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Introduction: Definitions of retention-in-care in Prevention of Mother-to-Child Transmission of HIV (PMTCT) vary substantially between studies and programmes. Some definitions are based on visits missed/made, others on a minimum total number of visits, or attendance at a final clinic visit at a specific time. An agreed definition could contribute to developing evidence-based interventions for improving retention-in-care. In this paper, we estimated retention-in-care rates according to different definitions, and we quantified and visualized the degree of agreement between definitions. Methods: We calculated retention in care rates using nine definitions in the six INSPIRE PMTCT intervention studies, conducted in three sub-Saharan African countries between 2013 and 2017. With data from one of the studies (E4E), we estimated the agreement between definitions using Gwet's agreement coefficient (AC1) and concordance. We calculated positive predictive values (PPV) and negative predictive values (NPV) for all definitions considering successively each definition as the reference standard. Finally, we used a Multiple Correspondence Analysis (MCA) to examine clustering of the way different definitions handle retention-in-care. Results: Retention-in-care rates among 5107 women ranged from 30% to 76% in the complete dataset with Gwet's AC1 being 0.56 [0.53; 0.59] indicating a moderate agreement between all definitions together. Two pairs of definitions with high inner concordance and agreement had either very high PPV or very high NPV, and appeared distinct from the other five definitions on the MCA figures. These pairs of definitions were also the ones resulting in the lowest and highest estimates of retention-in-care. The simplest definition, that only required a final clinic visit to classify women as retained in care, and classified 55% of women as retained in care, had a PPV ranging from 0.7 to 1 and a NPV ranging from 0.69 to 0.98 when excluding the two pairs afore-mentioned; it resulted in a moderate to substantial agreement and a 70% to 90% concordance with all other definitions. Conclusions: Our study highlights the variability of definitions in estimating retention-in-care. Some definitions are very stringent which may be required in some instances. A simple indicator such as attendance at a single time point may be sufficient for programme planning and evaluation. Keywords: HIV care continuum; retention; Africa; women; PMTCT; outcome assessment, 1 | INTRODUCTION Lifelong antiretroviral treatment (ART) for mothers living with HIV is critical for the Prevention of Mother-to-Child Transmission of HIV (PMTCT) [1]. ART benefits women's own health and [...]

Introduction: The World Health Organization (WHO) recommends a CD4 cell count before starting antiretroviral therapy (ART) to detect advanced HIV disease, and routine viral load (VL) testing following ART initiation to detect treatment failure. Donor support for CD4 testing has declined to prioritize access to VL monitoring. We examined trends in CD4 and VL testing among adults ([greater than or equal to]15 years of age) starting ART in Southern Africa. Methods: We analysed data from 14 HIV treatment programmes in Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in 2005 to 2018. We examined the frequency of CD4 and VL testing, the percentage of adults with CD4 or VL tests, and among those having a test, the percentage starting ART with advanced HIV disease (CD4 count 1000 HIV-RNA copies/mL) after ART initiation. We used mixed effect logistic regression to assess time trends adjusted for age and sex. Results: Among 502,456 adults, the percentage with CD4 testing at ART initiation decreased from a high of 78.1% in 2008 to a low of 38.0% in 2017; the probability declined by 14% each year (odds ratio (OR) 0.86; 95% CI 0.86 to 0.86). Frequency of CD4 testing also declined. The percentage starting ART with advanced HIV disease declined from 83.3% in 2005 to 23.5% in 2018; each year the probability declined by 20% (OR 0.80; 95% CI 0.80 to 0.81). VL testing after starting ART varied; 61.0% of adults in South Africa and 10.7% in Malawi were tested, but fewer than 2% were tested in the other four countries. The probability of VL testing after ART start increased only modestly each year (OR 1.06; 95% CI 1.05 to 1.06). The percentage with unsuppressed VL was 8.6%. There was no evidence of a decrease in unsuppressed VL over time (OR 1.00; 95% CI 0.99 to 1.01). Conclusions: CD4 cell counting declined over time, including testing at the start of ART, despite the fact that many patients still initiated ART with advanced HIV disease. Without CD4 testing and expanded VL testing many patients with advanced HIV disease and treatment failure may go undetected, threatening the effectiveness of ART in sub-Saharan Africa. Keywords: CD4 lymphocyte count; viral load; Africa; Southern; antiretroviral therapy; highly active; Cohort studies; HIV infections, 1 | INTRODUCTION The World Health Organization (WHO) has recommended immediate initiation of antiretroviral therapy (ART) for all people living with HIV since 2015, regardless of CD4 cell count or [...]

