Publications by authors named "Trevor A Crowell"

90 Publications

Temporal trends in self-reported HIV stigma and association with adherence and viral suppression in the African Cohort Study.

AIDS Care 2021 Oct 6:1-8. Epub 2021 Oct 6.

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

HIV stigma is a major barrier to HIV care and treatment among people living with HIV (PLWH). Evidence suggests that expansion in antiretroviral therapy (ART) may reduce stigma. However, there are limited longitudinal studies examining temporal trends in HIV stigma in sub-Saharan Africa in the Undetectable = Untransmittable (U = U) era. We longitudinally assessed temporal trends in self-reported experienced stigma and the association of experienced stigma with ART adherence and viral suppression among PLWH enrolled in the African Cohort Study (AFRICOS). AFRICOS is an ongoing cohort study enrolling PLWH in Uganda, Kenya, Tanzania, and Nigeria. As of 1 March 2020, 2937 PLWH enrolled in AFRICOS and had available data. In 2013, 22% of participants reported stigma at the enrollment visit and by 2018 the prevalence decreased to 1% overall and was below 2% for all countries. However, there was not a statistically significant change in stigma prevalence in our longitudinal models. In adjusted models, experiencing stigma was associated with a 0.67 decreased odds of ART Adherence (95% confidence interval (CI): 0.56-0.80) and a 0.64 decreased odds of viral suppression (95% CI: 0.73-0.99). HIV-associated stigma was associated with poor self-reported ART adherence and unsuppressed viral load.
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http://dx.doi.org/10.1080/09540121.2021.1984380DOI Listing
October 2021

Risk Factors for HIV sero-conversion in a high incidence cohort of men who have sex with men and transgender women in Bangkok, Thailand.

EClinicalMedicine 2021 Aug 17;38:101033. Epub 2021 Jul 17.

US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States.

Background: We measured Human Immunodeficiency (HIV) incidence, retention, and assessed risk factors for seroconversion among two previously unreported cohorts of men who have sex with men (MSM) and Transgender Women (TGW) in Bangkok, Thailand between 2017 and 2019.

Methods: We conducted an 18-month prospective cohort study of HIV-uninfected Thai cisgender men and TGW aged between 18 and 35 years who reported sex with men in the past six months and at least one additional risk factor for HIV infection. HIV and syphilis testing and computer-based behavioral questionnaires were administered at each visit. We utilized Poisson regression to calculate HIV incidence rates. A survival random forest model identified the most predictive risk factors for HIV sero-conversion and then used in a survival regression tree model to elucidate hazard ratios for individuals with groups of selected risk factors. Cox proportional hazards (pH) regression evaluated the strength of association between individual covariates and risk of sero-conversion.

Findings: From April 2017-October 2019, 1,184 participants were screened, 167 were found ineligible, and 1,017 enrolled. Over the 18-month study, visit retention was 93·4% (95% CI 91·6%-94·8%) and HIV incidence was 3·73 per 100 person-years (95% CI 2·79-5·87). Utilizing survival regression tree modeling, those who were 18-20 years of age, reported sexual attraction to mostly or only men, and had five or more lifetime sexual partners were 4·9 times more likely to seroconvert compared to other cohort participants. Factors associated with HIV incidence utilizing Cox pH regression included sexual attraction to mostly or only men (adjusted hazard ratio (aHR) 14·9 (95% CI 20·1-107·9), younger age (18-19 years, aHR 10·88 (95% CI 4·12-28·7), five or greater lifetime sexual partners (aHR 2·0, 95%CI 1·1-3·6), inconsistent condom use with casual partners (aHR 2·43, 95% CI 1·3-4·5), and prior HIV testing (adjusted HR 2·0, 95% CI 1·1-3·5).

Interpretation: Interpretation HIV incidence remains high among Bangkok-based MSM and TGW. These key populations expressed high interest in participating in efficacy evaluation of future prevention strategies and had high retention in this 18 month study.

Funding: Funding US National Institute of Allergy and Infectious Diseases (NIAID), Division of AIDS Interagency Agreements (DAIDS) and U.S. Department of the Army.
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http://dx.doi.org/10.1016/j.eclinm.2021.101033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413240PMC
August 2021

Epidemiological and clinical implications of asymptomatic malaria and schistosomiasis co-infections in a rural community in western Kenya.

BMC Infect Dis 2021 Sep 9;21(1):937. Epub 2021 Sep 9.

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Background: Malaria and schistosomiasis present considerable disease burden in tropical and sub-tropical areas and severity is worsened by co-infections in areas where both diseases are endemic. Although pathogenesis of these infections separately is well studied, there is limited information on the pathogenic disease mechanisms and clinical disease outcomes in co-infections. In this study, we investigated the prevalence of malaria and schistosomiasis co-infections, and the hematologic and blood chemistry abnormalities in asymptomatic adults in a rural fishing community in western Kenya.

Methods: This sub-study used samples and data collected at enrollment from a prospective observational cohort study (RV393) conducted in Kisumu County, Kenya. The presence of malaria parasites was determined using microscopy and real-time-PCR, and schistosomiasis infection by urine antigen analysis (CCA). Hematological analysis and blood chemistries were performed using standard methods. Statistical analyses were performed to compare demographic and infection data distribution, and hematologic and blood chemistry parameters based on different groups of infection categories. Clinically relevant hematologic conditions were analyzed using general linear and multivariable Poisson regression models.

Results: From February 2017 to May 2018, we enrolled 671 participants. The prevalence of asymptomatic Plasmodium falciparum was 28.2% (157/556) and schistosomiasis 41.2% (229/562), with 18.0% (100/556) of participants co-infected. When we analyzed hematological parameters using Wilcoxon rank sum test to evaluate median (IQR) distribution based on malarial parasites and/or schistosomiasis infection status, there were significant differences in platelet counts (p = 0.0002), percent neutrophils, monocytes, eosinophils, and basophils (p < 0.0001 each). Amongst clinically relevant hematological abnormalities, eosinophilia was the most prevalent at 20.6% (116/562), whereas thrombocytopenia was the least prevalent at 4.3% (24/562). In univariate model, Chi-Square test performed for independence between participant distribution in different malaria parasitemia/schistosomiasis infection categories within each clinical hematological condition revealed significant differences for thrombocytopenia and eosinophilia (p = 0.006 and p < 0.0001, respectively), which was confirmed in multivariable models. Analysis of the pairwise mean differences of liver enzyme (ALT) and kidney function (Creatinine Clearance) indicated the presence of significant differences in ALT across the infection groups (parasite + /CCA + vs all other groups p < .003), but no differences in mean Creatinine Clearance across the infection groups.

