Background Heterologous prime-boost vaccination with ChAd63 and MVA encoding ME-TRAP has shown acceptable safety and promising immunogenicity in African adult and pediatric populations. If licensed, this vaccine could be given to infants receiving routine childhood immunizations. We therefore evaluated responses to ChAd63 MVA ME-TRAP when co-administered with routine Expanded Programme on Immunization (EPI) vaccines. Methods We enrolled 65 Gambian infants and neonates, aged sixteen, eight or one week at first vaccination and randomized them to receive either ME-TRAP and EPI vaccines or EPI vaccines only. Safety was assessed by the description of vaccine-related adverse events. Immunogenicity was evaluated using IFNγ ELISpot, whole-blood flow cytometry and anti-TRAP IgG ELISA. Serology was performed to confirm all infants achieved protective titers to EPI vaccines. Results The vaccines were well tolerated in all age groups with no vaccine-related serious adverse events. High-level TRAP specific IgG and T cell responses were generated after boosting with MVA. CD8+ T cell responses, previously found to correlate with protection, were induced in all groups. Antibody responses to EPI vaccines were not altered significantly. Conclusion Malaria vectored prime-boost vaccines co-administered with routine childhood immunizations were well tolerated. Potent humoral and cellular immunity induced by ChAd63 MVA ME-TRAP did not reduce the immunogenicity of co-administered EPI vaccines, supporting further evaluation of this regimen in infant populations. Trial registration The clinical trial was registered on Clinicaltrials.gov (NCT02083887) and the Pan-African Clinical Trials Registry (PACTR201402000749217).
High early mortality rate among HIV infected patients following initiation of antiretroviral therapy (ART) in resource limited settings may indicate high pre-treatment mortality among ART-eligible patients. There is dearth of data on pre-treatment mortality in ART programmes in sub-Sahara Africa. This study aims to determine pre-treatment mortality rate and predictors of pre-treatment mortality among ART-eligible adult patients in a West Africa clinic-based cohort.All HIV-infected patients aged 15 years or older eligible for ART between June 2004 and September 2009 were included in the analysis. Assessment for eligibility was based on the Gambia ART guideline. Survival following ART-eligibility was determined by Kaplan-Meier estimates and predictors of pre-treatment mortality determined by Cox proportional hazard models.Overall, 790 patients were assessed as eligible for ART based on their clinical and/or immunological status among whom 510 (64.6%) started treatment, 26 (3.3%) requested transfer to another health facility, 136 (17.2%) and 118 (14.9%) were lost to follow-up and died respectively without starting ART. ART-eligible patients who died or were lost to follow-up were more likely to be male or to have a CD4 T-cell count < 100 cells/μL, while patients in WHO clinical stage 3 or 4 were more likely to die without starting treatment. The overall pre-treatment mortality rate was 21.9 deaths per 100 person-years (95% CI 18.3 - 26.2) and the rate for the composite end point of death or loss to follow-up was 47.1 per 100 person-years (95% CI 41.6 - 53.2). Independent predictors of pre-treatment mortality were CD4 T-cell count <100 cells/μL (adjusted Hazard ratio [AHR] 3.71; 95%CI 2.54 - 5.41) and WHO stage 3 or 4 disease (AHR 1.91; 95% CI 1.12 - 3.23). Forty percent of ART-eligible patients lost to follow-up seen alive at field visit cited difficulty with the requirement of disclosing their HIV status as reason for not starting ART.Approximately one third of ART-eligible patients did not start ART and pre-treatment mortality rate was found high among HIV infected patients in our cohort. CD4 T-cell count <100 cells/μL is the strongest independent predictor of pre-treatment mortality. The requirement to disclose HIV status as part of ART preparation counselling constitutes a huge barrier for eligible patients to access treatment.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is evolving differently in Africa than in other regions. Africa has lower SARS-CoV-2 transmission rates and milder clinical manifestations. Detailed SARS-CoV-2 epidemiologic data are needed in Africa. We used publicly available data to calculate SARS-CoV-2 infections per 1,000 persons in The Gambia. We evaluated transmission rates among 1,366 employees of the Medical Research Council Unit The Gambia (MRCG), where systematic surveillance of symptomatic cases and contact tracing were implemented. By September 30, 2020, The Gambia had identified 3,579 SARS-CoV-2 cases, including 115 deaths; 67% of cases were identified in August. Among infections, MRCG staff accounted for 191 cases; all were asymptomatic or mild. The cumulative incidence rate among nonclinical MRCG staff was 124 infections/1,000 persons, which is >80-fold higher than estimates of diagnosed cases among the population. Systematic surveillance and seroepidemiologic surveys are needed to clarify the extent of SARS-CoV-2 transmission in Africa.
