Achieving a robust mentoring and research capacity program in a LMIC - the BRAINS faculty development model.

BACKGROUND: A research and training program (RTP) was carried out to build the capacity of faculty and improve the culture of research in the College of Medicine, University of Lagos (CMUL), Nigeria. METHODS: Realist-guided mixed methods evaluation of the BRAINS project was carried out using secondary data generated during the 5-years (2015 - 2020) of project implementation. Capacity building workshops and mentored research activities targeted at faculty in the CMUL were conducted. Overall, 1,418 participants attended the workshops in batches. Among the participants, forty-five faculty received grants and were mentored by senior professionals (local & international) to conduct research. Data were extracted from all project-related documents including coursework biodata, workshop evaluation forms, quarterly project reports, and end- of-project reports, submitted by the mentees, minutes of meetings, and the proposal submitted for funding. It was in the form of continuous variables and prose (sentences & stories). Quantitative data were analysed with IBM SPSS statistics version 20. Mean knowledge score and mean difference was calculated, paired t-test was carried out using p < 0.05 to determine statistical significance. The prose was thematically analysed to generate themes and narratives. Both were subsequently combined for interpretation and used to refine the initial programme theory into an evidence-informed theory. RESULTS: Twelve courses were deployed, and 1,418 participants (47.8% males and 52.2% females) from medical, nursing, and allied medical departments were trained. Eighty participants were trained in Responsible Conduct of Research and eighty-one on Manuscript Writing over three years. A comparison of the pre/post-test knowledge scores showed a positive mean difference. Thematic analysis of workshop data produced three thematic domains representing effectiveness and gains namely: cognitive, reward, and behavioural. 45 trainees were awarded grants and mentored, and analysis of mentee's data generated 4 themes: Achieving a robust mentoring program; Benefits of the mentoring program; Resilience in research; Improving the mentoring program. CONCLUSION: By contributing to the body of knowledge available on RTPs, this evaluation identified key components that contributed to the success of the project and developed a model for achieving a robust training and mentoring program which can be replicated in other LMICs.

High acceptability and viral suppression rate for first-Line patients on a dolutegravir-based regimen: An early adopter study in Nigeria.

Nigeria adopted dolutegravir (DTG) as part of first line (1L) antiretroviral therapy (ART) in 2017. However, there is limited documented experience using DTG in sub-Saharan Africa. Our study assessed DTG acceptability from the patient's perspective as well as treatment outcomes at 3 high-volume facilities in Nigeria. This is a mixed method prospective cohort study with 12 months of follow-up between July 2017 and January 2019. Patients who had intolerance or contraindications to non-nucleoside reverse-transcriptase inhibitors were included. Patient acceptability was assessed through one-on-one interviews at 2, 6, and 12 months following DTG initiation. ART-experienced participants were asked about side effects and regimen preference compared to their previous regimen. Viral load (VL) and CD4+ cell count tests were assessed according to the national schedule. Data were analysed in MS Excel and SAS 9.4. A total of 271 participants were enrolled on the study, the median age of participants was 45 years, 62% were female. 229 (206 ART-experienced, 23 ART-naive) of enrolled participants were interviewed at 12 months. 99.5% of ART-experienced study participants preferred DTG to their previous regimen. 32% of particpants reported at least one side effect. "Increase in appetite" was most frequently reported (15%), followed by insomnia (10%) and bad dreams (10%). Average adherence as measured by drug pick-up was 99% and 3% reported a missed dose in the 3 days preceding their interview. Among participants with VL results (n = 199), 99% were virally suppressed (<1000 copies/ml), and 94% had VL <50 copies/ml at 12 months. This study is among the first to document self-reported patient experiences with DTG in sub-Saharan Africa and demonstrated high acceptability of DTG-based regimens among patients. The viral suppression rate was higher than the national average of 82%. Our findings support the recommendation of DTG-based regimen as the preferred 1L ART.

Use of exchange blood transfusion in the management of severe COVID-19 infection in pregnancy: experience from Lagos, Nigeria.