Conclusions: Our study demonstrates the high burden of asymptomatic malaria parasitemia and schistosomiasis infection in this rural population in Western Kenya. Asymptomatic infection with malaria or schistosomiasis was associated with laboratory abnormalities including neutropenia, leukopenia and thrombocytopenia. These abnormalities could be erroneously attributed to other diseases processes during evaluation of diseases processes. Therefore, evaluating for co-infections is key when assessing individuals with laboratory abnormalities. Additionally, asymptomatic infection needs to be considered in control and elimination programs given high prevalence documented here.
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http://dx.doi.org/10.1186/s12879-021-06626-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431856PMC
September 2021

SARS-CoV-2 antibody prevalence in people with and without HIV in rural western Kenya, January to March 2020.

AIDS 2021 Sep 1. Epub 2021 Sep 1.

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA HJF Medical Research International, Kericho, Kenya HJF Medical Research International, Kisumu, Kenya.

Abstract: Among 582 participants in Western Kenya who were retrospectively tested from January through March 2020, 19 (3.3%) had detectable SARS-CoV-2 antibodies. The prevalence of detectable SARS-CoV-2 antibodies was similar between participants with and without HIV (3.1% vs. 4.0%, p = 0.68). One participant reported a cough in the preceding week but others denied symptoms. These may represent cross-reactivity or asymptomatic infections that predated the first reported COVID-19 cases in Kenya.
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http://dx.doi.org/10.1097/QAD.0000000000003054DOI Listing
September 2021

Prevalence and predictors of food insecurity among people living with and without HIV in the African Cohort Study.

Public Health Nutr 2021 Aug 23:1-14. Epub 2021 Aug 23.

HJF Medical Research International, Abuja, Nigeria.

Objective: We determined the prevalence and identified predictors of food insecurity in four African countries.

Design: Cross-sectional analyses at study enrolment.

Setting: From January 2013 to March 2020, people living with HIV (PLWH) and without HIV were enrolled at twelve clinics in Kenya, Uganda, Tanzania and Nigeria.

Participants: Participants reporting not having enough food to eat over the past 12 months or receiving <3 meals/d were defined as food insecure. Robust Poisson regression models were used to estimate unadjusted and adjusted prevalence ratios (aPR) and 95 % CI for predictors of food insecurity among all participants and separately among PLWH.

Results: 1694/3496 participants (48·5 %) reported food insecurity at enrolment, with no difference by HIV status. Food insecurity was more common among older participants (50+ v. 18-24 years aPR 1·35, 95 % CI 1·15, 1·59). Having 2-5 (aPR 1·14, 95 % CI 1·01, 1·30) or >5 dependents (aPR 1·17, 95 % CI 1·02, 1·35), and residing in Kisumu West, Kenya (aPR 1·63, 95 % CI 1·42, 1·87) or Nigeria (aPR 1·20, 95 % CI 1·01, 1·41) was associated with food insecurity. Residing in Tanzania (aPR 0·65, 95 % CI 0·53, 0·80) and increasing education (secondary/above education v. none/some primary education aPR 0·73, 95 % CI 0·66, 0·81) was protective against food insecurity. Antiretroviral therapy (ART)-experienced PLWH were more likely to be food secure irrespective of viral load.

Conclusion: Food insecurity was highly prevalent in our cohort though not significantly associated with HIV. Policies aimed at promoting education, elderly care, ART access in PLWH and financial independence could potentially improve food security in Africa.
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http://dx.doi.org/10.1017/S136898002100361XDOI Listing
August 2021

Factors associated with testing for HIV and hepatitis C among behaviorally vulnerable men in Germany: a cross-sectional analysis upon enrollment into an observational cohort.

AIDS Res Ther 2021 08 16;18(1):52. Epub 2021 Aug 16.

Institute of Virology, Medical Faculty, University Bonn, Bonn, Germany.

Background: HIV and hepatitis C virus (HCV) have shared routes of transmission among men who have sex with men (MSM). Routine testing facilitates early diagnosis and treatment, thereby preventing morbidity and onward transmission. We evaluated factors associated with HIV and HCV testing in a behaviorally vulnerable cohort of predominantly MSM.

Methods: From June 2018 through June 2019, the BRAHMS study enrolled adults at ten German outpatient clinics that serve gender and sexual minority populations. Participants completed behavioral questionnaires that captured prior experience with HIV and HCV testing. Multivariable robust Poisson regression was used to evaluate factors potentially associated with testing in the previous 6 months.

Results: Among 1017 participants with median age 33 (interquartile range 28-39) years, 1001 (98.4%) reported any lifetime history of HIV testing and 787 (77.4%) reported any HCV testing, including 16 (1.6%) known to be living with HCV. Testing within the last 6 months was reported by 921 (90.6%) and 513 (50.4%) for HIV and HCV, respectively. Recent HIV testing was more common among participants with higher education level and recent HCV testing. Recent HCV testing was more common among participants with non-cisgender identity, lifetime history of illicit drug use, hepatitis B immunity or infection, and recent HIV testing.

Conclusion: Prior testing for HIV was common in this cohort, but interventions are needed to improve HCV risk stratification and access to testing. HIV testing infrastructure can be successfully leveraged to support HCV testing, but differentiated preventive care delivery is needed for some vulnerable populations.
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http://dx.doi.org/10.1186/s12981-021-00378-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365908PMC
August 2021

Persons living with HIV in sero-discordant partnerships experience improved HIV care engagement compared with persons living with HIV in sero-concordant partnerships: a cross-sectional analysis of four African countries.

AIDS Res Ther 2021 07 22;18(1):43. Epub 2021 Jul 22.

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, New York, MD, USA.

Background: Persons living with HIV (PLWH) who are members of sero-discordant and sero-concordant relationships may experience psychological stressors or motivators that affect HIV care. We assessed the association between sero-discordance status, antiretroviral therapy (ART) uptake, and viral suppression in the African Cohort Study (AFRICOS).

Methods: AFRICOS enrolls PLWH and HIV-uninfected individuals at 12 sites in Uganda, Kenya, Tanzania, and Nigeria. At enrollment, we determined ART use through self-report. Viral suppression was defined as HIV RNA < 1000 copies/mL. We analyzed PLWH who were index participants within two types of sexual dyads: sero-discordant or sero-concordant. Binomial regression models were used to estimate prevalence ratios (PRs) and 95% confidence intervals (95% CIs) for factors associated with ART use and viral suppression at study enrollment.

