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PubMed | Duke University, University of Lagos, First Avenue Partners, Johns Hopkins University and Macaulay Institute
Type: | Journal: Journal of clinical microbiology | Year: 2016

The need to expand malaria diagnosis alongside policy requirements for mandatory testing before treatment motivates exploration of non-invasive rapid diagnostic tests (RDTs). We report the outcome of the first cross-sectional, single-blind clinical performance evaluation of a Urine Malaria Test (UMT) for Plasmodium falciparum (Pf) malaria diagnosis in febrile patients.Matched urine and fingerprick blood from participants 2 years with fever (axillary temperature 37.5C) or history of fever in the preceding 48 hours were tested with UMT and microscopy (as gold standard). BinaxNOW (Pf/Pan) blood RDT was done to assess relative performance. Urinalysis and Rheumatoid Factor (RF) tests were conducted to evaluate possible interference. Diagnostic performance characteristics were computed at 95% CI.Of 1,800 participants screened, 1,691 were enrolled; 566 (34%) were febrile, 1,125 (66%) afebrile; test positivity among enrolled participants: 341 (20%) by microscopy, 419 (25%) UMT, 676 (40%) BinaxNow Pf and 368 (22%) BinaxNow Pan. UMT sensitivity among febrile patients (for whom the test is indicated) was 85% and specificity 84%. Among febrile children 5 years, UMT sensitivity was 93%, specificity 83%. Area under receiver-operator characteristic curve (AUC) of UMT (0.84) was not significantly different from Binax Pf (0.86) or Binax Pan (0.87), indicating that the tests do not differ in overall performance. Gender, seasons, and RF did not impact UMT performance. Leukocytes, hematuria and urobilinogen concentration in urine were associated with lower UMT specificity.UMT performance was comparable to BinaxNOW Pf/Pan tests, and is a promising tool to expand malaria testing in public and private healthcare settings where there are challenges to blood-based malaria diagnosis testing.


PubMed | U.S. Army, Johns Hopkins University, University of Maryland, Baltimore, Population Council Nigeria and Institute of Human Virology Nigeria
Type: Journal Article | Journal: Journal of the International AIDS Society | Year: 2016

Sexually transmitted infection (STI) and HIV prevalence have been reported to be higher amongst men who have sex with men (MSM) in Nigeria than in the general population. The objective of this study was to characterize the prevalence of HIV, chlamydia and gonorrhoea in this population using laboratory-based universal testing.TRUST/RV368 represents a cohort of MSM and transgender women (TGW) recruited at trusted community centres in Abuja and Lagos, Nigeria, using respondent-driven sampling (RDS). Participants undergo a structured comprehensive assessment of HIV-related risks and screening for anorectal and urogenital From March 2013 to January 2016, 862 MSM and TGW (316 in Lagos and 546 in Abuja) underwent screening for HIV, chlamydia and gonorrhoea at study enrolment. Participants median age was 24 years [interquartile range (IQR) 21-27]. One-third (34.2%) were identified as gay/homosexual and 65.2% as bisexual. The overall prevalence of HIV was 54.9%. After adjusting for the RDS recruitment method, HIV prevalence in Abuja was 43.5% (95% CI 37.3-49.6%) and in Lagos was 65.6% (95% CI 54.7-76.5%). The RDS-weighted prevalence of chlamydia was 17.0% (95% CI 11.8-22.3%) in Abuja and 18.3% (95% CI 11.1-25.4%) in Lagos. Chlamydia infection was detected only at the anorectal site in 70.2% of cases. The RDS-weighted prevalence of gonorrhoea was 19.1% (95% CI 14.6-23.5%) in Abuja and 25.8% (95% CI 17.1-34.6%) in Lagos. Overall, 84.2% of gonorrhoea cases presented with anorectal infection only. Over 95% of STI cases were asymptomatic. In a multivariable model, increased risk for chlamydia/gonorrhoea was associated with younger age, gay/homosexual sexual orientation and higher number of partners for receptive anal sex. HIV infection was associated with older age, female gender identity and number of partners for receptive anal sex.There is a high burden of infection with HIV and asymptomatic chlamydia and gonorrhoea among MSM and TGW in Nigeria. Most cases would have been missed without anorectal screening. Interventions are needed to target this population for appropriate STI screening and management beginning at a young age.