Abstract Background Most tuberculosis (TB) cases in The Gambia are notified in the Greater Banjul Area (GBA). We conducted an Enhanced-Case-Finding (ECF) intervention in the GBA and determined its effect on TB incidence and ongoing TB transmission. Methods This was a cluster randomized trial in which randomly assigned intervention areas of grouped settlements received three rounds of an ECF strategy consisting of sensitization followed by auramine microscopy, whereas TB patients in control areas continued to be identified through passive case finding. The primary outcome was TB incidence rate. To exclude that an increase in notified cases, followed by a decrease in notified cases, would hide the future impact of the intervention, we tested for changes in transmission dynamics using both genetic clustering and phylodynamic methods. Results No significant difference in TB incidence rates, transmission clustering or effective reproductive number was detected between intervention and control areas. Conclusion Although we did not find evidence for decreased TB incidence nor TB transmission through the ECF strategy used, this approach is an examplar of how both classical epidemiology and genomic phylodynamics approaches can be integrated to better assess public health intervention outcomes.
We followed 205 HIV-infected adults on antiretroviral therapy for at least 12 weeks in a Gambian clinic, where routine viral load monitoring was performed. The 1- and 4-week self-reported adherence and timeliness in keeping to scheduled appointments were recorded at each visit. Seventy patients had measurable viremia between the 12th week and the 3rd year of therapy. Survival analysis of the first detectable viral load on therapy demonstrated an association with 4-week (hazard ratio [HR] 2.6, 95% confidence interval [CI] 1.5-4.3, P = .001) and 1-week (HR 1.9, 95% CI 1.1-3.3, P = .024) self-reported suboptimal adherence and with 1 to 15 days of late presentation for appointments (HR 1.6-1.8, P .027-.109). In a multiple regression model, only 4-week self-reported adherence remained as a significant predictor of viremia.
Background Recent global estimates show that P. falciparum malaria still constitutes an enormous public health concern. Chief amongst desirable interventions is an effective vaccine that could complement existing control measures. Heterologous prime-boost vaccinations involving chimpanzee adenovirus 63 (ChAd63) and modified vaccinia Ankara (MVA) encoding ME-TRAP have consistently shown acceptable safety, excellent immunogenicity and substantial efficacy in African adult and paediatric populations. When licensed, malaria vaccines would preferably be given to infants receiving routine childhood immunisations. Nevertheless, no studies have evaluated the interference of ChAd63/MVA ME-TRAP when co-administered with routine Expanded Programme Immunisation (EPI) vaccines. Methods We enrolled 65 Gambian infants and neonates in an age de-escalating fashion, priming at 4 months, 8 weeks or 1 week of age, and randomised them to vaccine or control (EPI vaccines only) arm. Safety was assessed by the description of vaccine-related adverse events ascertained through clinical assessments, biochemical and haematological tests. Immunogenicity was evaluated by IgG ELISA, interferon-gamma ELISPOT, intra-cellular cytokine staining and flow cytometry. Antibody testing was performed to assess any interference of the EPI vaccines with responses to ChAd63/MVA ME-TRAP. Results Overall, the vaccination regimes were well tolerated in all age groups with no vaccine-related serious adverse events. High level IgG and antigen-specific T cell responses were generated after boosting with MVA, with T cell responses highest in the infants 8 week old at priming dose. EPI vaccines retained unchanged antibody levels in all age groups. Conclusions Potent humoral and cellular immunity induced by heterologous prime-boost immunisation with ChAd63 and MVA ME-TRAP did not interfere with the immunogenicity of co-administered routine EPI vaccines in infants and neonates. Potent T cell induction was again observed with the vectored malaria vaccines despite co-administration with EPI vaccines.