Results: From January 2013 through March 2018, 223 index participants from sero-discordant dyads and 61 from sero-concordant dyads were enrolled. The majority of the indexes were aged 25-34 years (50.2%), female (53.4%), and married (96.5%). Sero-discordant indexes were more likely to disclose their status to partners compared with sero-concordant indexes (96.4% vs. 82.0%, p < 0.001). After adjustment, sero-discordant index participants were more likely to be on ART (aPR 2.8 [95% CI 1.1-6.8]), but no more likely to be virally suppressed. Results may be driven by unique psycho-social factors and global implementation of treatment as prevention.

Conclusions: PLWH in sero-discordant sexual partnerships demonstrated improved uptake of ART compared with those in sero-concordant partnerships. Interventions are needed to increase care engagement by individuals in sero-concordant relationships to improve HIV outcomes.
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http://dx.doi.org/10.1186/s12981-021-00363-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296539PMC
July 2021

Assessing the impact of HIV support groups on antiretroviral therapy adherence and viral suppression in the African cohort study.

BMC Infect Dis 2021 Jul 20;21(1):694. Epub 2021 Jul 20.

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Background: Support groups for people living with HIV (PLWH) may improve HIV care adherence and outcomes. We assessed the impact of support group attendance on antiretroviral therapy (ART) adherence and viral suppression in four African countries.

Methods: The ongoing African Cohort Study (AFRICOS) enrolls participants at 12 clinics in Kenya, Uganda, Tanzania, and Nigeria. Self-reported attendance of any support group meetings, self-reported ART adherence, and HIV RNA are assessed every 6 months. Logistic regression models with generalized estimating equations were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) for support group attendance and other factors potentially associated with ART adherence and viral suppression.

Results: From January 2013 to December 1, 2019, 1959 ART-experienced PLWH were enrolled and 320 (16.3%) reported any support group attendance prior to enrollment. Complete ART adherence, with no missed doses in the last 30 days, was reported by 87.8% while 92.4% had viral suppression <1000copies/mL across all available visits. There was no association between support group attendance and ART adherence in unadjusted (OR 1.01, 95% CI 0.99-1.03) or adjusted analyses (aOR 1.00, 95% CI 0.98-1.02). Compared to PLWH who did not report support group attendance, those who did had similar odds of viral suppression in unadjusted (OR 0.99, 95% CI 0.978-1.01) and adjusted analyses (aOR 0.99, 95% CI 0.97-1.01).

Conclusion: Support group attendance was not associated with significantly improved ART adherence or viral suppression, although low support group uptake may have limited our ability to detect a statistically significant impact.
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http://dx.doi.org/10.1186/s12879-021-06390-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290579PMC
July 2021

Brief Report: Increased Inflammation and Liver Disease in HIV/HBV-Coinfected Individuals.

J Acquir Immune Defic Syndr 2021 Nov;88(3):310-313

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD.

Objective: HIV and hepatitis B virus (HBV) coinfection can accelerate morbidity and mortality, especially in sub-Saharan Africa where both infections are common. Although inflammation contributes to disease progression, more information is needed to better understand the pathology. This study compared markers of cirrhosis and inflammation in HIV/HBV-coinfected individuals compared with monoinfected and uninfected patients.

Setting: The HIV/HBV-coinfected subjects from the Ugandan arm of the prospective African Cohort Study were selected for evaluation and matched by age and gender with HIV-monoinfected, HBV-monoinfected, and uninfected controls.

Methods: Plasma samples were used to quantify markers of immune activation and inflammation. The FIB-4 (a simple index to predict significant liver fibrosis) score was used to estimate liver fibrosis. Demographic and laboratory characteristics were compared across the groups.

Results: Together, 31 HIV/HBV-coinfected participants were identified and compared with 62 HIV-monoinfected, 7 HBV-monoinfected, and 62 uninfected controls. The HIV/HBV-coinfected group had generally higher levels of inflammation. Most notably, matrix metalloproteinase-2, matrix metalloproteinase-9, and fibroblast growth factor-19 levels were dysregulated among the HIV/HBV-coinfected individuals. Furthermore, the FIB-4 score was higher in the HIV/HBV-coinfected group compared with the HIV-monoinfected group and revealed that 11% of HIV/HBV-coinfected individuals had evidence of undiagnosed advanced liver disease.

Conclusions: Differences in levels of inflammation exist between individuals with HIV/HBV coinfection compared with monoinfected and uninfected controls. A distinct signature of inflammation was associated with HIV/HBV coinfection that could reflect the mechanism of liver fibrosis and increased risk for disease progression. Finally, there may be an underappreciated amount of undiagnosed advanced liver disease in sub-Saharan Africa.
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http://dx.doi.org/10.1097/QAI.0000000000002760DOI Listing
November 2021

Hepatitis B virus infection among men who have sex with men and transgender women living with or at risk for HIV: a cross sectional study in Abuja and Lagos, Nigeria.

BMC Infect Dis 2021 Jul 6;21(1):654. Epub 2021 Jul 6.

Department of Epidemiology and Public Health, University of Maryland, School of Medicine, Baltimore, MD, USA.

Background: Despite the development of a safe and efficacious hepatitis B vaccine in 1982, the hepatitis B virus (HBV) remains a public health burden in sub-Saharan Africa. Due to shared risk factors for virus acquisition, men who have sex with men (MSM) and transgender women (TGW) living with HIV are at increased risk of HBV. We estimated the prevalence of HBV and associated factors for MSM and TGW living with or without HIV in Nigeria.

Methods: Since March 2013, TRUST/RV368 has recruited MSM and TGW in Abuja and Lagos, Nigeria using respondent driven sampling. Participants with HIV diagnosis, enrollment as of June 2015, and available plasma were selected for a cross-sectional study and retrospectively tested for hepatitis B surface antigen and HBV DNA. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with prevalent HBV infection.

Results: A total of 717 MSM and TGW had a median age of 25 years (interquartile range [IQR]: 21-27), 5% self-reported HBV vaccination, 61% were living with HIV, 10% had prevalent HBV infection and 6% were HIV-HBV co-infected. HIV mono-infected as compared to HIV-HBV co-infected had a higher median CD4 T cell count [425 (IQR: 284-541) vs. 345 (IQR: 164-363) cells/mm, p = 0.03] and a lower median HIV RNA viral load [4.2 (IQR: 2.3-4.9) vs. 4.7 (IQR: 3.9-5.4) logcopies/mL, p < 0.01]. The only factor independently associated with HBV was self-report of condomless sex at last anal intercourse (OR: 2.2, 95% CI: 1.3, 3.6). HIV infection was not independently associated with HBV (OR: 1.0, 95% CI: 0.7-1.6).

