Publications by authors named "Babafemi O Taiwo"

42 Publications

Effect of Text Messaging Plus Peer Navigation on Viral Suppression Among Youth With HIV in the iCARE Nigeria Pilot Study.

J Acquir Immune Defic Syndr 2021 Aug;87(4):1086-1092

Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL.

Background: Consistent with the global trend, youth with HIV (YWH) in Nigeria have high rates of viral nonsuppression. Hence, novel interventions are needed.

Setting: Infectious Diseases Institute, College of Medicine, University of Ibadan, Nigeria.

Methods: In a single-arm trial, participants aged 15-24 years received 48 weeks of a combination intervention, comprising daily 2-way text message medication reminders plus peer navigation. The primary outcome measure was viral suppression less than 200 copies/mL. The secondary outcome measures included self-reported adherence on a visual analog scale and medication possession ratio, each dichotomized as ≥90% (good) or <90% (poor) adherence. The outcomes were analyzed using McNemar test. Retention in care, intervention feasibility and acceptability, and participants' satisfaction were also assessed.

Results: Forty YWH (50% male participants) were enrolled: mean age 19.9 years (SD = 2.5), 55% perinatally infected, and 35% virologically suppressed at baseline. Compared with baseline, the odds of virologic suppression was higher at 24 weeks (odds ratio = 14.00, P < 0.001) and 48 weeks (odds ratio = 6.00, P = 0.013). Self-reported adherence (≥90%) increased from baseline at 24 weeks (63%, P = 0.008) and 48 weeks (68%, P = 0.031). Medication possession ratio ≥90% increased at weeks 24 and 48 (85% and 80%, respectively), achieving statistical significance at 24 weeks alone (P = 0.022). Retention in care at 48 weeks was 87.5%. All (37/37) participants at week 48 were fully or mostly satisfied with the intervention.

Conclusion: Daily 2-way text message reminders plus peer navigation is a promising combination intervention to improve viral suppression among YWH in Nigeria.
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http://dx.doi.org/10.1097/QAI.0000000000002694DOI Listing
August 2021

Coincident rapid expansion of two SARS-CoV-2 lineages with enhanced infectivity in Nigeria.

medRxiv 2021 Jul 2. Epub 2021 Jul 2.

Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

The emergence of new SARS-CoV-2 variants with enhanced transmissibility or decreased susceptibility to immune responses is a major threat to global efforts to end the coronavirus disease 2019 (COVID-19) pandemic. Disparities in viral genomic surveillance capabilities and efforts have resulted in gaps in our understanding of the viral population dynamics across the globe. Nigeria, despite having the largest population of any nation in Africa, has had relatively little SARS-CoV-2 sequence data made publicly available. Here we report the whole-genome sequences of 74 SARS-CoV-2 isolates collected from individuals in Oyo State, Nigeria in January 2021. Most isolates belonged to either the B.1.1.7 Alpha "variant of concern" or the B.1.525 Eta lineage, which is currently considered a "variant of interest" containing multiple spike protein mutations previously associated with enhanced transmissibility and possible immune escape. Nigeria has the highest reported frequency of the B.1.525 lineage globally with phylogenetic characteristics consistent with a recent monophyletic origin and rapid expansion. Spike protein from the B.1.525 lineage displayed both increased infectivity and decreased neutralization by convalescent sera compared to Spike proteins from other clades. These results, along with indications that the virus is outpacing the B.1.1.7 lineage in Nigeria, suggest that the B.1.525 lineage represents another "variant of concern" and further underline the importance of genomic surveillance in undersampled regions across the globe.
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http://dx.doi.org/10.1101/2021.04.09.21255206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057251PMC
July 2021

Interactions between helminths and tuberculosis infections: Implications for tuberculosis diagnosis and vaccination in Africa.

PLoS Negl Trop Dis 2020 06 4;14(6):e0008069. Epub 2020 Jun 4.

TB Research Group, Animal and Plant Health Agency, Surrey, United Kingdom.

Africa is the second most populous continent and has perennial health challenges. Of the estimated 181 million school aged children in sub-Saharan Africa (SSA), nearly half suffer from ascariasis, trichuriasis, or a combination of these infections. Coupled with these is the problem of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection, which is a leading cause of death in the region. Compared to the effect of the human immunodeficiency virus on the development of TB, the effect of chronic helminth infections is a neglected area of research, yet helminth infections are as ubiquitous as they are varied and may potentially have profound effects upon host immunity, particularly as it relates to TB infection, diagnosis, and vaccination. Protection against active TB is known to require a clearly delineated T-helper type 1 (Th1) response, while helminths induce a strong opposing Th2 and immune-regulatory host response. This Review highlights the potential challenges of helminth-TB co-infection in Africa and the need for further research.
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http://dx.doi.org/10.1371/journal.pntd.0008069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272205PMC
June 2020

Differential Associations of Chronic Inflammatory Diseases With Incident Heart Failure.

JACC Heart Fail 2020 06 8;8(6):489-498. Epub 2020 Apr 8.

Division of Cardiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. Electronic address:

Objectives: The purpose of this study was to compare the risks of incident heart failure (HF) among a variety of chronic inflammatory diseases (CIDs) and to determine whether risks varied by severity of inflammation within each CID.

Background: Individuals with CIDs are at elevated risk for cardiovascular diseases, but data are limited regarding risk for HF.

