Objectives To assess the proportion of patients lost to programme (died, lost to follow-up, transferred-out) between HIV diagnosis and start of antiretroviral therapy (ART) in sub-Saharan Africa, and determine factors associated with loss to programme. Methods Systematic review and meta-analysis. We searched PubMed and EMBASE databases for studies in adults. Outcomes were the percentage of patients dying before starting ART, the percentage lost to follow-up, the percentage with a CD4 cell count, the distribution of first CD4 counts and the percentage of eligible patients starting ART. Data were combined using random-effects meta-analysis. Results 29 studies from sub-Saharan Africa including 148,912 patients were analysed. 6 studies covered the whole period from HIV diagnosis to ART start. Meta-analysis of these studies showed that of 100 patients with a positive HIV test, 72 (95% CI 60–84) had a CD4 cell count measured, 40 (95% CI 26–55) were eligible for ART and 25 (95% CI 13–37) started ART. There was substantial heterogeneity between studies (p<0.0001). Median CD4 cell count at presentation ranged from 154 cells/μl to 274 cells/μl. Patients eligible for ART were less likely to become lost to programme (25% versus 54%, p<0.0001) but eligible patients were more likely to die (11% versus 5%, p<0.0001) than ineligible patients. Loss to programme was higher in men, in patients with low CD4 cell counts and low socio-economic status, and in recent time periods. Conclusions Monitoring and care in the pre-ART time period needs improvement, with greater emphasis on patients not yet eligible for ART.

IntroductionPatients who are lost to follow-up (LTFU) while on antiretroviral therapy (ART) pose challenges to the long-term success of ART programs. We describe the extent to which patients considered LTFU are misclassified as true disengagement from care when they are still alive on ART and explain reasons for ART discontinuation using our active tracing program to further improve ART retention programs and policies.MethodsWe identified adult ART patients who missed clinic appointment by more than 3 weeks between January 2006 and December 2010, assuming that such patients would miss their doses of antiretroviral drugs. Patients considered LTFU who consented during ART registration were traced by phone or home visits; true ART status after tracing was documented. Reasons for ART discontinuation were also recorded for those who stopped ART.ResultsOf the 4,560 suspected LTFU cases, 1,384 (30%) could not be traced. Of the 3,176 successfully traced patients, 952 (30%) were dead and 2,224 (70%) were alive, of which 2,183 (99.5%) started ART according to phone-based self-reports or physical verification during in-person interviews. Of those who started ART, 957 (44%) stopped ART and 1,226 (56%) reported still taking ART at the time of interview by sourcing drugs from another clinic, using alternative ART sources or making brief ART interruptions. Among 940 cases with reasons for ART discontinuations, failure to remember (17%), too weak/sick (12%), travel (46%), and lack of transport to the clinic (16%) were frequently cited; reasons differed by gender.ConclusionThe LTFU category comprises sizeable proportions of patients still taking ART that may potentially bias retention estimates and misdirect resources at the clinic and national levels if not properly accounted for. Clinics should consider further decentralization efforts, increasing drug allocations for frequent travels, and improving communication on patient transfers between clinics to increase retention and adherence.

Background In December 2019, a pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and has rapidly spread around the world since then. Aim This study aims to understand the research gaps related to COVID-19 and propose recommendations for future research. Methods We undertook a scoping review of COVID-19, comprehensively searching databases and other sources to identify literature on COVID-19 between 1 December 2019 and 6 February 2020. We analysed the sources, publication date, type and topic of the retrieved articles/studies. Results We included 249 articles in this scoping review. More than half (59.0%) were conducted in China. Guidance/guidelines and consensuses statements (n = 56; 22.5%) were the most common. Most (n = 192; 77.1%) articles were published in peer-reviewed journals, 35 (14.1%) on preprint servers and 22 (8.8%) posted online. Ten genetic studies (4.0%) focused on the origin of SARS-CoV-2 while the topics of molecular studies varied. Nine of 22 epidemiological studies focused on estimating the basic reproduction number of COVID-19 infection (R0). Of all identified guidance/guidelines (n = 35), only ten fulfilled the strict principles of evidence-based practice. The number of articles published per day increased rapidly until the end of January. Conclusion The number of articles on COVID-19 steadily increased before 6 February 2020. However, they lack diversity and are almost non-existent in some study fields, such as clinical research. The findings suggest that evidence for the development of clinical practice guidelines and public health policies will be improved when more results from clinical research becomes available.