Coronavirus disease 2019 (COVID-19) presents with symptoms that may be mild or severe. The individual with the severe form of the disease usually presents with a constellation of respiratory symptoms typical of acute respiratory distress syndrome. In this report, we present our experience of the successful management of an oxygen-dependent pregnant woman with severe COVID-19 infection who had 2 sessions of partial exchange blood transfusion. We discussed the principles that informed this intervention and the need to adopt this novel approach in the care of severe COVID-19 infection.

Adolescents and Young Adults Knowledge, Adherence and Experiences While on Antiretroviral Therapy in a Tertiary Hospital in Lagos, Nigeria: A Mixed-Method Study.

In Nigeria, there is a paucity of data on knowledge and experiences of adolescents and young adults (AYAs) with HIV and ART, as well as their challenges maintaining optimal adherence. A mixed-method study was carried out between August and September 2018 among AYAs attending Lagos University Teaching Hospital, Nigeria. Data collection was via AYAs' hospital records, standardized questionnaires, and in-depth interviews (IDIs). The 4-day ACTG tool was used to measure adherence. Collected data were analyzed descriptively. Assessment of 34 AYAs comprising 18 (52.9%) males with 28 (82.4%) students revealed an overall knowledge score about ART and its effect of 73.6%. Twenty-five (73.5%) had poor knowledge of the development of resistant strains of HIV due to non-adherence recorded. Optimal adherence (≥95%) was recorded in 20 (58.8%) AYAs. IDI produced 4 themes: (i) reasons for non-adherence, (ii) ensuring optimal adherence, (iii) Social support systems and disclosure, and (iv) stigmatization. Our study provided formative data and revealed areas for intervention to improve knowledge and adherence to ART.

Evaluation of the effects of atazanavir-ritonavir on the pharmacokinetics of lumefantrine in patients living with HIV in Lagos University Teaching Hospital, South-Western Nigeria.

PURPOSE: Atazanavir-ritonavir (ATVr)-based antiretroviral therapy and artemether-lumefantrine (AL) are commonly used drugs for the treatment of human immune deficiency virus (HIV) infection and malaria respectively. However, interaction of both drugs, with Cytochrome P 3A4 (CYP 3A4) isoenzyme, may spawn clinically significant pharmacokinetic interactions. This study evaluated the effects of atazanavir-ritonavir on the pharmacokinetics of lumefantrine. METHOD: In a case-control study, twenty participants having Plasmodium falciparum malaria were recruited and divided into two groups (ATVr-arm, n=10; and control-arm, n= 10). All the participants were administered six oral doses of AL 80-480 mg (Coartem). Thereafter, their blood samples were collected at different time intervals over seven days. The concentration of lumefantrine in each sample was quantified with high-performance liquid chromatography (HPLC) and used to determine its pharmacokinetic parameters which were compared between the test and control groups. RESULTS: ATVr increased the mean day 7 concentration of lumefantrine (ATVr 3847.09 ± 893.35 ng/mL, control 1374.53 ± 265.55 ng/mL, p = 0.016) and the area under its plasma concentration-time curve (ATVr 670529.57 ± 157172.93 ng.h/mL, control 447976.28 ± 80886.99 ng.h/mL, p = 0.224) by 179.88 % and 49.68 %, respectively, but decreased its mean maximum plasma drug concentration (Cmax) (ATVr 13725.70 ± 2658.44 ng/mL, control 15380.48 ± 2332.62 ng/mL, p = 0.645) by 10.76 %. CONCLUSION: ATVr increased drug exposure and day 7 plasma concentration of lumefantrine. AL is therefore considered effective for the treatment of malaria in patients taking ATVr-based regimen. However, the safety associated with the interaction requires further elucidation. TRIAL REGISTRATION: Clin ClinicalTrials.gov Identifier: NCT04531072, August 27, 2020. "Retrospectively registered".

Microscopic and biochemical changes on liver and kidney of Wistar rats on combination antiretroviral therapy: the impact of naringenin and quercetin.