Health systems in sub-Saharan Africa have remained overstretched from dealing with endemic diseases, which limit their capacity to absorb additional stress from new and emerging infectious diseases. Against this backdrop, the rapidly evolving COVID-19 pandemic presented an additional challenge of insufficient hospital beds and human resource for health needed to deliver hospital-based COVID-19 care. Emerging evidence from high-income countries suggests that a 'virtual ward' (VW) system can provide adequate home-based care for selected patients with COVID-19, thereby reducing the need for admissions and mitigate additional stress on hospital beds. We established a VW at the Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, a biomedical research institution located in The Gambia, a low-income west African country, to care for members of staff and their families infected with COVID-19. In this practice paper, we share our experience focusing on the key components of the system, how it was set up and successfully operated to support patients with COVID-19 in non-hospital settings. We describe the composition of the multidisciplinary team operating the VW, how we developed clinical standard operating procedures, how clinical oversight is provided and the use of teleconsultation and data capture systems to successfully drive the process. We demonstrate that using a VW to provide an additional level of support for patients with COVID-19 at home is feasible in a low-income country in sub-Saharan Africa. We believe that other low-income or resource-constrained settings can adopt and contextualise the processes described in this practice paper to provide additional support for patients with COVID-19 in non-hospital settings.
There is little data on responses to combination antiretroviral therapy (cART) among HIV-infected children in the West African region. We describe treatment outcomes among HIV-1 and HIV-2 infected children initiating cART in a research clinic in The Gambia, West Africa. All treatment naive HIV-infected children who initiated cART according to the WHO ART guidelines for children between October 2004 and December 2009 were included in the analysis. Kaplan-Meir estimates and sign-rank test were used to investigate the responses to treatment. 65 HIV-1 and five HIV-2 infected children aged < 15 years were initiated on cART over this time period. HIV-1 infected children were treated with a combination of Zidovudine or Stavudine + Lamivudine + Nevirapine or Efavirenz while children with HIV-2 were treated with Zidovudine + Lamivudine + ritonavir-boosted Lopinavir. HIV-1 infected children were followed-up for a median (IQR) duration of 20.1 months (6.9 – 34.3), with their median (IQR) age at treatment initiation, CD4% and plasma viral load at baseline found to be 4.9 years (2.1 – 9.1), 13.0% (7.0 – 16.0) and 5.4 log10 copies/ml (4.4 – 6.0) respectively. The median age at treatment initiation of the five HIV-2 infected children was 12 years (range: 4.6 – 14.0) while their median baseline CD4+ T cell count and HIV-2 viral load were 140 cells/mm3 (Range: 40 – 570 cells/mm3) and 4.5 log10copies/mL (Range: 3.1 - 4.9 log10copies/mL) respectively. Among HIV-1 infected children <5 years of age at ART initiation, the median (IQR) increases in CD4% from baseline to 12, 24 and 36 months were 14% (8 – 19; P = 0.0004), 21% (15 – 22; P = 0.005) and 15% (15 – 25; P = 0.0422) respectively, while the median (IQR) increase in absolute CD4 T cell count from baseline to 12, 24 and 36 months for those ≥5 years at ART initiation were 470 cells/mm3 (270 – 650; P = 0.0005), 230 cells/mm3 (30 – 610; P = 0.0196) and 615 cells/mm3 (250 – 1060; P = 0.0180) respectively. The proportions of children achieving undetectable HIV-1 viral load at 6-, 12-, 24- and 36 months of treatment were 24/38 (63.2%), 20/36 (55.6%), 8/22 (36.4%) and 7/12 (58.3%) respectively. The probability of survival among HIV-1 infected children after 12 months on ART was 89.9% (95% CI 78.8 – 95.3). CD4 T cell recovery was sub-optimal in all the HIV-2 infected children and none achieved virologic suppression. Two of the HIV-2 infected children died within 6 months of starting treatment while the remaining three were lost to follow-up. The beneficial effects of cART among HIV-1 infected children in our setting are sustained in the first 24 months of treatment with a significant improvement in survival experience up to 36 months; however the outcome was poor in the few HIV-2 infected children initiated on cART.