Conclusion: HBV prevalence was moderately high but did not differ by HIV in this cohort of MSM and TGW. Recent condomless sex was associated with elevated HBV risk, reinforcing the need to increase communication and education on condom use among key populations in Nigeria. Evaluating use of concurrent HIV antiretroviral therapy with anti-HBV activity may confirm the attenuated HBV prevalence for those living with HIV.
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http://dx.doi.org/10.1186/s12879-021-06368-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259010PMC
July 2021

Brief Report: Prevalence Trend of Transmitted Drug Resistance in a Prospective Cohort of Thai People With Acute HIV Infection.

J Acquir Immune Defic Syndr 2021 Aug;87(5):1173-1177

SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Background: The greater availability of different antiretroviral therapy regimens in developing countries may influence the emergence of transmitted drug resistance (TDR). People with acute HIV infection (AHI) represent the best opportunity for real-time monitoring of TDR. This study assessed the TDR prevalence trends over time in a Thai cohort of predominantly men who have sex with men (MSM) with AHI.

Methods: At the time of RV254/SEARCH010 study (NCT00796146) enrollment and before starting ART, HIV genotyping was used to identify mutations in the reverse transcriptase and protease genes. Testing for TDR mutations was obtained by a validated in-house method with TRUGENE assay in a subset. Genotype sequences were analyzed using the Stanford University HIV Drug Resistance Database.

Results: Genotyping was performed for 573 participants with AHI. Their median age was 26 years (interquartile range 22-31), 97.4% were men, and 94.1% were MSM. Overall TDR prevalence was 7.0%, declining from 12.5% in 2009-2010 to 4.8% in 2017-2018. A declining resistance prevalence to nonnucleoside reverse transcriptase inhibitor emerged from 9.4% in 2009-2010 to 3.5% in 2017-2018 and to nucleoside reverse transcriptase inhibitor from 6.3% to 2.1%. Protease inhibitor resistance showed a decreased TDR level from 3.1% in 2009-2010 to 1.4% in 2017-2018.

Conclusions: We report an encouraging declining trend in TDR prevalence in a Thai cohort of mainly MSM from 2009 to 2018; in 2017-2018, we observed a low TDR prevalence according to the World Health Organization definition.
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http://dx.doi.org/10.1097/QAI.0000000000002718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260960PMC
August 2021

Brief Report: Prevalence Trend of Transmitted Drug Resistance in a Prospective Cohort of Thai People With Acute HIV Infection.

J Acquir Immune Defic Syndr 2021 Aug;87(5):1173-1177

SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Background: The greater availability of different antiretroviral therapy regimens in developing countries may influence the emergence of transmitted drug resistance (TDR). People with acute HIV infection (AHI) represent the best opportunity for real-time monitoring of TDR. This study assessed the TDR prevalence trends over time in a Thai cohort of predominantly men who have sex with men (MSM) with AHI.

Methods: At the time of RV254/SEARCH010 study (NCT00796146) enrollment and before starting ART, HIV genotyping was used to identify mutations in the reverse transcriptase and protease genes. Testing for TDR mutations was obtained by a validated in-house method with TRUGENE assay in a subset. Genotype sequences were analyzed using the Stanford University HIV Drug Resistance Database.

Results: Genotyping was performed for 573 participants with AHI. Their median age was 26 years (interquartile range 22-31), 97.4% were men, and 94.1% were MSM. Overall TDR prevalence was 7.0%, declining from 12.5% in 2009-2010 to 4.8% in 2017-2018. A declining resistance prevalence to nonnucleoside reverse transcriptase inhibitor emerged from 9.4% in 2009-2010 to 3.5% in 2017-2018 and to nucleoside reverse transcriptase inhibitor from 6.3% to 2.1%. Protease inhibitor resistance showed a decreased TDR level from 3.1% in 2009-2010 to 1.4% in 2017-2018.

Conclusions: We report an encouraging declining trend in TDR prevalence in a Thai cohort of mainly MSM from 2009 to 2018; in 2017-2018, we observed a low TDR prevalence according to the World Health Organization definition.
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http://dx.doi.org/10.1097/QAI.0000000000002718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260960PMC
August 2021

Persons living with HIV treated in acute HIV infection report good health-related quality of life in Thailand.

AIDS Care 2021 Jun 30:1-8. Epub 2021 Jun 30.

SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

The health-related quality of life (HRQoL) among persons living with HIV (PLWHA) who initiate ART during acute HIV infection (AHI) is not well studied. Participants in the SEARCH010/RV254 cohort initiated ART during AHI. They completed the Thai version of the World Health Organisation Quality of Life instrument-BREF (WHOQOL-BREF) and Patient Health Questionnaire-9 (PHQ-9) prior to ART initiation and 24 weeks later. Of 452 participants, 406 (90%) completed the WHOQOL-BREF. The median age was 26 years (IQR 22-31), and 98% were men. All WHOQOL-BREF domains demonstrated good internal consistency (Cronbach's alpha >0.70). Confirmatory factor analysis validated the WHOQOL-BREF model. 90% of Pearson correlations between domain scores and general facet items were >0.50. HRQoL in all domains was worse among those with at least moderately severe depression (PHQ-9 ≥ 10) (<0.0001), supporting discriminant validity. At 24 weeks, there was an improvement of scores in all domains (physical, psychological, social, and environmental) and general facet items (<0.0001), and the range of mean domain scores was 14.7-15.6 (SD 2.3-2.8). The majority of participants (58-63%) had improved HRQoL in the physical, psychological and environmental domains. It is concluded that HRQoL improves 6 months after initiation of ART in AHI, suggesting a benefit of early ART initiation.
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http://dx.doi.org/10.1080/09540121.2021.1944596DOI Listing
June 2021

Hepatitis and tuberculosis testing are much less common than HIV testing among adults in Kisumu, Kenya: results from a cross-sectional assessment.

BMC Public Health 2021 06 15;21(1):1143. Epub 2021 Jun 15.

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Background: Kenya has a high burden of HIV, viral hepatitis, and tuberculosis. Screening is necessary for early diagnosis and treatment, which reduces morbidity and mortality across all three illnesses. We evaluated testing uptake for HIV, viral hepatitis, and tuberculosis in Kisumu, Kenya.