Methods: An electronic health records database from a large urban medical system was examined, comparing individuals with CIDs with frequency-matched controls without CIDs, all of whom were receiving regular outpatient care. Rates of incident HF were determined by using the Kaplan-Meier method and subsequently used multivariate-adjusted proportional hazards models to compare HF risks for each CID. Exploratory analyses determined HF risks by proxy measurement of CID severity.

Results: Of 37,636 patients (n = 18,278 patients with CIDs; and n = 19,358 controls without CIDs) there were 960 incident HF cases over a median of 3.6 years. Risks for incident HF were significantly or borderline significantly elevated for patients with systemic sclerosis (hazard ratio [HR]: 7.26; 95% confidence interval [CI]: 5.72 to 9.21; p < 0.01), systemic lupus erythematosus (HR: 3.15; 95% CI: 2.41 to 4.11; p < 0.01), rheumatoid arthritis (HR: 1.39; 95% CI: 1.13 to 1.71; p < 0.01), and human immunodeficiency virus (HR: 1.28; 95% CI: 0.99 to 1.66; p = 0.06). There was no association between psoriasis or inflammatory bowel disease and incident HF, although patients with those CIDs with higher levels of C-reactive protein had higher risks for HF than controls.

Conclusions: Systemic sclerosis and systemic lupus erythematosus were associated with the highest risks of HF, followed by rheumatoid arthritis and HIV. Measurements of inflammation were associated with HF risk across different CIDs.
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http://dx.doi.org/10.1016/j.jchf.2019.11.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261254PMC
June 2020

Limited correlation between systemic biomarkers and neurocognitive performance before and during HIV treatment.

J Neurovirol 2020 02 29;26(1):107-113. Epub 2019 Aug 29.

Division of Infectious Diseases, Northwestern Univeristy, 645 N. Michigan Avenue, Suite 900, Chicago, IL, 60611, USA.

The AIDS Clinical Trials Group (ACTG) study A5303 investigated the associations between neuropsychological performance (NP) and inflammatory biomarkers in HIV-infected participants. Fifteen NP tests were administered at baseline and week 48 to 233 ART naïve participants randomized to maraviroc- or tenofovir-containing ART. Neurocognition correlated modestly with markers of lymphocyte activation and inflammation pre-ART (percent CD38+/HLA-DR+(CD4+) (r = - 0.22, p = 0.02) and percent CD38+/HLA-DR+(CD8+) (r = - 0.25, p = 0.02)), and with some monocyte subsets during ART (r = 0.25, p = 0.02). Higher interleukin-6 and percent CD38+/HLA-DR+(CD8+) were independently associated with worse severity of HIV-associated neurocognitive disorders (HAND) (p = 0.04 and 0.01, respectively). More studies to identify HAND biomarkers are needed.
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http://dx.doi.org/10.1007/s13365-019-00795-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044026PMC
February 2020

Initial Antiretroviral Therapy in an Integrase Inhibitor Era: Can We Do Better?

Infect Dis Clin North Am 2019 09 22;33(3):681-692. Epub 2019 Jun 22.

Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, 645 North Michigan Avenue, Suite 900, Chicago, IL 60611, USA.

With the second-generation integrase inhibitors (dolutegravir and bictegravir) extending the attributes of earlier integrase inhibitors, three-drug regimens containing integrase inhibitors plus two nucleos(t)ide reverse transcriptase inhibitors are now widely recommended for first-line (initial) treatment of human immunodeficiency virus-1 infection. Led by dolutegravir plus lamivudine, two-drug therapy is emerging as a way to reduce antiretroviral therapy cost and adverse effects without compromising treatment options should virologic failure occur. Initial two-drug therapy has limitations, including the relative incompatibility with the coemerging concept of same-day antiretroviral therapy initiation.
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http://dx.doi.org/10.1016/j.idc.2019.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178329PMC
September 2019

Successful treatment of a intra-articular infection.

Emerg Microbes Infect 2019 ;8(1):866-868

a Division of Infectious Diseases , Northwestern University Feinberg School of Medicine , Chicago , IL , USA.

A 78-year-old woman with a long-term ankle spacer with antibacterials developed an intra-articular infection. Treatment with systemic antifungal therapy plus an amphotericin B moulded cement spacer was successful.
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http://dx.doi.org/10.1080/22221751.2019.1625287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566482PMC
September 2019

Rapid HIV Antigen-Antibody Assays and Detection of Acute HIV Infection in Sub-Saharan Africa.

Am J Trop Med Hyg 2019 08;101(2):285-286

Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Detection of acute HIV infection is a unique problem that fourth-generation HIV assays were expected to alleviate. In this commentary, we draw attention to the limitations and challenges with use of currently available rapid antigen-antibody (Ag/Ab) combination tests for detection of acute HIV infection in sub-Saharan Africa. Laboratory-based HIV-1 Ag/Ab immunoassays are complex, requiring specialized equipment and handling that are currently not affordable in many settings in Africa. The point-of-care Ag/Ab platform on the other hand is easier to deploy and potentially more accessible in resource-limited settings. However, available fourth-generation HIV-1 rapid diagnostic tests have demonstrated poor performance characteristics in field studies where non-B subtypes of HIV-1 dominate. The potential for point-of-care HIV-1 Ag/Ab diagnostics to significantly improve detection of acute HIV infection remains yet to be realized in sub-Saharan Africa. Assay platforms need to be optimized to identify local circulating subtypes, and optimal algorithms need to be determined.
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http://dx.doi.org/10.4269/ajtmh.19-0144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685562PMC
August 2019

Willingness to Donate Hair Samples for Research Among People Living with HIV/AIDS Attending a Tertiary Health Facility in Ibadan, Nigeria.

