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AbstractIntroductionThe success of HIV treatment programmes globally has resulted in children with perinatally acquired HIV reaching adolescence in large numbers. The number of adolescents living with HIV is growing further due to persisting high HIV incidence rates among adolescents in low‐ and middle‐income settings, particularly in sub‐Saharan Africa. Although expanding access to HIV viral load monitoring is necessary to achieve the 90‐90‐90 targets across the HIV care continuum, implementation is incomplete. We discuss the rationale for prioritizing viral load monitoring among adolescents and the associated challenges.DiscussionAdolescents with HIV are a complex group to treat successfully due to extensive exposure to antiretroviral therapy for those with perinatally acquired HIV and the challenges in sustained medication adherence in this age group. Given the high risk of treatment failure among adolescents and the limited drug regimens available in limited resource settings, HIV viral load monitoring in adolescents could prevent unnecessary and costly switches to second‐line therapy in virologically suppressed adolescents. Because adolescents living with HIV may be heavily treatment experienced, have suboptimal treatment adherence, or may be on second or even third‐line therapy, viral load testing would allow clinicians to make informed decisions about increased counselling and support for adolescents together with the need to maintain or switch therapeutic regimens.ConclusionsGiven scarce resources, prioritization of viral load testing among groups with a high risk of virological failure may be required. Adolescents have disproportionately high rates of virological failure, and targeting this age group for viral load monitoring may provide valuable lessons to inform broader scale‐up.

Rising concerns around antimicrobial resistance (AMR) have led to a renewed push to rationalise antibiotic prescribing in low- and middle-income countries (LMICs). There is increasing unease in conceptualising antibiotic use as individuals behaving '(ir)rationally' and recognition that rising use is emergent of and contributing to wider economic and political challenges. But in between these individual and societal 'drivers' of antibiotic use is an everyday articulation of care through these substances, written-in to the scripts, delivery chains and pedagogics of global healthcare. This article focuses on this everyday 'architecture' that over time and across spaces has knitted-in antibiotics and rhetorics of control that inform current responses to AMR. Based on historically informed ethnographic research in Zimbabwe, we examine points of continuity and change between 20th Century rational drug use (RDU) discourses and contemporary socio-political formations around AMR and antimicrobial stewardship (AMS), paying particular attention to their co-evolution with the process of pharmaceuticalisation. We illustrate how the framework and techniques of RDU were embedded within programmes to increase access to essential medicines and as such complemented the building of one of Africa's strongest postcolonial health systems in Zimbabwe. Whilst 20th Century RDU was focused on securing the health and safety of patients and affordability for systems, AMS programmes aim to secure medicines. Continuous through both RDU and AMS programmes is the persistent rhetoric of 'irrational use'. Health workers in Harare, attuned to the values and language of these programmes, enact in their everyday practice an architecture in which antibiotics have been designed-in. This research illustrates the struggle to optimise antibiotic use within current framings for action. We propose a reconfiguring of the architecture of global health such that frontline prescribers are able to provide 'good' care without necessarily turning to antibiotics. To design-out antibiotic reliance would require attention beyond '(ir)rationality', to the redrafting of blueprints that inscribe practice.

IntroductionRecent years have seen an increasing recognition of the need to improve access and retention in care for people living with HIV/AIDS. This review aims to quantify patients along the continuum of care in sub‐Saharan Africa and review possible interventions.MethodsWe defined the different steps making up the care pathway and quantified losses at each step between acquisition of HIV infection and retention in care on antiretroviral therapy (ART). We conducted a systematic review of data from studies conducted in sub‐Saharan Africa and published between 2000 and June 2011 for four of these steps and performed a meta‐analysis when indicated; existing data syntheses were used for the remaining two steps.ResultsThe World Health Organization estimates that only 39% of HIV‐positive individuals are aware of their status. Among patients who know their HIV‐positive status, just 57% (95% CI, 48 to 66%) completed assessment of ART eligibility. Of eight studies using an ART eligibility threshold of≤200 cells/µL, 41% of patients (95% CI, 27% to 55%) were eligible for treatment, while of six studies using an ART eligibility threshold of≤350 cells/µL, 57% of patients (95% CI, 50 to 63%) were eligible. Of those not yet eligible for ART, the median proportion remaining in pre‐ART care was 45%. Of eligible individuals, just 66% (95% CI, 58 to 73%) started ART and the proportion remaining on therapy after three years has previously been estimated as 65%. However, recent studies highlight that this is not a simple linear pathway, as patients cycle in and out of care. Published studies of interventions have mainly focused on reducing losses at HIV testing and during ART care, whereas few have addressed linkage and retention during the pre‐ART period.ConclusionsLosses occur throughout the care pathway, especially prior to ART initiation, and for some patients this is a transient event, as they may re‐engage in care at a later time. However, data regarding interventions to address this issue are scarce. Research is urgently needed to identify effective solutions so that a far greater proportion of infected individuals can benefit from long‐term ART.