Methods: Cross-sectional data from adults aged 18-35 years who enrolled in a prospective HIV incidence cohort study from February 2017 to May 2018 were analyzed. A questionnaire was administered to each participant at screening for study eligibility to collect behavioral characteristics and to assess prior testing practices. Among participants without a history of previously-diagnosed HIV, multivariable robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for factors potentially associated with HIV testing in the 12 months prior to enrollment. A hierarchical model was used to test for differential access to testing due to spatial location.

Results: Of 671 participants, 52 (7.7%) were living with HIV, 308 (45.9%) were female, and the median age was 24 (interquartile range 21-28) years. Among 651 (97.0%) who had ever been tested for HIV, 400 (61.2%) reported HIV testing in the past 6 months, 129 (19.7%) in the past 6-12 months, and 125 (19.1%) more than one year prior to enrollment. Any prior testing for viral hepatitis was reported by 8 (1.2%) participants and for tuberculosis by 51 (7.6%). In unadjusted models, HIV testing in the past year was more common among females (PR 1.08 [95% CI 1.01, 1.17]) and participants with secondary education or higher (PR 1.10 [95% CI 1.02, 1.19]). In the multivariable model, only secondary education or higher was associated with recent HIV testing (adjusted PR 1.10 [95% CI 1.02, 1.20]). Hierarchical models showed no geographic differences in HIV testing across Kisumu subcounties.

Conclusions: Prior HIV testing was common among study participants and most had been tested within the past year but testing for tuberculosis and viral hepatitis was far less common. HIV testing gaps exist for males and those with lower levels of education. HIV testing infrastructure could be leveraged to increase access to testing for other endemic infectious diseases.
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http://dx.doi.org/10.1186/s12889-021-11164-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204299PMC
June 2021

Transient reductions in HIV clinic attendance and food security during the COVID-19 pandemic for people living with HIV in four African countries.

Clin Infect Dis 2021 Apr 27. Epub 2021 Apr 27.

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD.

The COVID-19 pandemic and associated public health responses have disrupted daily living activities with economic and health consequences globally. We observed transient decreases in HIV clinic visit adherence and food security among PLWH early in the pandemic, and an increase in viral suppression later in the pandemic.
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http://dx.doi.org/10.1093/cid/ciab379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135576PMC
April 2021

Factors associated with sexually transmitted infections among care-seeking adults in the African Cohort Study.

BMC Public Health 2021 04 16;21(1):738. Epub 2021 Apr 16.

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Objectives: Sexually transmitted infections (STIs) are a major cause of morbidity. Understanding drivers of transmission can inform effective prevention programs. We describe STI prevalence and identify factors associated with STIs in four African countries.

Methods: The African Cohort Study is an ongoing, prospective cohort in Kenya, Nigeria, Tanzania and Uganda. At enrollment, a physical exam was conducted and STI diagnosis made by a clinician using a syndromic management approach. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) for factors associated with an STI diagnosis.

Results: As of June 2020, 3544 participants were enrolled. STI prevalence was 7.7% and did not differ by HIV status (p = 0.30). Prevalence differed by syndrome (3.5% vaginal discharge, 1.5% genital ulcer, 2.1% lower abdominal pain, 0.2% inguinal bubo). The odds of having an STI were higher at all sites compared to Kisumu West, Kenya, and among those with a primary level education or below compared to those with secondary or higher (aOR: 1.77; 95% CI: 1.32-2.38). The odds of an STI diagnosis was higher among participants 18-29 years (aOR: 2.29; 95% CI: 1.35-3.87), females (aOR: 2.64; 95% CI: 1.94-3.59), and those with depression (aOR: 1.78; 95% CI: 1.32-2.38). Among PLWH, similar factors were independently associated with an STI diagnosis. Viral suppression was protective against STIs (aOR: 2.05; 95% CI: 1.32-3.20).

Conclusions: Prevalence of STIs varied by site with young people and females most at risk for STIs. Mental health is a potential target area for intervention.
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http://dx.doi.org/10.1186/s12889-021-10762-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052711PMC
April 2021

Clinical laboratory reference values in adults in Kisumu County, Western Kenya; hematology, chemistry and CD4.

PLoS One 2021 30;16(3):e0249259. Epub 2021 Mar 30.

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.

Background: Clinical laboratory reference intervals (RIs) are essential for diagnosing and managing patients in routine clinical care as well as establishing eligibility criteria and defining adverse events in clinical trials, but may vary by age, gender, genetics, nutrition and geographic location. It is, therefore, critical to establish region-specific reference values in order to inform clinical decision-making.

Methods: We analyzed data from a prospective observational HIV incidence cohort study in Kombewa, Kenya. Study participants were healthy males and females, aged 18-35 years, without HIV. Median and 95% reference values (2.5th percentile to 97.5th percentile) were calculated for laboratory parameters including hematology, chemistry studies, and CD4 T cell count. Standard Deviation Ratios (SDR) and Bias Ratios (BR) are presented as measures of effect magnitude. Findings were compared with those from the United States and other Kenyan studies.

Results: A total of 299 participants were analyzed with a median age of 24 years (interquartile range: 21-28). Ratio of males to females was 0.9:1. Hemoglobin range (2.5th-97.5th percentiles) was 12.0-17.9 g/dL and 9.5-15.3 g/dL in men and women respectively. In the cohort, MCV range was 59-95fL, WBC 3.7-9.2×103/μL, and platelet 154-401×103/μL. Chemistry values were higher in males; the creatinine RI was 59-103 μmol/L in males vs. 46-76 μmol/L in females (BRUL>.3); and the alanine transferase range was 8.8-45.3 U/L in males vs. 7.5-36.8 U/L in females (SDR>.3). The overall CD4 T cell count RI was 491-1381 cells/μL. Some parameters including hemoglobin, neutrophil, creatinine and ALT varied with that from prior studies in Kenya and the US.

Conclusion: This study not only provides clinical reference intervals for a population in Kisumu County but also highlights the variations in comparable settings, accentuating the requirement for region-specific reference values to improve patient care, scientific validity, and quality of clinical trials in Africa.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249259PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009432PMC
October 2021

The pregnancy factor: the prevalence of depression among women living with HIV enrolled in the African Cohort Study (AFRICOS) by pregnancy status.

Arch Womens Ment Health 2021 08 8;24(4):649-658. Epub 2021 Mar 8.

Department of Pediatrics, Uniformed Services University, 4301 Jones Bridge Rd, Bethesda, MD, 20814, USA.