AIDS Res Hum Retroviruses 2019 07 29;35(7):642-648. Epub 2019 May 29.

5 Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, San Francisco, California.

The use of hair samples in biomedical research is a rapidly growing field. High acceptability rates for hair collection have been demonstrated in multiple settings. Each setting may have unique issues and, to our knowledge, no previous study has assessed the acceptability of hair sampling for HIV-related research in Nigeria. This study aimed to assess the willingness to donate hair for research among people living with HIV (PLWH). A cross-sectional study was conducted among 381 PLWH in a tertiary institution in Southwest Nigeria, using convenience sampling. An interviewer-administered questionnaire was used to collect data from consenting participants, including a question on willingness to donate hair for research. The mean age of respondents was 42.1 ± 10.5 years and more than three-quarters of the respondents were females. Two hundred and eighty-eight (75.8%) respondents had at least a tertiary education. Only 51.4% of the respondents were willing to donate their hair for research. Possible sample diversion for rituals was the major (60.5%) reason cited for unwillingness to donate hair. In multivariate analysis, respondents with primary education or less exhibited a trend toward being more willing to donate hair than those with secondary education or more ( = .091). Muslims were 1.7 times more willing to donate hair than Christians even after adjusting for other demographic covariates (95% confidence interval: 1.11-2.72);  = .016. There is a moderate willingness to donate hair for research among our population of PLWH in Nigeria. These results underscore the importance of cultural sensitivity and community education when introducing innovative HIV research techniques to new settings.
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http://dx.doi.org/10.1089/AID.2018.0242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602105PMC
July 2019

Plasma Cystatin C Associates With HIV-Associated Neurocognitive Disorder but Is a Poor Diagnostic Marker in Antiretroviral Therapy-Treated Individuals.

J Acquir Immune Defic Syndr 2019 06;81(2):e49-e54

Division of Infectious Diseases, Department of Medicine, Northwestern University School of Medicine, Chicago, IL.

Objective: To examine associations between plasma cystatin C and neurocognitive impairment (NCI) and its performance as a diagnostic marker before and during initial antiretroviral therapy (ART).

Methods: Multivariable logistic regression and generalized estimating equations examined associations with NCI, determined by neuropsychological measurements, in participants of a 48-week randomized clinical trial of initial ART. Receiver operator characteristic curves examined diagnostic models of NCI.

Results: Cystatin C was associated with NCI before ART [odds ratio (OR) 3.4 (95% CI: 1.2 to 9.4) for each 2-fold increase in baseline levels] and during 48 weeks of ART, in models that excluded baseline measurements [OR 3.0 (1.2 to 7.8) for each 2-fold increase in time-updated levels]. The strength of association increased with more severe impairment using HIV-associated neurocognitive disorder criteria [OR 2.2 (0.8 to 6.0) with asymptomatic NCI and OR 4.0 (1.5 to 11.0) with mild neurocognitive disorder or HIV-associated dementia vs. no impairment, for each 2-fold increase in time-updated levels] or by global development score [OR 2.6 (1.1 to 6.3) with mild impairment and OR 4.6 (1.1 to 18.9) with moderate or severe impairment vs. no impairment]. Cystatin C performed poorly as a diagnostic marker for NCI, however, with an area under the receiver operator characteristic curve of 0.58 at baseline and 0.54 at week 48.

Conclusions: Higher plasma cystatin C levels were significantly associated with NCI, but these levels did not seem to be useful as a diagnostic marker for this condition.
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http://dx.doi.org/10.1097/QAI.0000000000002016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546291PMC
June 2019

No Significant Changes to Residual Viremia After Switch to Dolutegravir and Lamivudine in a Randomized Trial.

Open Forum Infect Dis 2019 Mar 11;6(3):ofz056. Epub 2019 Feb 11.

Division of Infectious Diseases, Northwestern University, Chicago, Illinois.

In the ASPIRE trial, antiretroviral therapy (ART) switch to dolutegravir plus lamivudine (DTG+3TC) was comparable to 3-drug ART in maintaining viral suppression by standard viral load assays. We used an ultrasensitive assay to assess whether this switch led to increased residual viremia. At entry, levels of residual viremia did not differ significantly between arms (DTG+3TC vs 3-drug ART: mean, 5.0 vs 4.2 HIV-1 RNA copies/mL; = .64). After randomization, no significant between-group differences were found at either week 24 or 48. These results show no evidence for increased viral replication on DTG+3TC and support its further investigation as a dual ART strategy.
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http://dx.doi.org/10.1093/ofid/ofz056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419983PMC
March 2019

Dolutegravir plus lamivudine for initial treatment of HIV-1-infected participants with HIV-1 RNA <500 000 copies/mL: week 48 outcomes from ACTG 5353.

J Antimicrob Chemother 2019 05;74(5):1376-1380

Northwestern University, Chicago, IL, USA.

Background: The AIDS Clinical Trials Group study A5353 demonstrated the efficacy and safety of dolutegravir and lamivudine for initial treatment of HIV-1 infection at week 24 in individuals with HIV-1 RNA 1000-500 000 copies/mL. Optimal ART for treatment-naive individuals must be durable.