Introduction: As adolescents and young people living with HIV (AYLH) age, they face a 'transition cascade,' a series of steps associated with transitions in their care as they become responsible for their own healthcare. In high-income countries, this usually includes transfer from predominantly paediatric/adolescent to adult clinics. In sub-Saharan Africa, paediatric HIV care is mostly provided in decentralized, non-specialist primary care clinics, where 'transition' may not necessarily include transfer of care but entails becoming more autonomous for one's HIV care. Using different age thresholds as proxies for when 'transition' to autonomy might occur, we evaluated pre- and post-transition outcomes among AYLH. Methods: We included AYLH aged Results: A total of 5516 AYLH from 16 sites were included at 'transition' age 16 (transition-16y), 3864 at 18 (transition-18y), 1463 at 20 (transition-20y) and 440 at 22 years (transition-22y). At transition-18y in the 12 months pre- and post-transition, 83% versus 74% of AYLH had no gap in care (difference 9.3 (95% confidence interval (CI) 7.8 to 10.9)); while 65% versus 62% were virally suppressed (difference 2.7 (-1.0 to 6.5%)). The strongest predictor of being retained post-transition was having no gap in the preceding year, across all transition age thresholds (transition-16y adjusted risk ratio (aRR) 1.72; 95% CI (1.60 to 1.86); transition-18y: aRR 1.76 (1.61 to 1.92); transition-20y: aRR 1.75 (1.53 to 2.01); transition-22y: aRR 1.47; (1.21 to 1.78)). Conclusions: AYLH with gaps in care need targeted support to prevent non-retention as they take on greater responsibility for their healthcare. Interventions to increase virologic suppression rates are necessary for all AYLH ageing to adulthood. Keywords: HIV; adolescents; youth; healthcare transition; retention; viral suppression; cascade of care, 1 | INTRODUCTION There is a growing cohort of adolescents and young adults living with HIV (AYLH), largely due to the increasing number of children with perinatally acquired HIV surviving [...]

Introduction: Although the use of antiretroviral therapy (ART) reduces HIV-associated tuberculosis (TB), patients living with HIV receiving ART remain at a higher risk of developing TB compared to those without HIV. We investigated the incidence of TB and the proportion of HIV-associated TB cases among patients living with HIV who are receiving ART. Methods: The study used TB registration and ART programme data collected between 2008 and 2017 from an integrated, public clinic in urban Lilongwe, Malawi. ART initiation was based on either WHO clinical staging or CD4 cell count. The CD4 thresholds for ART initiation eligibility was initially 250 cells/[micro]L then changed to 350 cells/[micro]L in 2011, 500 cells/[micro]L in 2014 and to universal treatment upon diagnosis from 2016. Using TB registration data, we calculated the proportion of TB/HIV patients who were already on ART when they registered for TB treatment by year of TB registration. ART registration data were used to examine TB incidence by calendar year of ART follow-up and by time on ART. Results: The overall proportion of TB/patients living with HIV who started TB treatment while on ART increased from 21% in 2008 to 81% in 2017 but numbers remained relatively constant at 500 TB cases annually. The overall incidence rate of TB among patients on ART was 1.35/100 person-years (95% CI 1.28 to 1.42). The incidence of TB by time on ART decreased from 6.4/100 person-years in the first three months of ART to 0.4/100 person-years after eight years on ART. TB incidence was highest in the first month on ART. The annual rate of TB among patients on ART rapidly decreased each calendar year and stabilized at 1% after 2013. Although the risk of developing TB decreased with year of ART initiation in univariable analysis, there was no significant association after adjusting for sex, age and reason for ART eligibility. Conclusions: The decline in TB incidence over calendar years suggests protective effects of early ART initiation. The high TB incidence within the first month of ART highlights the need for more sensitive tools such as X-ray and GeneXpert to identify patients living with HIV who have clinical and subclinical TB disease at ART initiation. Keywords: Antiretroviral therapy; HIV; Tuberculosis; Incidence; Patients living with HIV; Malawi, 1 | INTRODUCTION Despite recent declining incidence, tuberculosis (TB) is the leading cause of morbidity and mortality among people living with HIV [1]. In 2015, an estimated 1.2 million TB [...]