Among Sub-Saharan African women living with HIV (WLWH), pregnancy creates unique stressors that may cause depression. We describe the prevalence of depression among WLWH enrolled in the African Cohort Study (AFRICOS) by pregnancy status and describe factors associated with depression. WLWH < 45 years of age underwent six-monthly visits with depression diagnosed using the Center for Epidemiological Studies-Depression scale. Visits were categorized as "pregnant;" "postpartum" (the first visit made after the last pregnancy visit), and "non-pregnant." The prevalence of depression was calculated for each visit type and compared using prevalence odds ratios (POR) with 95% confidence intervals (CI). Logistic regression with generalized estimating equations was used to evaluate sociodemographic factors associated with depression. From January 2013 to March 1, 2020, 1333 WLWH were enrolled, and 214 had pregnancies during follow-up. As compared to the prevalence of depression during "non-pregnant" visits (9.1%), depression was less common at "pregnant" (6.3%; POR = 0.68 [CI: 0.42, 1.09]) and "postpartum" (3.4%; POR = 0.36 [CI: 0.17, 0.76]) visits. When controlling for other factors, the visit category was not independently associated with depression. Visit number, study site, employment status, and food security were independently associated with decreased odds of depression. We observed a lower prevalence of depression during pregnancy and the postpartum period than has been previously described among WLWH during similar time points. We observed protective factors against depression which highlight the impact that holistic and consistent health care at HIV-centered clinics may have on the well-being of WLWH in AFRICOS.
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http://dx.doi.org/10.1007/s00737-021-01117-4DOI Listing
August 2021

COVID-19 preparedness: capacity to manufacture vaccines, therapeutics and diagnostics in sub-Saharan Africa.

Global Health 2021 03 3;17(1):24. Epub 2021 Mar 3.

, COVID-19 Think Tank, Nigeria.

Objective: The COVID-19 pandemic is a biosecurity threat, and many resource-rich countries are stockpiling and/or making plans to secure supplies of vaccine, therapeutics, and diagnostics for their citizens. We review the products that are being investigated for the prevention, diagnosis, and treatment of COVID-19; discuss the challenges that countries in sub-Saharan Africa may face with access to COVID-19 vaccine, therapeutics, and diagnostics due to the limited capacity to manufacture them in Africa; and make recommendations on actions to mitigate these challenges and ensure health security in sub-Saharan Africa during this unprecedented pandemic and future public-health crises.

Main Body: Sub-Saharan Africa will not be self-reliant for COVID-19 vaccines when they are developed. It can, however, take advantage of existing initiatives aimed at supporting COVID-19 vaccine access to resource-limited settings such as partnership with AstraZeneca, the Coalition for Epidemic Preparedness and Innovation, the Global Alliance for Vaccine and Immunisation, the Serum Institute of India, and the World Health Organization's COVID-19 Technology Access Pool. Accessing effective COVID-19 therapeutics will also be a major challenge for countries in sub-Saharan Africa, as production of therapeutics is frequently geared towards profitable Western markets and is ill-adapted to sub-Saharan Africa realities. The region can benefit from pooled procurement of COVID-19 therapy by the Africa Centres for Disease Control and Prevention in partnership with the African Union. If the use of convalescent plasma for the treatment of patients who are severely ill is found to be effective, access to the product will be minimally challenging since the region has a pool of recovered patients and human resources that can man supportive laboratories. The region also needs to drive the local development of rapid-test kits and other diagnostics for COVID-19.

Conclusion: Access to vaccines, therapeutics, and diagnostics for COVID-19 will be a challenge for sub-Saharan Africans. This challenge should be confronted by collaborating with vaccine developers; pooled procurement of COVID-19 therapeutics; and local development of testing and diagnostic materials. The COVID-19 pandemic should be a wake-up call for sub-Saharan Africa to build vaccines, therapeutics, and diagnostics manufacturing capacity as one of the resources needed to address public-health crises.
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http://dx.doi.org/10.1186/s12992-021-00668-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927760PMC
March 2021

False reactive HIV-1 diagnostic test results in an individual from Kenya on multiple testing platforms-A case report.

IDCases 2021 25;23:e01035. Epub 2020 Dec 25.

HJF Medical Research International, Kisumu, Kenya.

Background: Rapid diagnostic tests (RDT) are routinely used in screening for HIV infection. More complex diagnostic algorithms incorporating fourth-generation screening and confirmatory HIV-1/HIV-2 differentiation immunoassays (IA) may be used to confirm HIV infection. Co-infections and autoimmune diseases may lead to falsely reactive HIV diagnostic test results.

Case Presentation: A Kenyan man with asymptomatic schistosomiasis and low risk factors for HIV infection demonstrated an inconsistent and discordant pattern of reactivity on HIV RDT, repeated reactivity on fourth-generation IA and positive at a single time-point for HIV-1 on the Geenius HIV1/HIV2 confirmatory assay during the course of a prospective cohort study with HIV repeat testing. The individual initiated antiretroviral therapy following HIV diagnosis. However, his bi-annual behavioral questionnaire suggested low-risk factors for infection. Supplementary confirmatory serologic and nucleic acid tests were performed and gave discordant results. The participant was determined to be HIV uninfected using cell-associated HIV-1 DNA/RNA testing and antiretroviral therapy was discontinued.

Discussion And Conclusions: Sole reliance on diagnostic test results may result in misdiagnosis of HIV infection, social harm and potential antiretroviral induced drug toxicity. Interpretation of HIV test results should incorporate multiple parameters.
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http://dx.doi.org/10.1016/j.idcr.2020.e01035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808907PMC
December 2020

Field evaluation of HIV-1 viral load monitoring in adults and children receiving antiretroviral treatment in Nigeria by dried blood spot testing with RealTime HIV-1 on m2000.

J Clin Virol 2021 02 25;135:104694. Epub 2020 Nov 25.