Objectives: The aim of this study was to estimate the efficacy and safety of dolutegravir plus lamivudine at week 48 and compare the efficacy in participants with baseline HIV-1 RNA ≤100 000 copies/mL versus >100 000 copies/mL.

Methods: Virological success was defined as HIV-1 RNA <50 copies/mL by FDA Snapshot criteria. Definition of virological failure included confirmed HIV-1 RNA >200 copies/mL at week 24 or later. The proportion of participants with virological success was estimated using two-sided exact Clopper-Pearson 95% CI. Comparison between screening HIV-1 RNA (≤100 000 versus >100 000 copies/mL) strata was carried out by Fisher's exact test. The study was registered with ClinicalTrials.gov, number NCT02582684.

Results: A total of 120 enrolled eligible participants were included in the analysis. At week 48, 102 of the 120 participants (85%; 95% CI 77%-91%) had virological success. Virological success was similar between screening HIV-1 RNA groups. Six (5%) participants had virological non-success and one additional participant experienced virological failure while on study but off study treatment. No new drug resistance mutations were observed. Six (5%) participants had study-related grade 3 or higher adverse events and none discontinued study treatment.

Conclusions: These results add to the evidence that dolutegravir plus lamivudine is a safe and effective option for initial ART in individuals with HIV-1 RNA <500 000 copies/mL.
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http://dx.doi.org/10.1093/jac/dky564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477973PMC
May 2019

Physical Activity Is Associated With Lower Odds of Cognitive Impairment in Women but Not Men Living With Human Immunodeficiency Virus Infection.

J Infect Dis 2019 01;219(2):264-274

Division of Infectious Diseases and Center for Global Health.

Background: Cardiovascular comorbidities are risk factors for human immunodeficiency virus (HIV)-associated cognitive impairment. Given differences in cardiometabolic risk profiles between women and men with HIV, we investigated whether associations between cardiometabolic risk factors and prevalent cognitive impairment differ by sex.

Methods: Separate logistic regression models were constructed for women and men at entry into a prospective study of older persons with HIV (PWH) to assess the association of cardiometabolic and other risk factors with cognitive impairment.

Results: Of 988 participants, 20% were women. Women had higher total cholesterol (194 vs 186 mg/dL; P = .027), hemoglobin A1c (5.9% vs 5.7%; P = .003), and body mass index (30.8 vs 27.4 kg/m2; P < .001) compared with men, and were less physically active (43% vs 55%; P = .005). In a multivariable model, physical activity was associated with lower odds of cognitive impairment in women (odds ratio, 0.35 [95% confidence interval, .15-.80]; P = .013) but not men.

Conclusions: Physical activity may have a greater positive impact on cognitive health in women than in men with HIV. This finding should be confirmed in studies examining the longitudinal association between physical activity and incident cognitive impairment in PWH and the effect of interventions that increase physical activity on cognitive impairment in women with HIV.
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http://dx.doi.org/10.1093/infdis/jiy503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306019PMC
January 2019

Women have enhanced bone loss associated with phosphaturia and CD4+ cell restoration during initial antiretroviral therapy.

AIDS 2018 11;32(17):2517-2524

Division of Infectious Diseases, Northwestern University, Chicago, Illinois, USA.

Objective: We compared bone mineral density (BMD) changes and their correlates, between men and women participating in two randomized trials of initial [antiretroviral therapy (ART)] regimens, with or without tenofovir disoproxil fumarate (TDF).

Methods: Covariates in linear regression models of 48-week hip and spine %BMD changes, by dual energy X-ray absorptiometry, included baseline and 48-week changes in plasma viral load, CD4 cells, plasma C-terminal telopeptide, procollagen 1 N-terminal propeptide and glomerular filtration rates, and the 48-week area under the curve of fractional excretion of phosphate.

Results: Despite overall hip and spine BMD declines of 2.8 and 2.9%, respectively, plasma viral load suppression to less than 50 vs. at least 50 copies/ml was associated 1.0% (P = 0.02) and 0.8% (P = 0.01) less BMD decline. Women had lower baseline spine (P = 0.04; n = 59 women, 418 men) and hip BMD (P = 0.01) in adjusted models, with 1.7% more hip decline on ART than men (P = 0.001). Serum phosphate was positively associated with baseline spine BMD in women (P = 0.03) but not men, and area under the curve of fractional excretion of phosphate was negatively associated with spine BMD changes, particularly in women randomized to TDF regimens (P = 0.03 and 0.054 for interactions by sex, and randomization to TDF vs. non-TDF regimens, respectively; n = 44 women, 326 men). Women also had 0.6% (P = 0.004) more hip BMD decline than men associated with each 100 CD4 cells/μl increase on ART (P = 0.02; n = 49 women, 379 men).

Conclusion: Women randomized to TDF-containing ART had accentuated spine loss associated with phosphaturia, and accentuated hip loss associated with CD4 restoration, regardless of TDF exposure. Viral load suppression reduced bone loss.
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http://dx.doi.org/10.1097/QAD.0000000000001995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230267PMC
November 2018

ACTG A5353: A Pilot Study of Dolutegravir Plus Lamivudine for Initial Treatment of Human Immunodeficiency Virus-1 (HIV-1)-infected Participants With HIV-1 RNA <500000 Copies/mL.

Clin Infect Dis 2018 05;66(11):1689-1697

Division of Infectious Diseases, Weill Cornell Medicine, New York, New York.

