharmacovigilance programmes in RLS are unable to monitor adverse drug reactions (ADRs) due to inconsistent support systems. The study was carried out to implement a 3-step approach in identifying ADRs in patients on ART. The study was also designed to determine the rate nature and predictors of toxicities associated with ART in a RLS (Zimbabwe). Methods: The 3-step approach involved a pharmacist, physician and a drug regulatory agency (Medicines Control Authority of Zimbabwe, MCAZ) at each respective step. The pharmacist (investigator) was responsible for collecting data of suspected ADRs from the patient charts. The physician documented patient information in the patient charts, while the drug regulating body ascertained the causality of the suspected ADRs. The 3-step approach was used in ascertaining causality of cutaneous ADRs in 221 patients. To determine the rates and predictors of ADRs, 388 HIV positive adults stable on first line ART dispensed from Parirenyatwa Hospital, Harare, Zimbabwe were interviewed and their respective patient charts were consulted. Data analysis was carried out using the Statistical Analysis System (Version 9.2, Cary, North Carolina, USA). Three regression models, one multiple linear regression model and two logistic regression models were run to identify predictors of ADRs. Results: Of the 221 patient case report forms that were reviewed for causality assessment by the MCAZ, 39 patients had cutaneous drug eruptions. The rates of ADRs that were observed in the population included peripheral neuropathy (42%), skin rash (26%), lipodystrophy (3%), abdominal pain (8%), gastro-intestinal symptoms (7%) and headache (3%). Peripheral neuropathy and skin rash were mainly observed with stavudine (93%) and nevirapine (88%) based regimens respectively. Lipodystrophy occurred only in participants on stavudine based therapy. 161(58%) ADRs were grade 1 events (World Health Organization’s ADR grading system), 96(34%) were grade 2, 15(7%) were grade 3 and 1(0.3%) was grade 4. One patient on a nevirapine containing regimen had grade 4 Stevens - Johnson syndrome. In a logistic regression model, two indigenous herbal remedies were associated with the occurrence of ADRs in participants. Rates of toxicities were higher in the population receiving stavudine and nevirapine based therapies. Conclusion: Implementation of the 3-step approach in a RLS can an accurate technique in implementing pharmacovigilance programmes in RLS. The results of this study showed that 3 in every 4 patients initiated on first-line HAART in the government roll-out programme experienced a clinical adverse drug event

Profile of elderly patients receiving antiretroviral therapy at Newlands Clinic in 2020: A cross-sectional study

Background: People living with HIV (PLWH) face new challenges such as accelerated ageing and higher rates of comorbidities including cardiovascular, renal and metabolic diseases as they age. Objectives: To profile the demographic and clinical characteristics of elderly patients receiving HIV care at Newlands Clinic (NC), Harare, Zimbabwe, as of 01 October 2019. Methods: A cross-sectional analysis was conducted using clinic data. All patients who were 50 years and older on 01 October 2019 were enrolled. Descriptive statistics (medians, interquartile ranges [IQRs] and proportions) were used to describe patient demographic and clinical characteristics. Results: Out of 6543 patients undergoing care at NC, 1688 (25.8%) were older than 50 years. The median duration of antiretroviral therapy (ART) was 10.9 years (IQR: 7.1–13). Over 90% of all patients had an HIV viral load below 50 copies/mL. Women were more likely than men to be overweight and obese (32% and 25% vs. 18% and 7%, respectively). Hypertension (41.2%), arthritis (19.9%) and chronic kidney disease (11.6%) were common comorbidities differently distributed based on sex. The most common malignancy diagnosed in women was cervical intra-epithelial neoplasia (68% of cancer burden in women) and Kaposi sarcoma was the leading malignancy in men (41% of cancer burden in men). Nearly 20% of patients had at least two chronic non-communicable comorbidities and 5.6% had at least three. Conclusion: A high burden of comorbidities was observed amongst HIV-positive elderly patients receiving ART. Age-appropriate monitoring protocols must be developed to ensure optimum quality of care for elderly HIV-positive individuals

Group counselling for adherence support among young people failing first-line antiretroviral therapy in Zimbabwe.

Background Sub-optimal adherence to antiretroviral therapy (ART) is reportedly worse amongst young people living with HIV (YPLHIV). Group adherence counselling can be useful to improve adherence. Objectives We evaluated an enhanced adherence counselling group intervention (EACGI) amongst YPLHIV failing a non-nucleoside reverse transcriptase (NNRTI)-based first-line ART regimen. Method This was a retrospective cohort study using routinely collected data of YPLHIV failing NNRTI-based first-line ART. Patients with confirmed virological failure were referred for EACGI, a 12-week curriculum of weekly, 1.5-h sessions accommodating 8-15 people per group. It aimed to facilitate readiness to switch to second-line ART and improve adherence through a mental health intervention. Viral loads of HIV were measured pre-EACGI; at baseline; 3, 6 and 12 months post switch. Results Fifty-seven patients aged 13-25 years were invited to EACGI and followed for up to 48 weeks. Thirty-three (58%) patients attended at least four sessions, whilst 24 (42%) attended none. Amongst those who attended none, two (8%) were transferred out, three (13%) were lost to follow-up and two (8%) had died by week 48 of follow-up, whilst all who attended were still in care. By week 48, amongst patients still in care, 29%, 44% and 67% of those who attended no sessions, 4-9 and 10-12 sessions, respectively, had viral loads of < 50 copies/mL. Conclusion An EACGI is a promising intervention for YPLHIV failing ART prior to treatment switch, leading to improved adherence. This study's findings support the need for further enquiry into rigorous, evidence-based multilevel adherence interventions that are acceptable and effective for YPLHIV