Combination antiretroviral therapy (cART), which is a lifelong therapy for people living with human immunodeficiency virus, has been associated with nephrotoxicity and hepatotoxicity leading to its discontinuation. This study aimed at investigating the ameliorative potential of naringenin and quercetin on cART-induced hepatotoxicity and nephrotoxicity. Seventy male Wistar rats (225-260 g) were divided into seven groups as control, cART, naringenin, quercetin, dimethyl sulfoxide (DMSO), naringenin/cART (CN) and quercetin/cART (CQ). cART (24 mg/kg), naringenin (50 mg/kg) and quercetin (50 mg/kg) were dissolved in 1% v/v DMSO and administered orally for 56 days. Combination of cART and bioflavonoids had significant increase in superoxide dismutase (P < 0.05), catalase (P < 0.01), reduced glutathione (P < 0.001) and decreased malondialdehyde (P < 0.001) compared to cART only. Tumor necrosis factor Alpha (TNFα) level increased significantly in cART and CQ (P < 0.01) groups, while others showed no significant changes compared to control. TNFα also significantly decreased in CQ level compared to cART (P < 0.001). In addition, significant increase in creatinine level in cART only indicated progressive renal toxicity. Also, progressive pathological changes including congested blood vessels and hepatocellular necrosis were found in the liver, while the kidney had glomerular atrophy, and tubular distortion in cART-only group. Control, naringenin- and quercetin-treated groups showed normal renal and hepatic cytoarchitecture. These findings elucidate that progressive renal and hepatic toxicity is associated with the continuous use of cART; however, a combination of quercetin and naringenin with cART showed possible potential of ameliorating the damages posed by cART.

Effect of nevirapine, efavirenz and lopinavir/ritonavir on the therapeutic concentration and toxicity of lumefantrine in people living with HIV at Lagos University Teaching Hospital, Nigeria.

Patients living with HIV in malarial endemic regions may experience clinically significant drug interaction between antiretroviral and antimalarial drugs. Effects of nevirapine (NVP), efavirenz (EFV) and lopinavir/ritonavir (LPVr) on lumefantrine (LM) therapeutic concentrations and toxicity were evaluated. In a four-arm parallel study design, the blood samples of 40 participants, treated with artemether/lumefantrine (AL), were analysed. Lumefantrine Cmax was increased by 32% (p = 0.012) and 325% (p < 0.0001) in the NVP and LPVr arms respectively but decreased by 62% (p < 0.0001) in the EFV-arm. AUC of LM was, respectively, increased by 50% (p = 0.27) and 328% (p < 0.0001) in the NVP and LPVr arms but decreased in the EFV-arm by 30% (p = 0.019). Median day 7 LM concentration was less than 280 ng/mL in EFV-arm (239 ng/mL) but higher in control (290 ng/mL), NVP (369 ng/mL, p = 0.004) and LPVr (1331 ng/mL, p < 0.0001) arms. There were no clinically relevant toxicities nor adverse events in both control and test arms. Artemether/lumefantrine is safe and effective for treatment of malaria in PLWHA taking NVP and LPVr based ART regimen but not EFV-based regimen.

The impact of HIV-1 subtypes on virologic and immunologic treatment outcomes at the Lagos University Teaching Hospital: A longitudinal evaluation.

INTRODUCTION: HIV is a highly diverse virus with significant genetic variability which may confer biologic differences that could impact on treatment outcomes. MATERIALS AND METHODS: We studied the association between HIV subtypes and immunologic and virologic outcomes in a longitudinal cohort of 169 patients on combination antiretroviral therapy. Participants were followed up for 5 years. Demographic data, CD4 cell count and viral loads (VL) were extracted from medical records. Whole protease gene and codon 1-300 of the reverse transcriptase gene were sequenced and analysed. RESULTS: Sixty-four percent of participants were females with a median age of 35 years. Twelve different subtypes were observed, the commonest being CRF 02_AG (55.0%) and subtypes G (23.1%). All subtypes showed steady rise in CD4 count and there was no difference in proportion who achieved CD4+ cell count rise of ≥100 cells/µL from baseline within 12 months' post-initiation of ART, or ≥350 cells/µL at 60 months' post-initiation. Median time to attaining a rise of ≥350 cells/µL was 24 months (6-48 months). The proportion that achieved undetectable VL at month 6 and 12 post-initiation of ART were comparable across subtypes. At end of 5th year, there was no statistical difference in proportion with virologic failure. CONCLUSION: No association between HIV subtypes and immunologic or virologic response to therapy was observed, suggesting that current first-line ART may have similar efficacy across subtype predominating in South-West Nigeria.