Background: Limited data exist on initial human immunodeficiency virus type 1 (HIV-1) treatment with dolutegravir plus lamivudine.

Methods: A5353 is a phase 2, single-arm, pilot study of once-daily dolutegravir (50 mg) plus lamivudine (300 mg) in treatment-naive participants with HIV-1 RNA ≥1000 and <500000 copies/mL. Exclusion criteria included active hepatitis B or major protease, reverse transcriptase, or integrase resistance. The primary efficacy measure was the proportion with HIV-1 RNA <50 copies/mL (FDA [US Food and Drug Administration] Snapshot) at week 24. Virologic failure (VF) was confirmed HIV-1 RNA >400 copies/mL at week 16/20 or >200 copies/mL at or after week 24. Dolutegravir levels and drug resistance testing were performed at VF.

Results: One hundred and twenty participants (87% male, median age 30 years, 37 (31%) HIV-1 RNA >100000 copies/mL) initiated study treatment. Median entry HIV-1 RNA and CD4 count were 4.61 log10 copies/mL and 387 cells/mm3. Virologic efficacy at week 24 was 108/120 (90%, confidence interval [83%, 95%]), with comparable results in the >100000 copies/mL and ≤100000 copies/mL strata, that is, 89% (75%, 97%) and 90% (82%, 96%), respectively. Three participants with VF, had undetected plasma dolutegravir at ≥1 time points; the M184V and R263R/K mutations developed in 1 participant. Two participants experienced grade 3 possible/probable treatment-related adverse events; none discontinued treatment due to adverse events.

Conclusions: Dolutegravir plus lamivudine demonstrated efficacy in individuals with pretreatment HIV-1 RNA up to 500000 copies/mL in this pilot trial, but a participant developed resistance mutations.

Clinical Trials Registration: NCT02582684.
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http://dx.doi.org/10.1093/cid/cix1083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5961075PMC
May 2018

Statin Prescribing Practices in the Comprehensive Care for HIV-Infected Patients.

J Acquir Immune Defic Syndr 2017 09;76(1):e26-e29

*Division of Infectious Diseases, Northwestern University, Chicago, IL †Division of Infectious Diseases, Vanderbilt University, Nashville, TN ‡Division of Infectious Diseases, NorthShore University HealthSystem, Evanston, IL §Division of Cardiology, Northwestern University, Chicago, IL.

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http://dx.doi.org/10.1097/QAI.0000000000001454DOI Listing
September 2017

Long-Acting Antiretrovirals: Where Are We now?

Curr HIV/AIDS Rep 2017 04;14(2):63-71

Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine & Center for Global Health, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Purpose Of Review: Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals.

Recent Findings: Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development. Long-acting modalities in earlier development stages employ drug-loaded implants, microparticles, or targeted mutagenesis, among other innovations. Long-acting antiretroviral drugs promise new options for HIV prevention and treatment, and ways to address poor adherence and treatment fatigue. Further studies will identify the long-acting agents or combinations that are suitable for routine use. Creative solutions will be needed for anticipated implementation challenges.
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http://dx.doi.org/10.1007/s11904-017-0353-0DOI Listing
April 2017

Mobile phone use for a social strategy to improve antiretroviral refill experience at a low-resource HIV clinic: patient responses from Nigeria.

AIDS Care 2017 05 15;29(5):575-578. Epub 2016 Sep 15.

f Division of Infectious Diseases, Feinberg School of Medicine , Northwestern University , Chicago , USA.

In sub-Saharan African areas where antiretroviral (ARV) drugs are not available through community pharmacies, clinic-based pharmacies are often the primary source of ARV drug refills. Social pressure is mounting on treatment providers to adjust ARV refill services towards user-friendly approaches which prioritize patients' convenience and engage their resourcefulness. By this demand, patients may be signalling dissatisfaction with the current provider-led model of monthly visits to facility-based pharmacies for ARV refill. Mobile phones are increasingly popular in sub-Saharan Africa, and have been used to support ARV treatment goals in this setting. A patient-centred response to on-going social pressure requires treatment providers to view ARV refill activities through the eyes of patients who are negotiating the challenges of day-to-day life while contemplating their next refill appointment. Using focus groups of five categories of adult patients receiving combination ARV therapy, we conducted this cross-sectional qualitative study to provide insight into modifiable gaps between patients' expectations and experiences of the use of mobile phones in facility-based ARV refill service at a public HIV clinic in Nigeria. A notable finding was patients' preference for harnessing informal social support (through intermediaries with mobile phones) to maintain adherence to ARV refill appointments when they could not present in person. This evolving social support strategy also has the potential to enhance defaulter tracking. Our study findings may inform the development of ARV refill strategies and the design of future qualitative studies on client-provider communication by mobile phones in under-resourced HIV treatment programmes.
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http://dx.doi.org/10.1080/09540121.2016.1226476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5550104PMC
May 2017

Neurocognition with maraviroc compared with tenofovir in HIV.

AIDS 2016 09;30(15):2315-21

aUniversity of North Carolina at Chapel Hill, Chapel Hill, North Carolina bHarvard University, Boston, Massachusetts cJohns Hopkins Hospital, Baltimore, Maryland dNorthwestern University, Chicago, Illinois eFrontier Science & Technology, Amherst, New York, USA.