Objectives To analyse mortality, loss to follow-up (LTFU) and retention on antiretroviral treatment (ART) in the first year of ART across all age-groups in the Malawi national ART programme. Design Cohort study including all patients who started ART in Malawi’s public sector clinics between 2004 and 2007. Methods ART registers were photographed, information entered into a database and merged with data from clinics with electronic records. Rates per 100 patient-years and cumulative incidence of retention were calculated. Subhazard ratios (sHR) of outcomes adjusted for patient and clinic level characteristics were calculated in multivariate analysis, applying competing risk models. Results A total of 117,945 patients contributed 85,246 person-years: 1.0% were infants <2 years, 7.4 % children 2–14, 7.5% young people 15–24, and 84.2% adults 25 years and above. Sixty percent of patients were female: women outnumbered men from age 14 to 35 years. Mortality and LTFU were higher in men from age 20 years. Infants and young people had the highest rates per 100 person-years for mortality (23.0 and 19.4) and LTFU (24.7 and 19.3), and the highest adjusted relative risks compared to age group 25–34 years: sHRs were 1.37 (95%CI 1.17–1.60) and 1.17 (95%CI 1.10–1.25) for death and 1.37 (95%CI 1.18–1.59) and 1.27 (95%CI 1.19–1.35) for LTFU, respectively. Conclusion In this country-wide study patients aged 0–1 and 15–24 years had the highest risk of death and LTFU, and from age 20 and older men were at higher risk than women. Interventions to improve outcomes in these patient groups are required.

Background-The number of patients in need of second-line antiretroviral drugs is increasing in sub-Saharan Africa. We aimed to project the need of second-line antiretroviral therapy (ART) in adults in sub-Saharan Africa up to 2030.

Objectives HIV ‘treatment as prevention’ (TasP) describes early treatment of HIV-infected patients intended to reduce viral load (VL) and transmission. Crucial assumptions for estimating TasP's effectiveness are the underlying estimates of transmission risk. We aimed to determine transmission risk during primary infection, and of the relation of HIV transmission risk to VL. Design Systematic review and meta-analysis. Methods We searched PubMed and Embase databases for studies that established a relationship between VL and transmission risk, or primary infection and transmission risk, in serodiscordant couples. We analyzed assumptions about the relationship between VL and transmission risk, and between duration of primary infection and transmission risk. Results We found 36 eligible articles, based on six different study populations. Studies consistently found that larger VLs lead to higher HIV transmission rates, but assumptions about the shape of this increase varied from exponential increase to saturation. The assumed duration of primary infection ranged from 1.5 to 12 months; for each additional month, the log10 transmission rate ratio between primary and asymptomatic infection decreased by 0.40. Conclusions Assumptions and estimates of the relationship between VL and transmission risk, and the relationship between primary infection and transmission risk, vary substantially and predictions of TasP's effectiveness should take this uncertainty into account.

Loss to follow-up (LTFU) is a common problem in many epidemiological studies. In antiretroviral treatment (ART) programmes for patients with HIV mortality estimates can be biased if the LTFU mechanism is non-ignorable, i.e. mortality differs between lost and retained patients. In this setting, routine procedures for handling missing data may lead to biased estimates. To appropriately deal with non-ignorable LTFU, explicit modeling of the missing data mechanism is needed. This can be based on additional outcome ascertainment for a sample of patients LTFU, for example through linkage to national registries or through survey-based methods. In this paper, we demonstrate how this additional information can be used to construct estimators based on inverse probability weights (IPW) or multiple imputation. We use simulations to contrast the performance of the proposed estimators with methods widely used in HIV cohort research for dealing with missing data. The practical implications of our approach are illustrated using South African ART data which are partially linkable to South African national vital registration data. Our results demonstrate that while IPWs and proper imputation procedures can be easily constructed from additional outcome ascertainment to obtain valid overall estimates, neglecting non-ignorable LTFU can result in substantial bias. We believe the proposed estimators are readily applicable to a growing number of studies where LTFU is appreciable but additional outcome data are available through linkage or surveys of patients LTFU.

The majority of WHO guidelines reported their funding sources and the DOI and COI of external contributors in their guideline documents. However, there is a need for improvement, in particular for reporting of funders and their role, declaration processes, and management of COI.