Modeling cerebellar limb dysmetria and impaired spatial memory in rats using lamivudine: A preliminary study.

BACKGROUND AND AIM: Neurodegeneration has been associated with the use of combination antiretroviral therapy (cART). This study is aimed at determining if any constituent of cART can induce cerebellar limb dysmetria and spatial memory impairments. MATERIALS AND METHODS: Forty adult male Wistar rats were randomly grouped into four (n = 10): control (distilled water 0.5 mL); Tenofovir (6 mg/kg); Lamivudine (6 mg/kg) and Efavirenz (12 mg/kg). The following neurobehavioral studies were conducted: open field, beam walk, and Morris water maze. Immunohistochemistry of CD 68 and GFAP were used to test for neuroinflammation and neurodegeneration. RESULTS: There was marked increase in pyknotic pyramidal cells of the hippocampus and ghost Purkinje cells in the cerebellum of treatment groups. There was also a significant increase in oxidative stress in lamivudine and efavirenz groups. In addition, Lamivudine caused a significant increase of microglial and astrocytic activity (p < 0.001, 0.05 respectively) compared to control. The open field test showed a significant decrease (p < 0.0001) of the line crossing performance in the efavirenz, lamivudine and tenofovir (with means: 26.4, 4.6, 17.4 respectively) compared to control (50.6). There was also a significant decrease in the grooming (p < 0.05) and rearing (p < 0.01) in lamivudine group. Whereas, walk latency increased in efavirenz (p < 0.01), and lamivudine (p < 0.0001) compared to control. While hind limb slips significantly increased in efavirenz (p < 0.05) and lamivudine (p < 0.0001) compared with control group. Likewise, Lamivudine and Tenofovir exposed groups experienced a significant delay in the time to identify the hidden platform in compared to control (p < 0.05). CONCLUSION: Lamivudine altered efferent stimuli along the cerebellospinal tracts thereby causing motor impairments. The degenerating Purkinje fibers may have induced marked neurodegeneration in the hippocampus resulting in impaired spatial memory.

A preprogram appraisal of factors influencing research productivity among faculty at college of medicine, University of Lagos.

Background: A defining feature of any university is its dedication to scholarly activities, leading to the generation of knowledge and ideas Research productivity is a measure of achievement of a scholar. The number of research publications in peer-reviewed journals is an important criterion for assessing productivity and prestige in the academia. Aims and Objectives: This cross-sectional descriptive study assessed the level of research productivity (RP) among junior faculty at the College of Medicine, University of Lagos, and investigated factors affecting their research output prior to the implementation of a 5-year training grant funded by the National Institutes of Health. Methods: Seventy junior faculty members attended a pre-program training, and the self-reported number of peer-reviewed publications (PRPs) was used as an indicator. Intrinsic and extrinsic factors influencing RP among the attendees were assessed and ranked. Results: The majority (42/70, 60%) of the respondents had <10 PRPs. The median (interquartile range) number of PRPs was 7 (3-18). A desire for the development of their personal skills, contribution to society, and personal research interests topped the list of intrinsic factors influencing RP. Work flexibility, research autonomy, and scholarly pursuits were the bottom three. A desire for promotion, respect from peers, and increased social standing were the top three extrinsic factors, while monetary incentives, employment opportunities, and the need to attend conferences were the lowest three. The top barriers to RP were lack of resources and lack of mentoring. Perceived older age, lack of time, and motivation were the lowest three barriers. Older age and professional cadre were associated with increased RP (P < 0.05). Conclusion: Among the participants, research output appears to be motivated primarily by a desire for personal development,promotion, and respect from peers. Lack of access to resources was the main barrier to increased RP. These factors may need to be considered when developing programs designed to promote RP.