IntroductionSeveral approaches have been taken to reduce pre‐antiretroviral therapy (ART) losses between HIV testing and ART initiation in low‐ and middle‐income countries, but a systematic assessment of the evidence has not yet been undertaken. The aim of this systematic review is to assess the potential for interventions to improve or facilitate linkage to or retention in pre‐ART care and initiation of ART in low‐ and middle‐income settings.MethodsAn electronic search was conducted on Medline, Embase, Global Health, Web of Science and conference databases to identify studies describing interventions aimed at improving linkage to or retention in pre‐ART care or initiation of ART. Additional searches were conducted to identify on‐going trials on this topic, and experts in the field were contacted. An assessment of the risk of bias was conducted. Interventions were categorized according to key domains in the existing literature.ResultsA total of 11,129 potentially relevant citations were identified, of which 24 were eligible for inclusion, with the majority (n=21) from sub‐Saharan Africa. In addition, 15 on‐going trials were identified. The most common interventions described under key domains included: health system interventions (i.e. integration in the setting of antenatal care); patient convenience and accessibility (i.e. point‐of‐care CD4 count (POC) testing with immediate results, home‐based ART initiation); behaviour interventions and peer support (i.e. improved communication, patient referral and education) and incentives (i.e. food support). Several interventions showed favourable outcomes: integration of care and peer supporters increased enrolment into HIV care, medical incentives increased pre‐ART retention, POC CD4 testing and food incentives increased completion of ART eligibility screening and ART initiation. Most studies focused on the general adult patient population or pregnant women. The majority of published studies were observational cohort studies, subject to an unclear risk of bias.ConclusionsFindings suggest that streamlining services to minimize patient visits, providing adequate medical and peer support, and providing incentives may decrease attrition, but the quality of the current evidence base is low. Few studies have investigated combined interventions, or assessed the impact of interventions across the HIV cascade. Results from on‐going trials investigating POC CD4 count testing, patient navigation, rapid ART initiation and mobile phone technology may fill the quality of evidence gap. Further high‐quality studies on key population groups are required, with interventions informed by previously reported barriers to care.

IntroductionIn recent years children and adolescents have emerged as a priority for HIV prevention and care services. We conducted a systematic review to investigate the acceptability, yield and prevalence of HIV testing and counselling (HTC) strategies in children and adolescents (5 to 19 years) in sub‐Saharan Africa.MethodsAn electronic search was conducted in MEDLINE, EMBASE, Global Health and conference abstract databases. Studies reporting on HTC acceptability, yield and prevalence and published between January 2004 and September 2014 were included. Pooled proportions for these three outcomes were estimated using a random effects model. A quality assessment was conducted on included studies.Results and discussionA total of 16,380 potential citations were identified, of which 21 studies (23 entries) were included. Most studies were conducted in Kenya (n=5) and Uganda (n=5) and judged to provide moderate (n=15) to low quality (n=7) evidence, with data not disaggregated by age. Seven studies reported on provider‐initiated testing and counselling (PITC), with the remainder reporting on family‐centred (n=5), home‐based (n=5), outreach (n=5) and school‐linked HTC among primary schoolchildren (n=1). PITC among inpatients had the highest acceptability (86.3%; 95% confidence interval [CI]: 65.5 to 100%), yield (12.2%; 95% CI: 6.1 to 18.3%) and prevalence (15.4%; 95% CI: 5.0 to 25.7%). Family‐centred HTC had lower acceptance compared to home‐based HTC (51.7%; 95% CI: 10.4 to 92.9% vs. 84.9%; 95% CI: 74.4 to 95.4%) yet higher prevalence (8.4%; 95% CI: 3.4 to 13.5% vs. 3.0%; 95% CI: 1.0 to 4.9%). School‐linked HTC showed poor acceptance and low prevalence.ConclusionsWhile PITC may have high test acceptability priority should be given to evaluating strategies beyond healthcare settings (e.g. home‐based HTC among families) to identify individuals earlier in their disease progression. Data on linkage to care and cost‐effectiveness of HTC strategies are needed to strengthen policies.