Objective: The objective was to determine whether maraviroc (MVC) has unique neurocognitive benefits in the context of initial antiretroviral therapy (ART).

Design: Randomized, double-blind, placebo-controlled, 48-week trial.

Setting: Participants were enrolled in US AIDS Clinical Trials Group clinical trial sites.

Participants: Total 262 ART-naive, chemokine coreceptor 5 tropic HIV, and HIV RNA greater than 1000 copies/ml participants were randomized, 230 participants completed the study.

Intervention: Participants received MVC 150 mg or tenofovir disoproxil fumarate (TDF) 300 mg on a background of ritonavir-boosted darunavir and emtricitabine.

Main Outcome Measure(s): The neuropsychological battery of 15 tests done at baseline, week 24 and week 48 assessed seven domains, and were standardized into z-scores then converted into deficit scores and a global deficit score. The 48-week changes from baseline in the neuropsychological scores and the global deficit score were compared by Wilcoxon or Kruskal-Wallis test between arms, and among baseline impairment groups [classified as normal, mild (2 deficit scores ≥1) and moderate (2 deficit scores ≥2)]. It was hypothesized that the MVC arm would have improved neuropsychological performance over TDF.

Results: In this double-blind, randomized, placebo-controlled trial, there were no differences in neuropsychological performance between MVC and TDF. Those with moderate neuropsychological impairment at baseline experienced greater ART-mediated neuropsychological improvement than those with mild or no neuropsychological impairment.

Conclusion: Improvement in neurocognitive functioning was greater with more baseline impairment but was comparable with MVC or TDF.
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http://dx.doi.org/10.1097/QAD.0000000000001189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5014739PMC
September 2016

Differential CD4+ cell count increase and CD4+ :  CD8+ ratio normalization with maraviroc compared with tenofovir.

AIDS 2016 08;30(13):2091-7

aStatistical and Data Analysis Center, Harvard Chan School of Public Health, Boston, Massachusetts bDepartment of Immunology and Microbiology, Rush University Medical Center, Chicago, Illinois cDivision of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University, Baltimore, Maryland dDivision of Infectious Diseases eDivision of Endocrinology and Metabolism and Lipids, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia fHIV Research Branch, Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland gDivision of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina hDivision of Infectious Diseases, University of Cincinnati, Cincinnati, Ohio iDivision of Infectious Diseases, Northwestern University, Chicago, Illinois, USA.

Objective: Studies exploring the immunologic effects of maraviroc (MVC) have produced mixed results; hence, it remains unclear whether MVC has unique immunologic effects in comparison with other antiretroviral drugs. We sought to determine whether MVC has differential effects compared with tenofovir disoproxil fumarate (TDF) during initial antiretroviral therapy.

Design: Prospective study in AIDS Clinical Trials Group A5303, a double-blind, placebo-controlled trial (N = 262) of MVC vs. TDF, each combined with boosted darunavir and emtricitabine.

Methods: A total of 31 cellular and soluble biomarkers were assayed at weeks 0 and 48. Polychromatic flow cytometry was performed on cryopreserved peripheral blood mononuclear cells. Soluble markers were assayed in plasma using ELISA kits. Analyses were as treated.

Results: Analyses included 230 participants (119 in MVC arm and 111 in TDF arm). Over 48 weeks of treatment, no significant differences were detected in declines in markers of inflammation and activation with MVC vs. TDF. A greater CD4 T-cell count increase (median +234 vs. +188 cells/μl, P = 0.036), a smaller CD8 T-cell count decrease (-6 vs. -109 cells/μl, P = 0.008), and a smaller CD4 : CD8 ratio increase (0.26 vs. 0.39, P = 0.003) occurred with MVC. Among participants with a baseline CD4 : CD8 ratio less than 1, a smaller proportion of MVC group normalized to a ratio greater than 1 at week 48 (15 and 36%, P < 0.001).

Conclusion: MVC resulted in less improvement in the CD4 : CD8 ratio driven by greater increase in CD4 cell count but smaller decline in CD8 cell count. Changes in soluble or cellular biomarkers of inflammation and immune activation were not different between MVC and TDF.
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http://dx.doi.org/10.1097/QAD.0000000000001181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966543PMC
August 2016

Cervical cancer survival in a resource-limited setting-North Central Nigeria.

Infect Agent Cancer 2016 24;11:15. Epub 2016 Mar 24.

Department of Obstetrics and Gynecology, University of Jos/Jos University Teaching Hospital, Jos, Plateau State Nigeria.

Background: Organized cervical cancer screening services are presently lacking in Nigeria contributing to late presentation and diagnosis of invasive cervical cancer cases (ICCs) at advanced stages in most gynecologic units in Nigeria. We evaluated outcomes of ICCs diagnosed at Jos University Teaching Hospital (JUTH) to better understand factors associated with cervical cancer survival in similar resource limited settings.

Methods: We performed a retrospective cohort study with a prospective follow up data to estimate time from diagnosis to mortality among women diagnosed with ICCs at JUTH. Women who were diagnosed with ICCs between January 2011 and May 2013 were followed up after initial evaluation at JUTH and subsequent referral for specialized treatment in one of the national oncology treatment centers in Nigeria. The main outcome measured was all-cause mortality rate and overall survival (OS) after diagnosis of ICC. The follow up data were updated and observations were censored March 31, 2015. The overall death rate was estimated using the total number of death events and the cumulative follow-up time from diagnosis to death. We conducted Cox proportional hazard regression to assess factors associated with death.