RésuméContexte: Une caractéristique déterminante de toute université est son dévouement aux activités savantes, menant à la génération de connaissances et d'idées La productivité de la recherche est une mesure du rendement d'un chercheur. Le nombre de publications de recherche dans des revues à comité de lecture est un critère important pour évaluer la productivité et le prestige de l'académie. Buts et objectifs: Cette étude descriptive transversale a évalué le niveau de productivité de la recherche (RP) parmi les professeurs débutants du Collège de médecine de l'Université de Lagos et a examiné les facteurs affectant leurs résultats de recherche avant la mise en œuvre d'une subvention de formation de 5 ans. financé par les National Institutes of Health. Méthodes: Soixante-dix facultés juniors ont suivi une formation préalable au programme et le nombre autodéclaré de publications évaluées par des pairs a été utilisé comme indicateur. Les facteurs intrinsèques et extrinsèques influençant la RP chez les participants ont été évalués et classés. Résultats: La majorité (42/70, 60%) des répondants ont utilisé moins de 10 publications évaluées par des pairs. Le nombre médian (intervalle interquartile) de PRP était de 7 (3­18). Le désir de développer leurs compétences personnelles, leur contribution à la société et leurs intérêts personnels en recherche figuraient en tête de liste des facteurs intrinsèques influençant la productivité de la recherche. La flexibilité du travail, l'autonomie de recherche et les activités universitaires étaient les trois derniers. Un désir de promotion, le respect des pairs et une position sociale accrue étaient les trois principaux facteurs extrinsèques, tandis que les incitations monétaires, les possibilités d'emploi et la nécessité d'assister à des conférences étaient les trois plus faibles. Les principaux obstacles à la productivité de la recherche étaient le manque de ressources et le manque de mentorat. L'âge avancé perçu, le manque de temps et la motivation étaient les trois obstacles les plus bas. L'âge avancé et les cadres professionnels étaient associés à une augmentation de la RP (P <0,05). Conclusion: parmi les participants, les résultats de la recherche semblent être principalement motivés par un désir de développement personnel, de promotion et de respect de la part des pairs. Le manque d'accès aux ressources était le principal obstacle à l'augmentation de la productivité de la recherche. Ces facteurs peuvent devoir être pris en compte lors de l'élaboration de programmes conçus pour promouvoir la productivité de la recherche.

Association between HIV-1 subtype and drug resistance in Nigerian infants.

Background: Many lines of evidence point to HIV-1 subtype-specific differences in the development of drug resistance mutations. While variation between subtype C and others has been extensively explored, there has been less emphasis on subtypes common to West Africa. We examined a previously described national survey of pretreatment drug resistance in HIV-1-infected Nigerian children aged <18 months, to explore the association between subtypes and patterns of resistance. Methods: Five hundred and forty-nine dried blood spots, from 15 early infant diagnostic facilities in Nigeria, were amplified and HIV-1 polymerase was sequenced. Four hundred and twenty-four were analysed for surveillance drug resistance mutations (SDRMs). Associations between subtype and SDRMs were evaluated by Fisher's exact test and logistic regression analysis, controlling for geographical region and exposure. Results: Using the sub-subtypes of HIV-1 G defined by Delatorre et al. (PLoS One 2014. 9: e98908) the most common subtypes were CRF02_AG (174, 41.0%), GWA-I (128, 30.2%), GWA-II (24, 5.7%), GCA (11, 2.6%), A (21, 5.0%) and CRF06_cpx (18, 4.2%). One hundred and ninety infants (44.8%) had ≥1 NNRTI mutation, 92 infants (21.7%) had ≥1 NRTI mutation and 6 infants (1.4%) had ≥1 PI mutation. By logistic regression, 67N was more common in GWA-II/GCA than CRF02_AG (OR 12.0, P = 0.006), as was 70R (OR 23.1, P = 0.007), 184I/V (OR 2.92, P = 0.020), the presence of ≥1 thymidine analogue mutation (TAM) (OR 3.87, P = 0.014), ≥1 type 2 TAM (OR 7.61, P = 0.001) and ≥1 NRTI mutation (OR 3.26, P = 0.005). Conclusions: This dataset reveals differences among SDRMs by subtype; in particular, between the GWA-II and GCA subclades, compared with CRF02_AG and GWA-I.

Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance.

In ART programs in sub-Saharan Africa, a growing proportion of HIV-infected persons initiating first-line antiretroviral therapy (ART) have a history of prior antiretroviral drug use (PAU). We assessed the effect of PAU on the risk of pre-treatment drug resistance (PDR) and virological failure (VF) in a multicountry cohort of HIV-infected adults initiated on a standard non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART. Multivariate logistic regression was used to assess the associations between PAU, PDR and VF (defined as viral load ≥400 cps/mL). Causal mediation analysis was used to assess the proportion of the effect of PAU on VF that could be eliminated by intervening on PDR. Of 2737 participants, 122 (4.5%) had a history of PAU. Participants with PAU had a 7.2-fold (95% CI 4.4-11.7) risk of carrying PDR and a 3.1-fold (95% CI 1.6-6.1) increased risk of VF, compared to antiretroviral-naïve participants. Controlling for PDR would eliminate nearly half the effect of PAU on the risk of VF. Patients with a history of PAU are at increased risk of ART failure, which is to a large extent attributable to PDR. These findings support the recent WHO recommendations for use of differentiated, non-NNRTI-based empiric first-line therapy in patients with PAU.

Correction to: Population data of 21 autosomal STR loci in the Hausa, Igbo and Yoruba people of Nigeria.

In the original paper author Alani Sulaimon Akanmu was erroneously omitted from the author list. Prof. Akanmu has now been added as 4th author. Prof. Akanmu acted as an academic supervisor of the study and additionally contributed to the publication by reading, commenting and editing the manuscript.

PSYCHOACTIVE SUBSTANCE USE AMONG NIGERIAN COHORT WITH HIV/AIDS: FREQUENCY, TYPES AND DEMOGRAPHIC CORRELATES.

Introduction: There are good pointers from literature to the detrimental impacts of psychoactive substance use in HIV/AIDS patients. This study aimed at investigating the prevalence, types and demographic correlates of psychoactive substance use among people living with HIV/AIDS. Methods: The study participants consisted of 295 adults with HIV/AIDS and were interviewed with a designed questionnaire that consisted of two parts. The first part contained questions to elicit socio-demographic and treatment related information of the participants, while the second part focused on psychoactive substance use. Results: The mean (SD) age of participants was 37.6 (±8.6) years, and majority (61.0%) of them were made up of females. Most of the subjects were married, 181 (61.4%) and employed 174 (59.0%). Of the total participants, 64 (21.7%) reported use of a form of psychoactive substance, among which the largest proportion (19.3%) reported use of alcohol, 1.4% use cannabis while 1% admitted to use of nicotine. Following regression analyses, being male (Odds Ratio =2.38; 95% Confidence Interval: 95% CI = 1.26 - 4.49; p=0.008) and increasing educational attainment (Odds Ratio = 1.62; 95% CI: 1.07 - 2.45; p=0.02) correlated positively with psychoactive substance use, while being single (Odds Ratio = 0.59; 95% CI: 0.35 - 0.99; p=0.047) correlated negatively. Conclusion: Proactive and targeted intervention strategies against psychoactive substance use among people living with HIV/AIDS using what is known about vulnerability are implied. Further research on the complex relationship between HIV/AIDS and psychoactive substance use is indicated.

High levels of pre-treatment HIV drug resistance and treatment failure in Nigerian children.