Institute of Human Virology Nigeria, Abuja, Federal Capital Territory, Nigeria; Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA; Africa Centers for Disease Control and Prevention (Africa CDC), African Union Commission, Addis Ababa, Ethiopia; Kanazawa University, Graduate Medical Sciences, Kanazawa, Japan. Electronic address:

In resource-limited settings, use of dried blood spots (DBS) could be a pragmatic alternative to plasma for VL monitoring in people living with HIV (PLWH). We compared results from DBS to standard plasma VL testing under field conditions in patients receiving antiretroviral therapy (ART). DBS cards were prepared from venous blood (V-DBS), finger-pricks using micro-capillary tubes (M-DBS), and direct spotting (D-DBS). DBS and matched EDTA plasma were tested on the Abbott m2000 platform using the appropriate RealTime HIV-1 quantitative CE protocol. Matched plasma samples were also tested on the Roche COBAS Ampliprep/COBAS TaqMan version 2.0. Diagnostic accuracy indicators (sensitivity, specificity, misclassification rate, and kappa coefficient) for viral failure (VF) based on different VL threshold levels and agreement of absolute VL were calculated. A total of 669 participants provided 2676 samples. V-DBS had a peak sensitivity for VF of 89.1 % [95 % CI: 85.5-92.7] at the 1000 copies/mL threshold and a peak specificity of 97.4 % [95 % CI: 95.9-99.0] at the 5000 copies/mL threshold. The lowest proportion of upward misclassification (patients classified with VF who actually had viral suppression) for V-DBS was 3.1 % [95 % CI: 1.4-4.8] at the 5000 copies/mL threshold, whereas the lowest proportion of downward misclassification (patients classified as undetectable who actually had VF) was 10.9 % [95 % CI: 7.2-14.5] at the 1000 copies/mL threshold. Abbott RealTime HIV-1 VL results from all 3 DBS types for adults and children showed strong correlation with the gold standard plasma-based assay. DBS could be useful for monitoring VL in resource limited settings such as Nigeria.
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http://dx.doi.org/10.1016/j.jcv.2020.104694DOI Listing
February 2021

Brief Report: Syphilis Incidence and Effect on Viral Load, CD4, and CD4/CD8 Ratio in a Thai Cohort of Predominantly Men Who Have Sex With Men Living With HIV.

J Acquir Immune Defic Syndr 2021 02;86(2):219-223

SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Background: Syphilis has been increasing in the past years, especially among men who have sex with men (MSM). The aim of the study was to assess syphilis prevalence and incidence and changes in CD4 count and viremia in the RV254 cohort of persons living with HIV who initiated antiretroviral therapy during acute HIV infection (AHI) in Bangkok, Thailand.

Methods: From 2009 to 2018, all cohort participants with AHI were tested for syphilis using a qualitative treponemal chemiluminescent microparticle immunoassay and rapid plasma reagin on enrollment, every 24-48 weeks thereafter and when clinically indicated. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with incident syphilis.

Results: Among 579 participants, the median age was 26 (interquartile range: 22-31) years and 564 (97.4%) were men. Syphilis prevalence at enrollment was 14.3% and incidence was 10.2 cases per 100 person-years. Participants with syphilis were more likely to be MSM (HR 3.68, 95% CI: 1.16 to 11.62), use methamphetamine (HR 2.31, 95% CI: 1.51 to 3.54), and have hepatitis C (HR 2.63, 95% CI: 1.59 to 4.34). HIV RNA >50 copies/mL occurred in 6 (3.9%) participants at incident syphilis diagnosis and in 6 (3.9%) after syphilis treatment. Median CD4 count (cells/mm3) declined from 663 before syphilis to 624 at syphilis diagnosis (P = 0.07), rising again to 660 after syphilis treatment.

Conclusion: Syphilis was common in the RV254 cohort, inducing a marginal but significant impact on HIV RNA and a temporary decline in CD4. Syphilis screening and behavioral risk reduction counseling should be implemented for MSM with AHI in Thailand.
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http://dx.doi.org/10.1097/QAI.0000000000002542DOI Listing
February 2021

Novel Criteria for Diagnosing Acute and Early Human Immunodeficiency Virus Infection in a Multinational Study of Early Antiretroviral Therapy Initiation.

Clin Infect Dis 2021 08;73(3):e643-e651

Lundquist Institute at Harbor-University of California-Los Angeles Medical Center, Torrance, California, USA.

Background: Antiretroviral therapy (ART) initiation during acute and early human immunodeficiency virus infection (AEHI) limits HIV reservoir formation and may facilitate post-ART control but is logistically challenging. We evaluated the performance of AEHI diagnostic criteria from a prospective study of early ART initiation.

Methods: AIDS Clinical Trials Group A 5354 enrolled adults at 30 sites in the Americas, Africa, and Asia who met any 1 of 6 criteria based on combinations of results of HIV RNA, HIV antibody, Western blot or Geenius assay, and/or the signal-to-cutoff (S/CO) ratio of the ARCHITECT HIV Ag/Ab Combo or GS HIV Combo Ag/Ab EIA. HIV status and Fiebig stage were confirmed by centralized testing.

Results: From 2017 through 2019, 195 participants were enrolled with median age of 27 years (interquartile range, 23-39). Thirty (15.4%) were female. ART was started by 171 (87.7%) on the day of enrollment and 24 (12.3%) the next day. AEHI was confirmed in 188 (96.4%) participants after centralized testing, 4 (2.0%) participants were found to have chronic infection, and 3 (1.5%) found not to have HIV discontinued ART and were withdrawn. Retrospectively, a nonreactive or indeterminate HIV antibody on the Geenius assay combined with ARCHITECT S/CO ≥10 correctly identified 99 of 122 (81.2%) Fiebig II-IV AEHI cases with no false-positive results.

Conclusions: Novel AEHI criteria that incorporate ARCHITECT S/CO facilitated rapid and efficient ART initiation without waiting for an HIV RNA result. These criteria may facilitate AEHI diagnosis, staging, and immediate ART initiation in future research studies and clinical practice.

Clinical Trials Registration: NCT02859558.
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http://dx.doi.org/10.1093/cid/ciaa1893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326583PMC
August 2021

Ophthalmic Disease Prevalence and Incidence among People Living with Human Immunodeficiency Virus in the AFRICOS Study.

Ophthalmology 2021 07 11;128(7):1104-1107. Epub 2020 Dec 11.

Department of Ophthalmology, Walter Reed National Military Medical Center, Bethesda, Maryland; Department of Surgery, Uniformed Services University of Health Science, Bethesda, Maryland. Electronic address:

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http://dx.doi.org/10.1016/j.ophtha.2020.12.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192584PMC
July 2021

Attaining 95-95-95 through Implementation Science: 15 Years of Insights and Best Practices from the Walter Reed Army Institute of Research's Implementation of the U.S. President's Emergency Plan for AIDS Relief.

Am J Trop Med Hyg 2021 01;104(1):12-25

2The Uniformed Services University of the Health Sciences, Bethesda, Maryland.