At the beginning of the COVID-19 pandemic, in early 2020, the scientific community hypothesised that SARS-CoV-2 transmission would eventually be hindered by herd immunity, conferred by natural infection, vaccination, or both.1Fontanet A Cauchemez S COVID-19 herd immunity: where are we?.Nat Rev Immunol. 2020; 20 (1Fontanet A, Cauchemez S.): 583-584Crossref PubMed Scopus (373) Google Scholar However, essential questions about whether infection with SARS-CoV-2 confers protection against reinfection and the length of time the protection lasts after either infection or vaccination remain open. These answers are crucial for the development of appropriate health control measures worldwide and become more important as new viral variants spread. By March 15, 2021, fewer than 100 reinfections had been reported worldwide, mainly in countries with a high mortality burden. In most cases, reinfections were less severe than the initial infection.2Lee JS Kim SY Kim TS et al.Evidence of severe acute respiratory syndrome coronavirus 2 reinfection after recovery from mild coronavirus disease 2019.Clin Infect Dis. 2020; (published online Nov 21.)https://doi.org/10.1093/cid/ciaa1421Crossref Scopus (53) Google Scholar, 3Hansen CH Michlmayr D Gubbels SM Mølbak K Ethelberg S Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study.Lancet. 2021; 397: 1204-1212Summary Full Text Full Text PDF PubMed Scopus (438) Google Scholar However, recent reports from Brazil, a country that in parts surpassed the threshold of herd immunity after the first wave but had a similarly strong second wave,4Sabino EC Buss LF Carvalho MPS et al.Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence.Lancet. 2021; 397: 452-455Summary Full Text Full Text PDF PubMed Scopus (546) Google Scholar are worrisome. Such resurgence of COVID-19 cases in the second wave can be explained by rapid waning immunity, the expansion of the new SARS-Co-V-2 variants that might evade immunity generated in response to previous infections (ie, B.1.1.7, B.1.351, and P.1), higher transmissibility of new lineages that require a larger herd immunity, or a combination of all these factors.4Sabino EC Buss LF Carvalho MPS et al.Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence.Lancet. 2021; 397: 452-455Summary Full Text Full Text PDF PubMed Scopus (546) Google Scholar Reinfections in west Africa, a region with a lower toll of infections and deaths5WorldometerCOVID-19 coronavirus pandemic.https://www.worldometers.info/coronavirus/Date accessed: April 5, 2021Google Scholar than Europe, North America, or South America, are yet to be described. We aimed to ascertain whether any reinfections had occurred in The Gambia. The Gambia is the smallest country in west Africa, with 4712 cases and 150 deaths reported by March 1, 2021, although the number of cases is probably underestimated.5WorldometerCOVID-19 coronavirus pandemic.https://www.worldometers.info/coronavirus/Date accessed: April 5, 2021Google Scholar At that time, 460 SARS-CoV-2 genomes from confirmed cases had been sequenced in the country, with 430 (93·5%) genomes already submitted on the GISAID database.6GISAIDPhylodynamics of pandemic coronavirus in west Africa.https://www.gisaid.org/phylodynamics/west-africa/Date: 2021Date accessed: April 5, 2021Google Scholar Among these samples, only two main lineages of the virus, lineages A and B, have been detected. Lineage B constitutes almost 98% of the total genomes sequenced, with the sub-lineage B.1 being the most prevalent, found in 20% of the sequences. Naso-oropharyngeal samples are collected as part of the national surveillance and by the Medical Research Council Unit The Gambia (MRCG) at the London School of Hygiene and Tropical Medicine through clinical, occupational health, and research activities, including the PaTS trial (NCT04703608), from symptomatic individuals or contacts of known COVID-19 cases. Screening of asymptomatic health-care workers and those proposing to travel across international borders also takes place. The standard test for COVID-19 diagnosis in The Gambia, as of March 15, 2021, is real-time PCR of SARS-CoV-2 specific viral gene sequences. Confirmation of reinfections were done by genomic analysis. Library preparation and sequencing were done using the ARTIC (version 3) protocol for SARS-CoV-2 that targeted whole genome sequencing.7Quick J nCoV-2019 sequencing protocol v3 (LoCost) V.3.https://www.protocols.io/view/ncov-2019-sequencing-protocol-v3-locost-bh42j8yeDate: 2020Date accessed: March 1, 2021Google Scholar Libraries were pooled in multiplexes of 24 per flow cell and sequenced on a GridION platform (Oxford Nanopore Technologies, UK). Bioinformatics analysis was done using the ARTIC (version 3) bioinformatics pipeline for SARS-CoV-2 genome analysis.8Loman N Rowe W Rambaut A nCoV-2019 novel coronavirus bioinformatics protocol.https://artic.network/ncov-2019/ncov2019-bioinformatics-sop.htmlDate: 2020Date accessed: March 1, 2021Google Scholar Genome alignments against the reference were visualised on the Interactive Genomics Viewer.9Thorvaldsdóttir H Robinson JT Mesirov JP Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration.Brief Bioinform. 