Lihana R.W.,Kenya Medical Research Institute | Ssemwanga D.,MRC UVRI Uganda Research Unit on AIDS | Abimiku A.,University of Maryland Baltimore County | Abimiku A.,Institute of Human Virology Nigeria | Ndembi N.,University of Maryland Baltimore County
AIDS Reviews | Year: 2012

Background: HIV-1 strains have diversified extensively through mutation and recombination since their initial transmission to human beings many decades ago in Central Africa in the first part of the 20 th Century (between 1915 and 1941). The upward trend in global HIV-1 diversity has continued unabated, with newer groups, subtypes, and unique and circulating recombinants increasingly being reported, especially in Africa. Objective: In this review, we focus on the extensive diversity of HIV-1 over a decade (2000-2011), in 51 countries of the three African geographic regions (eastern and southern, western and central, and northern Africa) as per the WHO/UNAIDS 2010 classification. Methodology: References for this review were identified through searches of PubMed, conference abstracts, Google Scholar, and Springer Online Archives Collection. We retrieved 273 citations, of which 200 reported HIV-1 diversity from Africa from January, 2000 to August, 2011. Articles resulting from these searches and relevant references cited in those articles were reviewed. Articles published in English and French were included. Findings: There has been a high diversity of HIV-1 in its epicenter, west-central Africa. A few subtypes, namely, A (A1, A2, A3, A4, A5), C, CRF02-AG, and D accounted for about 85% of new infections. Subtype A and D have been stable in East Africa; C in southern Africa; A, G, CRF02-AG, and CRF06-cpx in western Africa; and subtype B and CRF02-AG in northern Africa. Recently a new putative group, designated P, was reported to be found in two Cameroonians. Conclusion: The regional distributions of individual subtypes and recombinants are broadly stable, although unique/circulating recombinant forms may play an increasing role in the HIV pandemic. Understanding the kinetics and directions of this continuing adaptation and its impact on viral fitness, immunogenicity, and pathogenicity are crucial to the successful design of effective HIV vaccines. There is need for regular monitoring and review updates, such as the one presented here, to assist countries to plan and anticipate complex forms that may be introduced with time.


Anude C.J.,University of Maryland Baltimore County | Anude C.J.,Johns Hopkins University | Eze E.,University of Benin | Onyegbutulem H.C.,Asokoro District Hospital | And 9 more authors.
BMC Infectious Diseases | Year: 2013

Background: Predictors of immuno-virologic outcomes and discordance and their associations with clinical, demographic, socio-economic and behavioral risk factors are not well described in Nigeria since HIV viral load testing is not routinely offered in public HIV treatment programs.Methods: The HACART study was a multi-center observational clinic-based cohort study of 2585 adults who started HAART between April 2008 and February 2009. A total of 628 patients were randomly selected at 12 months for immuno-virologic analyses.Results: Virologic suppression rate (<400 copies/ml) was 76.7%, immunologic recovery rate (CD4 change from baseline ≥50 cells/mm3) was 77.4% and immuno-virologic discordance rate was 33%. In multivariate logistic regression, virologic failure was associated with age <30 years (OR 1.79; 95% CI: 1.17-2.67, p=0.03), anemia (Hemoglobin < 10 g/dl) (OR 1.71; 95% CI: 1.22-2.61, p=0.03), poor adherence (OR 3.82; 95% CI: 2.17-5.97, p=0.001), and post-secondary education (OR 0.60; 95% CI: 0.30-0.86, p=0.02). Immunologic failure was associated with male gender (OR 1.46; 95% CI: 1.04-2.45, p=0.04), and age <30 years (OR 1.50; 95% CI: 1.11-2.39, p=0.03). Virologic failure with immunologic success (VL-/CD4+) was associated with anemia (OR 1.80; 95% CI: 1.13-2.88, p=0.03), poor adherence (OR 3.90; 95% CI: 1.92-8.24, p=0.001), and post-secondary education (OR 0.40; 95% CI: 0.22-0.68, p=0.005).Conclusions: Although favorable immuno-virologic outcomes could be achieved in this large ART program, immuno-virologic discordance was observed in a third of the patients. Focusing on intensified treatment preparation and adherence, young patients, males, persons with low educational status and most importantly baseline anemia assessment and management may help address predictors of poor immuno-virologic outcomes, and improve overall HIV program impact. Viral load testing in addition to the CD4 testing should be considered to identify, characterize and address negative immuno-virologic outcomes and discordance. © 2013 Anude et al; licensee BioMed Central Ltd.


PubMed | University of Amsterdam, Institute of Human Virology Nigeria and University of Lagos
Type: Journal Article | Journal: Journal of the International AIDS Society | Year: 2016

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.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 Of the total 82 PMTCT-nave 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).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.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.