IntroductionRoutine viral load (VL) monitoring is utilized to assess antiretroviral therapy (ART) adherence and virologic failure, and it is currently scaled‐up in many resource‐constrained settings. The first routine VL is recommended as late as six months after ART initiation for early detection of sub‐optimal adherence. We aimed to assess the optimal timing of first VL measurement after initiation of ART.MethodsThis was a retrospective, cohort analysis of routine monitoring data of adults enrolled at three primary care clinics in Khayelitsha, Cape Town, between January 2002 and March 2009. Primary outcomes were virologic failure and switch to second‐line ART comparing patients in whom first VL done was at three months (VL3M) and six months (VL6M) after ART initiation. Adjusted hazard ratios (aHR) were estimated using Cox proportional hazard models.ResultsIn total, 6264 patients were included for the time to virologic failure and 6269 for the time to switch to second‐line ART analysis. Patients in the VL3M group had a 22% risk reduction of virologic failure (aHR 0.78, 95% CI 0.64–0.95; p=0.016) and a 27% risk reduction of switch to second‐line ART (aHR 0.73, 95% CI 0.58–0.92; p=0.008) when compared to patients in the VL6M group. For each additional month of delay of the first VL measurement (up to nine months), the risk of virologic failure increased by 9% (aHR 1.09, 95% CI 1.02–1.15; p=0.008) and switch to second‐line ART by 13% (aHR 1.13, 95% CI 1.05–1.21; p<0.001).ConclusionsA first VL at three months rather than six months with targeted adherence interventions for patients with high VL may improve long‐term virologic suppression and reduce switches to costly second‐line ART. ART programmes should consider the first VL measurement at three months after ART initiation.

AbstractIntroduction: Rapid diagnostic tests (RDT) for HIV infection have high sensitivity and specificity, but in the setting of longstanding antiretroviral therapy (ART), can give false results that can lead to misinterpretation, confusion and inadequate management. The objective of this study was to evaluate the proportion of falsely negative results of a RDT performed on oral fluid in HIV‐infected children on longstanding ART.Methods: One hundred and twenty‐nine children with known HIV infection and receiving ART were recruited from the HIV Clinic at the Harare Central Hospital, Zimbabwe. HIV testing was performed on oral fluid and on finger‐stick blood.Results and Discussion: Children included in the study had a median age of 12 years (IQR 10–14) and 67 (51.9%) were female. Median age at HIV diagnosis was 5 years (IQR 3–6) and the median time on ART was 6.3 years (IQR 4.3–8.1). The oral fluid test was negative in 11 (8.5%) patients and indeterminate in 2 (1.6%). Finger‐stick blood test was negative in 1 patient. Patients with a negative oral fluid test had a higher CD4 cell count (967 vs. 723 cells/mm3, p = 0.016) and a longer time on ART (8.5 vs. 6 years, p = 0.016).Conclusions: This study found that a substantial proportion of false‐negative HIV test results in children on longstanding ART when using an oral fluid test. This could lead to misinterpretation of HIV test results and in the false perception of cure or delayed diagnosis.

IntroductionDespite significant progress in improving access to antiretroviral therapy over the past decade, substantial numbers of people living with HIV (PLHIV) in all regions continue to experience severe illness and require hospitalization. We undertook a global review assessing the proportion of hospitalizations and in‐hospital deaths because of tuberculosis (TB) in PLHIV.MethodsSeven databases were searched to identify studies reporting causes of hospitalizations among PLHIV from 1 January 2007 to 31 January 2015 irrespective of age, geographical region or language. The proportion of hospitalizations and in‐hospital mortality attributable to TB was estimated using random effects meta‐analysis.ResultsFrom an initial screen of 9049 records, 66 studies were identified, providing data on 35,845 adults and 2792 children across 42 countries. Overall, 17.7% (95% CI 16.0 to 20.2%) of all adult hospitalizations were because of TB, making it the leading cause of hospitalization overall; the proportion of adult hospitalizations because of TB exceeded 10% in all regions except the European region. Of all paediatric hospitalizations, 10.8% (95% CI 7.6 to 13.9%) were because of TB. There was insufficient data among children for analysis by region. In‐hospital mortality attributable to TB was 24.9% (95% CI 19.0 to 30.8%) among adults and 30.1% (95% CI 11.2 to 48.9%) among children.DiscussionTB remains a leading cause of hospitalization and in‐hospital death among adults and children living with HIV worldwide.