2013; 14: 178-192Crossref PubMed Scopus (5713) Google Scholar Mutations were confirmed using the GISAID CoVsurver.10GISAIDCoVsurver: mutation analysis of hCoV-19.https://www.gisaid.org/epiflu-applications/covsurver-mutations-app/Date accessed: February 17, 2021Google Scholar Lineage assignment was done using Pangolin (version 2.3.0).11GitHubPangolin.https://github.com/cov-lineages/pangolinDate: 2020Date accessed: March 1, 2021Google Scholar The Gambian Government and MRCG joint ethics committee approved the study presented here (Ref L2021.E04). We have phylogenetically confirmed two reinfections among healthy Gambian individuals aged 31 years and 36 years, with a time lag of 5 months and 6 months, respectively. Both individuals had mild symptoms during the second infection that lasted less than 1 week. For the initial infection, one individual had mild symptoms, whereas the other was asymptomatic (tested as a contact of a positive case). Epidemiological, clinical, and molecular details of both infections are shown in the table.TableClinical, epidemiological, and molecular characteristics of the two individuals with SARS-CoV-2 reinfectionsPatient APatient BSexFemaleFemaleAge, years3136ComorbiditiesNoneNoneFirst infectionDate of infectionAug 30, 2020July 31, 2020Clinical presentationWHO criteria for mild infection*Symptomatic patient meeting the case definition for COVID-19 without evidence of viral pneumonia or hypoxia.AsymptomaticCt value ORF-1/N gene36·7/34·1Negative/38·0LineageB.1 (discovered in March, 2020, in the UK, Mexico, and USA)B.1.235 (discovered January, 2020, in the UK, USA, and Spain)Second infectionDate of infectionJan 21, 2021Feb 1, 2021Clinical presentationWHO criteria for mild infection*Symptomatic patient meeting the case definition for COVID-19 without evidence of viral pneumonia or hypoxia.WHO criteria for mild infection*Symptomatic patient meeting the case definition for COVID-19 without evidence of viral pneumonia or hypoxia.Ct value E gene/N gene34·0/33·120·9/19·1LineageB.1.1.74 (discovered in March, 2020, in the UK, Ireland, and Belgium)B.1 (discovered in March, 2020, in the UK, Mexico, and USA)Ct=cycle threshold. ORF-1=open reading frame 1.* Symptomatic patient meeting the case definition for COVID-19 without evidence of viral pneumonia or hypoxia. Open table in a new tab Ct=cycle threshold. ORF-1=open reading frame 1. Genome-wide sequence comparisons for the two viruses of each patient to the reference shows mutations on the S gene, which encodes for the virus spike protein (appendix p 3). The spike protein mediates receptor recognition and binding during infection, playing an important part in viral transmission.12Huang Y Yang C Xu XF Xu W Liu SW Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19.Acta Pharmacol Sin. 2020; 41: 1141-1149Crossref PubMed Scopus (1401) Google Scholar Although it is still unclear as to what extent immune responses against a previous variant will protect against reinfection by a different variant, mutations of the viral spike protein are predicted to enhance infectivity.13Zhang L Jackson CB Mou H et al.SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity.Nat Commun. 2020; 116013Crossref Scopus (613) Google Scholar In both patients, we have seen more mutations in the S gene in the variants from the second infection episodes than in those from the first episode (two amino-acid changing mutations in the first infection and four in the second infection). One of these mutations associated with enhanced infectivity (D614G)14Ozono S Zhang Y Ode H et al.SARS-CoV-2 D614G spike mutation increases entry efficiency with enhanced ACE2-binding affinity.Nat Commun. 2021; 12: 848Crossref PubMed Scopus (316) Google Scholar was present in all four infections. Certain mutations on the receptor-binding domain of the spike protein confer resistance to commonly elicited antibodies during SARS-CoV-2 infection in vitro.15Weisblum Y Schmidt F Zhang F et al.Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants.eLife. 