PubMed | University of Minnesota, Virginia Commonwealth University, Asociacion Civil Impacta Salud y Educacion, University of New South Wales and 13 more.
Type: Journal Article | Journal: The Lancet. Respiratory medicine | Year: 2016

Observational data have been conflicted regarding the potential role of HIV antiretroviral therapy (ART) as a causative factor for, or protective factor against, COPD. We therefore aimed to investigate the effect of immediate versus deferred ART on decline in lung function in HIV-positive individuals.We did a nested substudy within the randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial at 80 sites in multiple settings in 20 high-income and low-to-middle-income countries. Participants were HIV-1 infected individuals aged at least 25 years, naive to ART, with CD4 T-cell counts of more than 500 per L, not receiving treatment for asthma, and without recent respiratory infections (baseline COPD was not an exclusion criterion). Participants were randomly assigned to receive ART (an approved drug combination derived from US Department of Health and Human Services guidelines) either immediately, or deferred until CD4 T-cell counts decreased to 350 per L or AIDS developed. The randomisation was determined by participation in the parent START study, and was not specific to the substudy. Because of the nature of our study, site investigators and participants were not masked to the treatment group assignment; however, the assessors who reviewed the outcomes were masked to the treatment group. The primary outcome was the annual rate of decline in lung function, expressed as the FEVBetween March 11, 2010, and Aug 23, 2013, we enrolled 1026 participants to our substudy, who were then randomly assigned to either immediate (n=518) or deferred (n=508) ART. Median baseline characteristics included age 36 years (IQR 30-44), CD4 T-cell count 648 per L (583-767), and HIV plasma viral load 42 logThe timing of ART initiation has no major short-term effect on rate of lung function decline in HIV-positive individuals who are naive to ART, with CD4 T-cell counts of more than 500 per L. In light of updated WHO recommendations that all HIV-positive individuals should be treated with ART, regardless of their CD4 T-cell count, our results suggest an absence of significant pulmonary harm with such an approach.US National Heart Lung and Blood Institute, US National Institute of Allergy and Infectious Diseases, Division of AIDS, Agence Nationale de Recherches sur le SIDA et les Hipatites Virales (France), Australian National Health and Medical Research Council, Danish National Research Foundation, European AIDS Treatment Network, German Ministry of Education and Research, UK Medical Research Council and National Institute for Health Research, and US Veterans Health Administration Office of Research and Development.


Sam-Agudu N.A.,Institute of Human Virology Nigeria | Cornelius L.J.,Institute of Human Virology Nigeria | Okundaye J.N.,Institute of Human Virology Nigeria | Adeyemi O.A.,Institute of Human Virology Nigeria | And 8 more authors.
Journal of acquired immune deficiency syndromes (1999) | Year: 2014

BACKGROUND: Nigeria is a key target country in the global effort toward elimination of mother-to-child transmission of HIV. Low coverage of prevention of mother-to-child transmission (PMTCT) interventions, adherence, and retention-in-care rates in HIV-positive pregnant women are contributing factors to high mother-to-child transmission of HIV (MTCT) rates. In Nigeria, rural areas, served largely by primary health care facilities, have particularly poor indicators of PMTCT coverage. Mentor Mothers are HIV-positive women who serve as peer counselors for PMTCT clients, provide guidance, and support in keeping appointments and promoting antiretroviral adherence and retention-in-care. The Mother Mentor (MoMent) study aims to investigate the impact of structured Mentor Mother programs on PMTCT outcomes in rural Nigeria.DESIGN AND METHODS: A prospective cohort study will compare rates of retention-in-care among PMTCT clients who are supported by formally-trained supervised Mentor Mothers versus clients who receive standard-of-care, informal peer support. Study sites are 20 primary health care centers (10 intervention, 10 control) in rural North-Central Nigeria. The study population is HIV-positive mothers and exposed infant pairs (MIPs) (N = 480; 240 MIPs per study arm). Primary outcome measures are the proportion of exposed infants receiving early HIV testing by age 2 months, and the proportion of MIPs retained in care at 6 months postpartum. Secondary outcome measures examine antiretroviral adherence, 12-month postpartum MIP retention, and MTCT rates. This article presents details of the study design, the structured Mentor Mother programs, and how their impact on PMTCT outcomes will be assessed.


Etiebet M.-A.A.,University of Maryland Baltimore County | Shepherd J.,University of Maryland Baltimore County | Nowak R.G.,University of Maryland Baltimore County | Charurat M.,University of Maryland Baltimore County | And 8 more authors.
AIDS | Year: 2013