: Introduction: HIV diagnosis is the necessary first step towards HIV care initiation, yet many persons living with HIV (PLWH) remain undiagnosed. Employing multiple HIV testing strategies in tandem could increase HIV detection and promote linkage to care. We aimed to assess an intervention to improve HIV detection within socio‐sexual networks of PLWH in two sexually transmitted infections (STI) clinics in Lilongwe, Malawi. Methods: We conducted a randomized controlled trial to evaluate an intervention combining acute HIV infection (AHI) screening, contract partner notification and social contact referral versus the Malawian standard of care: serial rapid serological HIV tests and passive partner referral. Enrolment occurred between 2015 and 2019. HIV‐seropositive persons (two positive rapid tests) were randomized to the trial arms and HIV‐seronegative (one negative rapid test) and ‐serodiscordant (one positive test followed by a negative confirmatory test) persons were screened for AHI with HIV RNA testing. Those found to have AHI were offered enrolment into the intervention arm. Our primary outcome of interest was the number of new HIV diagnoses made per index participant within participants’ sexual and social networks. We also calculated total persons, sexual partners and PLWH (including those previously diagnosed) referred per index participant. Results: A total of 1230 HIV‐seropositive persons were randomized to the control arm, and 561 to the intervention arm. Another 12,713 HIV‐seronegative or ‐serodiscordant persons underwent AHI screening, resulting in 136 AHI cases, of whom 94 enrolled into the intervention arm. The intervention increased the number of new HIV diagnoses made per index participant versus the control (ratio: 1.9; 95% confidence interval (CI): 1.2 to 3.1). The intervention also increased the numbers of persons (ratio: 2.5; 95% CI: 2.0 to 3.2), sexual partners (ratio: 1.7; 95% CI: 1.4 to 2.0) and PLWH (ratio: 2.3; 95% CI: 1.7 to 3.2) referred per index participant. Conclusions: Combining three distinct HIV testing and referral strategies increased the detection of previously undiagnosed HIV infections within the socio‐sexual networks of PLWH seeking STI care. Combination HIV detection strategies that leverage AHI screening and socio‐sexual contact networks offer a novel and efficacious approach to increasing HIV status awareness., INTRODUCTION HIV diagnosis is the essential first step for people living with HIV (PLWH) to access HIV care, which can improve health outcomes and reduce the potential for onward transmission [...]