2020; 9: 9Crossref Scopus (888) Google Scholar One such mutation is N440K, detected in patient A's reinfection. Other mutations identified include A1020S, which is involved in viral oligomerisation interfaces; and G946V, detected in the last quarter of 2020 among different variants, including B.1.1.7. Overall, these reinfections are potentially a consequence of divergent mutations enhancing transmission of the virus, but this will need to be assessed in a larger pool of reinfected individuals. Two (B.1·235 and B.1.1.74) of the three lineages involved in these two reinfections are uncommon in the country, representing 3% and less than 1% of the Gambian isolates, respectively.6GISAIDPhylodynamics of pandemic coronavirus in west Africa.https://www.gisaid.org/phylodynamics/west-africa/Date: 2021Date accessed: April 5, 2021Google Scholar In summary, our data conclude that at least two reinfections have occurred in The Gambia. These events have occurred in healthy young individuals infected with similar viral variants in the first and second episode. If reinfections with similar strains are possible, herd immunity in west Africa could take longer than expected as a large majority of cases are asymptomatic or with mild disease and these probably develop weaker immune responses.16Long QX Tang XJ Shi QL et al.Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections.Nat Med. 2020; 26: 1200-1204Crossref PubMed Scopus (2031) Google Scholar In the absence of widespread vaccination, reinfections could become more common when the new variants become predominant in the region. Community-based immunological studies are urgently needed. We declare no competing interests. We thank the Prevention and Treatment of COVID-19 Associated Severe Pneumonia (PaTS) field team (led by Mr Bakary Dibba) and the PaTS support teams: the research support (led by Asheme Mahmoud), clinical trials support, transport, and operations teams. We are also grateful to the entire staff of the COVID-19 Risk Coordinating team. We acknowledge the excellent technical support by the diagnostic teams from PaTS, the unit COVID-19 diagnostics, and The Gambia National Public Health Laboratory. This study was funded by the UK Research and Innovation as part of the COVID-19 strategic priorities supplementary funding for the Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine (grant reference MC_PC_19084). Download .pdf (.21 MB) Help with pdf files Supplementary appendix
HIV infection among children, particularly those under 24 months of age, is often rapidly progressive; as a result guidelines recommend earlier access to combination antiretroviral therapy (cART) for HIV infected children. Losses to follow-up (LTFU) and death in the interval between diagnosis and initiation of ART profoundly limit this strategy. This study explores correlates of LTFU and death prior to ART initiation among children.The study is based on 337 HIV-infected children enrolled into care at an urban centre in The Gambia, including those alive and in care when antiretroviral therapy became available and those who enrolled later. Children were followed until they started ART, died, transferred to another facility, or were LTFU. Cox proportional hazards regression models were used to determine the hazard of death or LTFU according to the baseline characteristics of the children.Overall, 223 children were assessed as eligible for ART based on their clinical and/or immunological status among whom 73 (32.7%) started treatment, 15 (6.7%) requested transfer to another health facility, 105 (47.1%) and 30 (13.5%) were lost to follow-up and died respectively without starting ART. The median survival following eligibility for children who died without starting treatment was 2.8 months (IQR: 0.9 - 5.8) with over half (60%) of all deaths occurring at home. ART-eligible children less than 2 years of age and those in WHO stage 3 or 4 were significantly more likely to be LTFU when compared with their respective comparison groups. The overall pre-treatment mortality rate was 25.7 per 100 child-years of follow-up (95% CI 19.9 - 36.8) and the loss to programme rate was 115.7 per 100 child-years of follow-up (95% CI 98.8 - 137). In the multivariable Cox proportional hazard model, significant independent predictors of loss to programme were being less than 2 years of age and WHO stage 3 or 4. The Adjusted Hazard Ratio (AHR) for loss to programme was 2.06 (95% CI 1.12 - 3.83) for being aged less than 2 years relative to being 5 years of age or older and 1.92 (95% CI 1.05 - 3.53) for being in WHO stage 3 or 4 relative to WHO stage 1 or 2.Earlier enrolment into HIV care is key to achieving better outcomes for HIV infected children in developing countries. Developing strategies to ensure early diagnosis, elimination of obstacles to prompt initiation of therapy and instituting measures to reduce losses to follow-up, will improve the overall outcomes of HIV-infected children.
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