BACKGROUND: In resource-limited settings, HIV-1 drug resistance testing to guide antiretroviral therapy (ART) selection is unavailable. We retrospectively conducted genotypic analysis on archived samples from Nigerian patients who received targeted viral load testing to confirm treatment failure and report their drug resistance mutation patterns. METHODS: Stored plasma from 349 adult patients on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens was assayed for HIV-1 RNA viral load, and samples with more than 1000copies/ml were sequenced in the pol gene. Analysis for resistance mutations utilized the IAS-US 2011 Drug Resistance Mutation list. RESULTS: One hundred and seventy-five samples were genotyped; the majority of the subtypes were G (42.9%) and CRF02-AG (33.7%). Patients were on ART for a median of 27 months. 90% had the M184V/I mutation, 62% had at least one thymidine analog mutation, and 14% had the K65R mutation. 97% had an NNRTI resistance mutation and 47% had at least two etravirine-associated mutations. In multivariate analysis tenofovir-based regimens were less likely to have at least three nucleoside reverse transcriptase inhibitor (NRTI) mutations after adjusting for subtype, previous ART, CD4, and HIV viral load [P<0.001, odds ratio (OR) 0.04]. 70% of patients on tenofovir-based regimens had at least two susceptible NRTIs to include in a second-line regimen compared with 40% on zidovudine-based regimens (P=0.04, OR=3.4). CONCLUSIONS: At recognition of treatment failure, patients on tenofovir-based first-line regimens had fewer NRTI drug-resistant mutations and more active NRTI drugs available for second-line regimens. These findings can inform strategies for ART regimen sequencing to optimize long-term HIV treatment outcomes in low-resource settings. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Charurat M.E.,University of Maryland Baltimore County | Emmanuel B.,University of Maryland Baltimore County | Akolo C.,University of Maryland Baltimore County | Akolo C.,Institute of Human Virology Nigeria | And 8 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2015

Background: Experimental evidence has shown that treatment of HIV infection with antiretroviral therapy (ART) prevents heterosexual transmission of HIV to an uninfected partner. However, the "real-world" application of this strategy to key populations such as menwho have sex with men (MSM) has been limited. We report findings on acceptability of a treatment as prevention (TasP) strategy among HIV-infected MSM at a Trusted Community Center providing comprehensive HIV prevention and treatment services to MSM in Abuja, Nigeria. Methods: Using respondent-driven sampling (RDS), MSM who were 16 years and older and have engaged in either receptive or insertive anal intercourse within the previous 12 months were recruited into a prospective combination HIV prevention and treatment study (TRUST). Two weeks after enrollment, HIV testing and counseling was conducted. At each 3-month follow-up visits, HIV-infected individuals underwent clinical and laboratory evaluation, including CD4 count, plasma HIV viral load, immediate 3 weekly sessions of ART preparation, and then ART initiation per TasP strategy irrespective of CD4 count. Reasons for not engaging in pre-TasP preparation and TasP were documented. Characteristics associated with TasP engagement and loss to follow-up (LTFU) were determined using logistic and Cox regression, respectively. Results: Of 186 HIV-positive MSM enrolled, 58 (31.2%) were on ART at the time of recruitment, whereas 128 (68.8%) were ART-naive and provided opportunity for engaging TasP. Of these, 70 (54.7%) engaged in TasP. Compared with MSM who did not engage in TasP, those who engaged had significantly lower mean CD4 count (P = 0.001), were more likely to be Christian (P = 0.01), and had disclosed being MSM to family (P = 0.02) or health care providers (P = 0.02). In multivariate models, disclosure of being MSM to health care providers remained significantly associated with uptake of TasP. Among individuals engaged in TasP, 10% were LTFU in care at 18 months since enrollment. Being engaged in TasP (relative hazards = 0.08, P < 0.001) and on ART (relative hazards = 0.17, P < 0.001) were associated with decreased risk of LTFU. Conclusions: Although there was high acceptance of HIV testing and low LTFU among individuals who were already on ART or engaged in TasP, a higher than expected proportion did not engage in TasP, suggesting the need for customized treatment preparation and an increase in enabling environments to support HIV treatment access with this key population. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


PubMed | Institute of Human Virology Nigeria, Obafemi Awolowo University and University of Nevada, Las Vegas
Type: Journal Article | Journal: Pediatric research | Year: 2016

More than 80% of the HIV-infected adolescents live in sub-Saharan Africa. Acquired immune deficiency syndrome (AIDS)-related mortality has increased among adolescents 10-19 y old. The impact is highest in sub-Saharan Africa, where >80% of HIV-infected adolescents live. The World Health Organization has cited inadequate access to HIV testing and counseling (HTC) as a contributing factor to AIDS-related adolescent deaths, most of which occur in sub-Saharan Africa. This review focuses on studies conducted in high adolescent HIV-burden countries targeted by the All In to End Adolescent AIDS initiative, and describes barriers to adolescent HTC uptake and coverage. Fear of stigma and family reaction, fear of the impact of a positive diagnosis, perceived risk with respect to sexual exposure, poor attitudes of healthcare providers, and parental consent requirements are identified as major impediments. Most-at-risk adolescents for HIV infection and missed opportunities for testing include, those perinatally infected, those with early sexual debut, high mobility and multiple/older partners, and pregnant and nonpregnant females. Regional analyses show relatively low adolescent testing rates and more restrictive consent requirements for HTC in West and Central Africa as compared to East and southern Africa. Actionable recommendations for widening adolescent access to HTC and therefore timely care include minimizing legal consent barriers, healthcare provider training, parental education and involvement, and expanding testing beyond healthcare facilities.

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