BACKGROUND: There is a substantial burden of HIV infection among older children in sub-Saharan Africa, the majority of whom are diagnosed after presentation with advanced disease. We investigated the provision and uptake of provider-initiated HIV testing and counselling (PITC) among children in primary health care facilities, and explored health care worker (HCW) perspectives on providing HIV testing to children. METHODS AND FINDINGS: Children aged 6 to 15 y attending six primary care clinics in Harare, Zimbabwe, were offered PITC, with guardian consent and child assent. The reasons why testing did not occur in eligible children were recorded, and factors associated with HCWs offering and children/guardians refusing HIV testing were investigated using multivariable logistic regression. Semi-structured interviews were conducted with clinic nurses and counsellors to explore these factors. Among 2,831 eligible children, 2,151 (76%) were offered PITC, of whom 1,534 (54.2%) consented to HIV testing. The main reasons HCWs gave for not offering PITC were the perceived unsuitability of the accompanying guardian to provide consent for HIV testing on behalf of the child and lack of availability of staff or HIV testing kits. Children who were asymptomatic, older, or attending with a male or a younger guardian had significantly lower odds of being offered HIV testing. Male guardians were less likely to consent to their child being tested. 82 (5.3%) children tested HIV-positive, with 95% linking to care. Of the 940 guardians who tested with the child, 186 (19.8%) were HIV-positive. CONCLUSIONS: The HIV prevalence among children tested was high, highlighting the need for PITC. For PITC to be successfully implemented, clear legislation about consent and guardianship needs to be developed, and structural issues addressed. HCWs require training on counselling children and guardians, particularly male guardians, who are less likely to engage with health care services. Increased awareness of the risk of HIV infection in asymptomatic older children is needed.

AbstractIntroduction: Decentralized HIV care for adults does not appear to compromise clinical outcomes. HIV care for children poses additional clinical and social complexities. We conducted a prospective cohort study to investigate clinical outcomes in children aged 6–15 years who registered for HIV care at seven primary healthcare clinics (PHCs) in Harare, Zimbabwe.Methods: Participants were recruited between January 2013 and December 2014 and followed for 18 months. Rates of and reasons for mortality, hospitalization and unscheduled PHC attendances were ascertained. Cox proportional modelling was used to determine the hazard of death, unscheduled attendances and hospitalization.Results: We recruited 385 participants, median age 11 years (IQR: 9–13) and 52% were female. The median CD4 count was 375 cells/mm3 (IQR: 215–599) and 77% commenced ART over the study period, with 64% of those who had viral load measured achieving an HIV viral load <400 copies/ml. At 18 months, 4% of those who started ART vs. 24% of those who remained ART‐naïve were lost‐to‐follow‐up (p < 0.001). Hospitalization and mortality rates were low (8.14/100 person‐years (pyrs) and 2.86/100 pyrs, respectively). There was a high rate of unscheduled PHC attendances (34.94/100 pyrs), but only 7% resulted in hospitalization. Respiratory disease was the major cause of hospitalization, unscheduled attendances and death. CD4 count <350cells/mm3 was a risk factor for hospitalization (aHR 3.6 (95%CI 1.6–8.2)).Conclusions: Despite only 64% of participants achieving virological suppression, clinical outcomes were good and high rates of retention in care were observed. This demonstrates that in an era moving towards differentiated care in addition to implementation of universal treatment, decentralized HIV care for children is achievable. Interventions to improve adherence in this age‐group are urgently needed.

Background There is a substantial burden of HIV infection among older children in sub-Saharan Africa, the majority of whom are diagnosed after presentation with advanced disease. We investigated the provision and uptake of provider-initiated HIV testing and counselling (PITC) among children in primary health care facilities, and explored health care worker (HCW) perspectives on providing HIV testing to children. Methods and Findings Children aged 6 to 15 y attending six primary care clinics in Harare, Zimbabwe, were offered PITC, with guardian consent and child assent. The reasons why testing did not occur in eligible children were recorded, and factors associated with HCWs offering and children/guardians refusing HIV testing were investigated using multivariable logistic regression. Semi-structured interviews were conducted with clinic nurses and counsellors to explore these factors. Among 2,831 eligible children, 2,151 (76%) were offered PITC, of whom 1,534 (54.2%) consented to HIV testing. The main reasons HCWs gave for not offering PITC were the perceived unsuitability of the accompanying guardian to provide consent for HIV testing on behalf of the child and lack of availability of staff or HIV testing kits. Children who were asymptomatic, older, or attending with a male or a younger guardian had significantly lower odds of being offered HIV testing. Male guardians were less likely to consent to their child being tested. 82 (5.3%) children tested HIV-positive, with 95% linking to care. Of the 940 guardians who tested with the child, 186 (19.8%) were HIV-positive. Conclusions The HIV prevalence among children tested was high, highlighting the need for PITC. For PITC to be successfully implemented, clear legislation about consent and guardianship needs to be developed, and structural issues addressed. HCWs require training on counselling children and guardians, particularly male guardians, who are less likely to engage with health care services. Increased awareness of the risk of HIV infection in asymptomatic older children is needed.