INTRODUCTION: Pre-treatment HIV drug resistance (PDR) is an increasing problem in sub-Saharan Africa. Children are an especially vulnerable population to develop PDR given that paediatric second-line treatment options are limited. Although monitoring of PDR is important, data on the paediatric prevalence in sub-Saharan Africa and its consequences for treatment outcomes are scarce. We designed a prospective paediatric cohort study to document the prevalence of PDR and its effect on subsequent treatment failure in Nigeria, the country with the second highest number of HIV-infected children in the world. METHODS: HIV-1-infected children ≤12 years, who had not been exposed to drugs for the prevention of mother-to-child transmission (PMTCT), were enrolled between 2012 and 2013, and followed up for 24 months in Lagos, Nigeria. Pre-antiretroviral treatment (ART) population-based pol genotypic testing and six-monthly viral load (VL) testing were performed. Logistic regression analysis was used to assess the effect of PDR (World Health Organization (WHO) list for transmitted drug resistance) on subsequent treatment failure (two consecutive VL measurements >1000 cps/ml or death). RESULTS: Of the total 82 PMTCT-naïve children, 13 (15.9%) had PDR. All 13 children harboured non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations, of whom seven also had nucleoside reverse transcriptase inhibitor resistance. After 24 months, 33% had experienced treatment failure. Treatment failure was associated with PDR and a higher log VL before treatment initiation (adjusted odds ratio (aOR) 7.53 (95%CI 1.61-35.15) and 2.85 (95%CI 1.04-7.78), respectively). DISCUSSION: PDR was present in one out of six Nigerian children. These high numbers corroborate with recent findings in other African countries. The presence of PDR was relevant as it was the strongest predictor of first-line treatment failure. CONCLUSIONS: Our findings stress the importance of implementing fully active regimens in children living with HIV. This includes the implementation of protease inhibitor (PI)-based first-line ART, as is recommended by the WHO for all HIV-infected children <3 years of age. Overcoming practical barriers to implement PI-based regimens is essential to ensure optimal treatment for HIV-infected children in sub-Saharan Africa. In countries where individual VL or resistance testing is not possible, more attention should be given to paediatric PDR surveys.

Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa.

BACKGROUND: As antiretroviral therapy (ART) programs in sub-Saharan Africa mature, increasing numbers of persons with human immunodeficiency virus (HIV) infection will experience treatment failure, and require second- or third-line ART. Data on second-line failure and development of protease inhibitor (PI) resistance in sub-Saharan Africa are scarce. METHODS: HIV-1-infected adults were included if they received >180 days of PI-based second-line ART. We assessed risk factors for having a detectable viral load (VL, ≥400 cps/mL) using Cox models. If VL was ≥1000 cps/mL, genotyping was performed. RESULTS: Of 227 included participants, 14.6%, 15.2% and 11.1% had VLs ≥400 cps/mL at 12, 24, and 36 months, respectively. Risk factors for a detectable VL were as follows: exposure to nonstandard nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based (hazard ratio, 7.10; 95% confidence interval, 3.40-14.83; P < .001) or PI-based (7.59; 3.02-19.07; P = .001) first-line regimen compared with zidovudine/lamivudine/NNRTI, PI resistance at switch (6.69; 2.49-17.98; P < .001), and suboptimal adherence (3.05; 1.71-5.42; P = .025). Among participants with VLs ≥1000 cps/mL, 22 of 32 (69%) harbored drug resistance mutation(s), and 7 of 32 (22%) harbored PI resistance. CONCLUSIONS: Although VL suppression rates were high, PI resistance was detected in 22% of participants with VLs ≥1000 cps/mL. To ensure long-term ART success, intensified support for adherence, VL and drug resistance testing, and third-line drugs will be necessary.

Accumulation of HIV-1 drug resistance after continued virological failure on first-line ART in adults and children in sub-Saharan Africa.