Results: A total of 65 histologically confirmed ICCs were followed up. The median age of the cohort was 50 years with a median parity of 7. The HIV prevalence in the cohort was 8.2 % and the majority (72.3 %) were diagnosed at advanced stages (AD) of ICC. Simple total abdominal hysterectomy (TAH) was performed in 38.9 % of patients who were diagnosed at early stage disease (ED). After a cumulative follow up of 526.17 months, 35 deaths occurred with an overall death rate of 79.8 per 100 women-years. We also found a significantly higher hazard of death in women with AD (HR = 3.3) and baseline anemia (HR = 3.0). In the subgroup of women with ED, the OS was significantly higher for those who had TAH compared to those who did not (26.5 versus 11.6 months respectively).

Conclusion: Advanced stage disease and baseline anemia were independently associated with higher death rate. Cervical cancer patients diagnosed at early stages by non-oncologic specialist in settings lacking the standard of care may benefit from improve survival with simple hysterectomy.
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http://dx.doi.org/10.1186/s13027-016-0062-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806480PMC
March 2016

Two-Drug Treatment Approaches in HIV: Finally Getting Somewhere?

Drugs 2016 Apr;76(5):523-31

Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, 645 N Michigan Ave, Suite 900, Chicago, IL, 60611, USA.

The advent of combination antiretroviral therapy (ART) has significantly decreased AIDS-related morbidity and mortality. Nevertheless, the benefits of ART are only realized through adherence to lifelong treatment. Though contemporary antiretroviral (ARV) drugs have fewer adverse effects in comparison to older ARV drugs, many agents are associated with negative or unknown long-term effects. There is increasing evidence that two-drug (dual-therapy) regimens may be an effective alternative to the currently recommended three-drug (triple-therapy) regimens. In this review, we provide a comprehensive and critical review of recently completed and ongoing trials of dual-therapy regimens in treatment-naïve and treatment-experienced HIV-1-infected patients. We also review current HIV/AIDS society recommendations regarding dual therapy as well as future therapeutic possibilities.
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http://dx.doi.org/10.1007/s40265-016-0553-8DOI Listing
April 2016

Artemether-Lumefantrine Exposure in HIV-Infected Nigerian Subjects on Nevirapine-Containing Antiretroviral Therapy.

Antimicrob Agents Chemother 2015 Dec 21;59(12):7852-6. Epub 2015 Sep 21.

Department of Pharmacy Practice, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Coadministration of nevirapine-based antiretroviral therapy (ART) and artemether-lumefantrine is reported to result in variable changes in lumefantrine exposure. We conducted an intensive pharmacokinetic study with 11 HIV-infected adults who were receiving artemether-lumefantrine plus nevirapine-based ART, and we compared the results with those for 16 HIV-negative adult historical controls. Exposure to artemether and lumefantrine was significantly lower and dihydroartemisinin exposure was unchanged in subjects receiving nevirapine-based ART, compared with controls. Nevirapine exposure was unchanged before and after artemether-lumefantrine administration.
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http://dx.doi.org/10.1128/AAC.01153-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649208PMC
December 2015

Contemporary issues on the epidemiology and antiretroviral adherence of HIV-infected adolescents in sub-Saharan Africa: a narrative review.

J Int AIDS Soc 2015 16;18:20049. Epub 2015 Sep 16.

Division of Infectious Diseases, Northwestern University, Chicago, IL, USA.

Introduction: Adolescents are a unique and sometimes neglected group in the planning of healthcare services. This is the case in many parts of sub-Saharan Africa, where more than eight out of ten of the world's HIV-infected adolescents live. Although the last decade has seen a reduction in AIDS-related mortality worldwide, largely due to improved access to effective antiretroviral therapy (ART), AIDS remains a significant contributor to adolescent mortality in sub-Saharan Africa. Although inadequate access to ART in parts of the subcontinent may be implicated, research among youth with HIV elsewhere in the world suggests that suboptimal adherence to ART may play a significant role. In this article, we summarize the epidemiology of HIV among sub-Saharan African adolescents and review their adherence to ART, emphasizing the unique challenges and factors associated with adherence behaviour.

Methods: We conducted a comprehensive search of online databases for articles, relevant abstracts, and conference reports from meetings held between 2010 and 2014. Our search terms included "adherence," "compliance," "antiretroviral use" and "antiretroviral adherence," in combination with "adolescents," "youth," "HIV," "Africa," "interventions" and the MeSH term "Africa South of the Sahara." Of 19,537 articles and abstracts identified, 215 met inclusion criteria, and 148 were reviewed.

Discussion: Adolescents comprise a substantial portion of the population in many sub-Saharan African countries. They are at particular risk of HIV and may experience worse outcomes. Although demonstrated to have unique challenges, there is a dearth of comprehensive health services for adolescents, especially for those with HIV in sub-Saharan Africa. ART adherence is poorer among older adolescents than other age groups, and psychosocial, socio-economic, individual, and treatment-related factors influence adherence behaviour among adolescents in this region. With the exception of a few examples based on affective, cognitive, and behavioural strategies, most adherence interventions have been targeted at adults with HIV.

Conclusions: Although higher levels of ART adherence have been reported in sub-Saharan Africa than in other well-resourced settings, adolescents in the region may have poorer adherence patterns. There is substantial need for interventions to improve adherence in this unique population.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575412PMC
http://dx.doi.org/10.7448/IAS.18.1.20049DOI Listing
April 2016

HIV Associated Chronic Obstructive Pulmonary Disease in Nigeria.