AbstractIntroduction: Globally, increasing numbers of HIV‐infected children are reaching adolescence due to antiretroviral therapy (ART). We investigated rates of loss‐to‐follow‐up (LTFU) from HIV care services among children as they transition from childhood through adolescence.Methods: Individuals aged 5–19 years initiated on ART in a public‐sector HIV clinic in Bulawayo, Zimbabwe, between 2005 and 2009 were included in a retrospective cohort study. Participants were categorized into narrow age‐bands namely: 5–9 (children), 10–14 (young adolescents) and 15–19 (older adolescents). The effect of age at ART initiation, current age (using a time‐updated Lexis expansion) and transitioning from one age group to the next on LTFU was estimated using Poisson regression.Results: Of 2273 participants, 1013, 875 and 385 initiated ART aged 5–9, 10–14 and 15–19 years, respectively. Unlike those starting ART as children, individuals starting ART as young adolescents had higher LTFU rates after moving to the older adolescent age‐band (Adjusted rate ratio (ARR) 1.54; 95% CI: 0.94–2.55) and similarly, older adolescents had higher LTFU rates after transitioning to being young adults (ARR 1.79; 95% CI: 1.05–3.07). In older adolescents, the LTFU rate among those who started ART in that age‐band was higher compared to the rate among those starting ART at a younger age (ARR = 1.70; 95% CI: 1.05, 2.77). This however did not hold true for other age‐groups.Conclusions: Adolescents had higher rates of LTFU compared to other age‐groups, with older adolescents at particularly high risk in all analyses. Age‐updated analyses that examine movement across narrow age‐bands are paramount in understanding how developmental heterogeneity in children affects HIV outcomes.

AbstractIntroductionIn sub‐Saharan Africa, less than half of young people know their HIV status. HIV self‐testing (HIVST) is a testing strategy with the potential to offer privacy and autonomy. We aimed to understand the uptake and acceptability of different HIV testing options for youth in Harare, Zimbabwe.MethodsThis study was nested within a cluster randomized trial of a youth‐friendly community‐based integrated HIV and sexual and reproductive health intervention for youth aged 16–24 years. Three HIV testing options were offered: (1) provider‐delivered testing; (2) HIVST on site in a private booth without a provider present; and (3) provision of a test kit to test off site. Descriptive statistics and proportions were used to investigate the uptake of HIV testing in a client sample. A focus group discussion (FGD) with intervention providers alongside in‐depth interviews, paired interviews and FGDs with a selected sample of youth clients explored uptake and acceptability of the different HIV testing strategies. Thematic analysis was used to analyse the qualitative data.ResultsBetween April and June 2019, 951 eligible clients were tested for HIV: 898 (94.4%) chose option 1, 30 (3.25%) chose option 2 and 23 (2.4%) chose option 3. Option 1 clients cited their trust in the service and a desire for immediate counselling, support and guidance from trusted providers as the reasons for their choice. Young people were not confident in their expertise to conduct HIVST. Concerns about limited privacy, confidentiality and lack of support in the event of an HIV‐positive result were barriers for off‐site HIVST.ConclusionsIn the context of supportive, trusted and youth‐friendly providers, youth clients overwhelmingly preferred provider‐delivered HIV testing over client‐initiated HIVST or HIVST off site. This highlights the importance of listening to youth to improve engagement in testing. While young people want autonomy in choosing when, where and how to test, they do not want to necessarily test on their own. They desire quality in‐person counselling, guidance and support, alongside privacy and confidentiality. To increase the appeal of HIVST for youth, greater provision of access to private spaces is required, and accessible pre‐ and post‐test counselling and support may improve uptake.

AbstractThe COVID‐19 pandemic has had serious impacts on economic, social, and health systems, and fragile public health systems have become overburdened in many countries, exacerbating existing service delivery challenges. This study describes the impact of the COVID‐19 pandemic on family planning services within a community‐based integrated HIV and sexual and reproductive health intervention for youth aged 16–24 years being trialled in Zimbabwe (CHIEDZA). It examines the experiences of health providers and clients in relation to how the first year of the pandemic affected access to and use of contraceptives.