: Introduction: Eighty percent of adolescents living with perinatally and behaviourally acquired HIV live in sub‐Saharan Africa (SSA), a continent with marked economic inequality. As part of our global project describing adolescents living with perinatally acquired HIV (APH), we aimed to assess whether inequality in outcomes exists by country income group (CIG) for APH within SSA. Methods: Through the CIPHER cohort collaboration, individual retrospective data from 7 networks and 25 countries in SSA were included. APH were included if they entered care at age 10 years. World Bank CIG classification for median year of first visit was used. Cumulative incidence of mortality, transfer‐out and loss‐to‐follow‐up was calculated by competing risks analysis. Mortality was compared across CIG by Cox proportional hazards models. Results: A total of 30,296 APH were included; 50.9% were female and 75.7% were resident in low‐income countries (LIC). Median [interquartile range (IQR)] age at antiretroviral therapy (ART) start was 8.1 [6.3; 9.5], 7.8 [6.2; 9.3] and 7.3 [5.2; 8.9] years in LIC, lower‐middle income countries (LMIC) and upper‐middle income countries (UMIC) respectively. Median age at last follow‐up was 12.1 [10.9; 13.8] years, with no difference between CIG. Cumulative incidence (95% CI) for mortality between age 10 and 15 years was lowest in UMIC (1.1% (0.8; 1.4)) compared to LIC (3.5% (3.1; 3.8)) and LMIC (3.9% (2.7; 5.4)). Loss‐to‐follow‐up was highest in UMIC (14.0% (12.9; 15.3)) compared to LIC (13.1% (12.4; 13.8)) and LMIC (8.3% (6.3; 10.6)). Adjusted mortality hazard ratios (95% CI) for APH in LIC and LMIC in reference to UMIC were 2.50 (1.85; 3.37) and 2.96 (1.90; 4.61) respectively, with little difference when restricted only to APH who ever received ART. In adjusted analyses mortality was similar for male and female APH. Conclusions: Results highlight probable inequality in mortality according to CIG in SSA even when ART was received. These findings highlight that without attention towards SDG 10 (to reduce inequality within and among countries), progress towards ensuring healthy lives and promoting wellbeing for all at all ages (SDG 3) will be hampered for APH in LIC and LMIC., Introduction Sub‐Saharan Africa (SSA) is a complex region marked by diversity and inequality. Across the continent gross national income per capita varies almost thirty fold from 160/1000. Sub‐Saharan Africa is [...]

Background: In Malawi, as in other sub‐Saharan African countries, nurses manage patients of all ages on antiretroviral treatment (ART). Nurse management of children is rarely studied. We compare ART prescribing between nurses and clinical officers during routine clinic visits at an urban, public clinic to inform policy in paediatric ART management. Methods: Caregivers of children on first‐line ART provided information about visit dates, pill counts, ART dosage and formulation to a nurse and, subsequently, to a clinical officer. Nurses and clinical officers independently calculated adherence, dosage based on body weight, and set next appointment date. Clinical officers, but not nurses, accessed an electronic data system that made the calculations for them based on information from prior visits, actual and expected pill consumption, and standard drug supplies. Nurses calculated with pen and paper. For numerical variables, Bland‐Altman graphs plot differences of each nurse–clinical officer pair against the mean, show the 95% limits of agreement (LoA), and also show the mean difference across all reviews. Kappa statistics assess agreement for categorical variables. Results: A total of 704 matched nurse–clinical officer reviews of 367 children attending the ART clinics between March and July 2010 were analyzed. Eight nurses and 18 clinical officers were involved; two nurses and five clinical officers managed 100 visits or more. Overall, there was a good agreement between the two cadres. Differences between nurses and clinical officers were within narrow LoA and mean differences showed little deviation from zero, indicating little skewing towards one cadre. LoA of adherence and morning and evening ART dosages varied from −24% to 24%, −0.4 to 0.4 and −0.41 to 0.40 tablets, respectively, with mean differences (95% CI) of 0.003 (−0.9, 0.91), −0.005 (−0.02, 0.01) and −0.009 (−0.02, 0.01). Next appointment calculations differed more between cadres with LoA from −40 to 42 days [mean difference: 0.96 days (95% CI:−0.6 to 2.5)], but agreement in the ART formulation prescribed was very good (kappa 0.93). Conclusions: Nurses’ ART prescribing practices and calculations of adherence and next appointments are similar to clinical officers, although clinical officers used an electronic system. Our findings support the decision of Malawi's health officials to utilize nurses to manage paediatric ART patients., Background Consistent adherence to dosing guidelines by health providers and patients is essential to reduce the likelihood of treatment failure from under dosing or drug toxicity from overdosing. Choosing the [...]