J AIDS Clin Res 2015 May;6(5)

Department of Medicine, Jos University Teaching Hospital, Jos, Nigeria.

Objective: To determine the prevalence and risk factors for chronic obstructive pulmonary disease (COPD) among HIV-infected adults in Nigeria.

Design: Cross-sectional study.

Methods: HIV-infected adults aged ≥ 30 years with no acute ailments accessing care at the antiretroviral therapy clinic of Jos University Teaching Hospital were enrolled consecutively. Participants were interviewed to obtain pertinent demographic and clinical information, including exposure to risk factors for COPD. Post-bronchodilator spirometry was carried out. HIV related information was retrieved from the clinic medical records. COPD case-definition was based on the Global Initiative for Obstructive Lung Disease (GOLD) criteria using post-bronchodilator FEV/FVC <0.7. COPD prevalence was also calculated using the lower limit of normal for FEV/FVC criteria (LLN) from the European Respiratory Society normative equation. Factors associated with COPD were determined using logistic regression models.

Results: Study population comprised 356 HIV infected adults with mean age of 44.5 (standard deviation, 7.1) years and 59% were female. The mean time elapsed since HIV diagnosis was 7.0 (SD, 2.6) years and 97.5% of the respondents were on stable ART with virologic suppression present in 67.2%. Prevalence of COPD were 15.4% (95% confidence interval [CI] 11.7-19.2), 12.07% (95% CI 8.67-15.48), 22.19% (95% CI 18.16-26.83) using GOLD, ERS LLN and GLI LLN diagnostic criteria respectively. In multivariate analyses adjusting for gender, exposure to cigarette smoke or biomass, history of pulmonary tuberculosis, use of antiretroviral therapy, current CD4 T-cell count and HIV RNA, only age > 50 years was independently associated with COPD with OR 3.4; 95% CI 1.42-8.17 when compared to ages 30-40 years.

Conclusion: HIV-associated COPD is common in our population of HIV patients.
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http://dx.doi.org/10.4172/2155-6113.1000453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521629PMC
May 2015

Less Bone Loss With Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study.

Clin Infect Dis 2015 Oct 9;61(7):1179-88. Epub 2015 Jun 9.

Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University, Baltimore, Maryland.

Background: There is a need to prevent or minimize bone loss associated with antiretroviral treatment (ART) initiation. We compared maraviroc (MVC)- to tenofovir disoproxil fumarate (TDF)-containing ART.

Methods: This was a double-blind, placebo-controlled trial. ART-naive subjects with human immunodeficiency virus type 1 RNA load (viral load [VL]) >1000 copies/mL and R5 tropism were randomized to MVC 150 mg or TDF 300 mg once daily (1:1), stratified by VL <100 000 or ≥100 000 copies/mL and age <30 or ≥30 years. All subjects received darunavir 800 mg, ritonavir 100 mg, and emtricitabine 200 mg daily. Dual-energy X-ray absorptiometry scanning was done at baseline and week 48. The primary endpoint was percentage change in total hip bone mineral density (BMD) from baseline to week 48 in the as-treated population.

Results: We enrolled 262 subjects. A total of 259 subjects (130 MVC, 129 TDF) contributed to the analyses (91% male; median age, 33 years; 45% white, 30% black, 22% Hispanic). Baseline median VL was 4.5 log10 copies/mL and CD4 count was 390 cells/µL. The decline in hip BMD (n = 115 for MVC, n = 109 for TDF) at week 48 was less with MVC (median [Q1, Q3] of -1.51% [-2.93%, -0.11%] vs -2.40% [-4.30%, -1.32%] for TDF (P < .001). Lumbar spine BMD decline was also less with MVC (median -0.88% vs -2.35%; P < .001). Similar proportions of subjects in both arms achieved VL ≤50 copies/mL in as-treated and ITT analyses.

Conclusions: MVC was associated with less bone loss at the hip and lumbar spine compared with TDF. MVC may be an option to attenuate ART-associated bone loss.

Clinical Trials Registration: NCT01400412.
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http://dx.doi.org/10.1093/cid/civ455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560904PMC
October 2015

Early suppressive antiretroviral therapy in HIV infection is associated with measurable changes in the corpus callosum.

J Neurovirol 2014 Oct 26;20(5):514-20. Epub 2014 Jun 26.

Department of Internal Medicine, Feinberg School of Medicine, Northwestern University, 251 East Huron Street, Galter Pavilion Suite 3-150, Chicago, IL, 60611, USA.

The purpose of this study was to examine the impact of early suppressive antiretroviral therapy (ART) on brain structure and neurocognitive outcomes. We conducted an observational study of subjects within 1 year of HIV infection. Ten ART-naïve and 10 ART-suppressed individuals were matched for age and infection duration and age-matched to 10 HIV-seronegative controls. Quantitative brain imaging and neurocognitive data were analyzed. Subjects on suppressive ART had diminished corpus callosum structural integrity on macromolecular and microstructural imaging, higher cerebrospinal fluid percent, higher depression scores, and lower functional performance. Early suppressive ART may alter the trajectory of neurological progression of HIV infection, particularly in the corpus callosum.
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http://dx.doi.org/10.1007/s13365-014-0261-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206660PMC
October 2014
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