OBJECTIVES: Limited availability of viral load (VL) monitoring in HIV treatment programmes in sub-Saharan Africa can delay switching to second-line ART, leading to the accumulation of drug resistance mutations (DRMs). The objective of this study was to evaluate the accumulation of resistance to reverse transcriptase inhibitors after continued virological failure on first-line ART, among adults and children in sub-Saharan Africa. METHODS: HIV-1-positive adults and children on an NNRTI-based first-line ART were included. Retrospective VL and, if VL ≥1000 copies/mL, pol genotypic testing was performed. Among participants with continued virological failure (≥2 VL ≥1000 copies/mL), drug resistance was evaluated. RESULTS: At first virological failure, DRM(s) were detected in 87% of participants: K103N (38.7%), G190A (21.8%), Y181C (20.2%), V106M (8.4%), K101E (8.4%), any E138 (7.6%) and V108I (7.6%) associated with NNRTIs, and M184V (69.7%), any thymidine analogue mutation (9.2%), K65R (5.9%) and K70R (5.0%) associated with NRTIs. New DRMs accumulated with an average rate of 1.45 (SD 2.07) DRM per year; 0.62 (SD 1.11) NNRTI DRMs and 0.84 (SD 1.38) NRTI DRMs per year, respectively. The predicted susceptibility declined significantly after continued virological failure for all reverse transcriptase inhibitors (all P < 0.001). Acquired drug resistance patterns were similar in adults and children. CONCLUSIONS: Patterns of drug resistance after virological failure on first-line ART are similar in adults and children in sub-Saharan Africa. Improved VL monitoring to prevent accumulation of mutations, and new drug classes to construct fully active regimens, are required.

Estimating the Risk of ABO Hemolytic Disease of the Newborn in Lagos.

Background. ABO hemolytic disease of the newborn is the most common hemolytic consequence of maternofetal blood group incompatibility restricted mostly to non-group-O babies of group O mothers with immune anti-A or anti-B antibodies. Aim. We estimated the risk of ABO HDN with view to determining need for routine screening for ABO incompatibility between mother and fetus. Materials and Methods. Prevalence of ABO blood group phenotypes in blood donors at the donor clinic of the Lagos University Teaching Hospital and arithmetic methods were used to determine population prevalence of ABO genes. We then estimated proportion of pregnancies of group O mothers carrying a non-group-O baby and the risk that maternofetal ABO incompatibility will cause clinical ABO HDN. Results. Blood from 9138 donors was ABO typed. 54.3%, 23%, 19.4%, and 3.3% were blood groups O, A, B, and AB, respectively. Calculated gene frequencies were 0.1416, 0.1209, and 0.7375 for A, B, and O genes, respectively. It was estimated that 14.3% of deliveries will result in a blood group O woman giving birth to a child who is non-group-O. Approximately 4.3% of deliveries are likely to suffer ABO HDN with 2.7% prone to suffer from moderately severe to severe hemolysis.

Pretreatment HIV drug resistance increases regimen switches in sub-Saharan Africa.

BACKGROUND: After the scale-up of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection in Africa, increasing numbers of patients have pretreatment drug resistance. METHODS: In a large multicountry cohort of patients starting standard first-line ART in six African countries, pol genotyping was retrospectively performed if viral load (VL) ≥1000 cps/mL. Pretreatment drug resistance was defined as a decreased susceptibility to ≥1 prescribed drug. We assessed the effect of pretreatment drug resistance on all-cause mortality, new AIDS events and switch to second-line ART due to presumed treatment failure, using Cox models. RESULTS: Among 2579 participants for whom a pretreatment genotype was available, 5.5% had pretreatment drug resistance. Pretreatment drug resistance was associated with an increased risk of regimen switch (adjusted hazard ratio [aHR] 3.80; 95% confidence interval [CI], 1.49-9.68; P = .005) but was not associated with mortality (aHR 0.75, 95% CI, .24-2.35; P = .617) or new AIDS events (aHR 1.06, 95% CI, .68-1.64; P = .807). During three years of follow up, 106 (4.1%) participants switched to second-line, of whom 18 (17.0%) switched with VL < 1000 cps/mL, 7 (6.6%) with VL ≥ 1000 cps/mL and no drug resistance mutations (DRMs), 46 (43.4%) with VL ≥ 1000 cps/mL and ≥1 DRMs; no HIV RNA data was available for 32 (30.2%) participants. CONCLUSIONS: Given rising pretreatment HIV drug resistance levels in sub-Saharan Africa, these findings underscore the need for expanded access to second-line ART. VL monitoring can improve the accuracy of failure detection and efficiency of switching practices.