The Walter Reed Army Institute of Research (WRAIR) supports more than 350,000 people on lifesaving HIV treatment in Kenya, Nigeria, Tanzania, and Uganda through funding from the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). Here, we review and synthesize the range of impacts WRAIR's implementation science portfolio has had on PEPFAR service delivery for military and civilian populations since 2003. We also explore how investments in implementation science create institutional synergies within the U.S. Department of Defense, contributing to broad global health engagements and improving health outcomes for populations served. Finally, we discuss WRAIR's contributions to PEPFAR priorities through use of data to drive and improve programming in real time in the era of HIV epidemic control and public health messaging that includes prevention, the 95-95-95 goals, and comorbidities.
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http://dx.doi.org/10.4269/ajtmh.20-0541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790083PMC
January 2021

Attaining 95-95-95 through Implementation Science: 15 Years of Insights and Best Practices from the Walter Reed Army Institute of Research's Implementation of the U.S. President's Emergency Plan for AIDS Relief.

Am J Trop Med Hyg 2021 01;104(1):12-25

2The Uniformed Services University of the Health Sciences, Bethesda, Maryland.

The Walter Reed Army Institute of Research (WRAIR) supports more than 350,000 people on lifesaving HIV treatment in Kenya, Nigeria, Tanzania, and Uganda through funding from the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). Here, we review and synthesize the range of impacts WRAIR's implementation science portfolio has had on PEPFAR service delivery for military and civilian populations since 2003. We also explore how investments in implementation science create institutional synergies within the U.S. Department of Defense, contributing to broad global health engagements and improving health outcomes for populations served. Finally, we discuss WRAIR's contributions to PEPFAR priorities through use of data to drive and improve programming in real time in the era of HIV epidemic control and public health messaging that includes prevention, the 95-95-95 goals, and comorbidities.
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http://dx.doi.org/10.4269/ajtmh.20-0541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790083PMC
January 2021

Impact of age on CD4 recovery and viral suppression over time among adults living with HIV who initiated antiretroviral therapy in the African Cohort Study.

AIDS Res Ther 2020 11 12;17(1):66. Epub 2020 Nov 12.

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Introduction: With increased use of antiretroviral therapy (ART), HIV mortality rates are declining and people living with HIV (PLWH) are surviving longer. We characterized CD4 recovery and viral suppression among adults aged < 50 and ≥ 50 years living with HIV who initiated ART in the African Cohort Study (AFRICOS).

Methods: Beginning in January 2013, PLWH at twelve clinics in Kenya, Uganda, Tanzania and Nigeria underwent medical history review, CD4 and viral load testing as part of the ongoing African Cohort Study (AFRICOS). ART-naïve PLWH who initiated ART within 30 days of enrollment and had at least one year of follow-up were included in these analyses. To compare ART response in participants < 50 years and ≥ 50 years old, changes in CD4 count and viral load suppression after ART initiation were examined at different time points using linear and binomial regression with generalized estimating equations. Variables for time since ART initiation and the interaction between age group and time on ART were included in the model to evaluate longitudinal changes in CD4 recovery and viral suppression by age.

Results: Between January 2013 and September 2019, 2918 PLHV were enrolled in the cohort. Of these, 443 were ART naïve and initiated on ART within 30 days of enrollment, with 90% (n = 399) aged < 50 years old at ART initiation. At ART initiation, participants aged 50 and older had a higher median CD4 count compared to participants younger than 50 years of age although it did not reach statistical significance (306 cells/mm, IQR:130-547 vs. 277cells/mm, IQR: 132-437). In adjusted models examining CD4 recovery and viral suppression there were no significant differences by age group over time. By the end of follow-up viral suppression was high among both groups of adults (96% of adults ≥ 50 years old and 92% of adults < 50 years old).

Conclusion: This study found no difference in long-term CD4 recovery or viral suppression by age at ART initiation. We found that particularly among younger adults participants had lower median CD4 counts at ART initiation, suggesting the importance of identifying and putting this population on treatment earlier in the disease course.
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http://dx.doi.org/10.1186/s12981-020-00323-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664082PMC
November 2020

Predictors of first-line antiretroviral therapy failure among adults and adolescents living with HIV/AIDS in a large prevention and treatment program in Nigeria.

AIDS Res Ther 2020 11 3;17(1):64. Epub 2020 Nov 3.

Institute of Human Virology, Federal Capital Territory, 252 Herbert Macaulay Way, Abuja, Nigeria.

Background: A substantial number of persons living with HIV (PLWH) in Nigeria do not experience durable viral suppression on first-line antiretroviral therapy (ART). Understanding risk factors for first-line treatment failure informs patient monitoring practices and distribution of limited resources for second-line regimens. We determined predictors of immunologic and virologic failures in a large ART delivery program in Abuja, Nigeria.

Methods: A retrospective cohort study was conducted at the University of Abuja Teaching Hospital, a tertiary health care facility, using data from February 2005 to December 2014 in Abuja, Nigeria. All PLWH aged ≥ 15 years who initiated ART with at least 6-month follow-up and one CD4 measurement were included. Immunologic failure was defined as a CD4 decrease to or below pre-ART level or persistent CD4 < 100 cells per mm after 6 months on ART. Virologic failure (VF) was defined as two consecutive HIV-1 RNA levels > 1000 copies/mL after at least 6 months of ART and enhanced adherence counselling. HIV drug resistance (Sanger sequences) was analyzed using the Stanford HIV database algorithm and scored for resistance to common nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Univariate and multivariate log binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs).

Results: Of 12,452 patients followed, a total of 5928 initiated ART with at least 6 months of follow-up and one CD4 measurement. The entry point for 3924 (66.2%) was through the program's own voluntary counseling and testing (VCT) center, while 1310 (22.1%) were referred from an outside clinic/program, 332 (5.6%) in-patients, and 373 (6.3%) through other entry points including prevention of mother to child transmission (PMTCT) and transferred from other programs. The mean CD4 at enrollment in care was 268 ± 23.7 cells per mm, and the mean HIV-1 RNA was 3.3 ± 1.3.log copies/mL. A total of 3468 (80.5%) received nevirapine (NVP) and 2260 (19.5%) received efavirenz (EFV)-based regimens. A total of 2140 (36.1%) received tenofovir (TDF); 2662 (44.9%) zidovudine (AZT); and 1126 (19.0%) stavudine (d4T). Among those receiving TDF, 45.0% also received emtricitabine (FTC). In a multivariate model, immunologic failure was more common among PLWH with female gender as compared to male [RR (95% CI) 1.22 (1.07-1.40)] and less common among those who entered care at the program's VCT center as compared to other entry points [0.79 (0.64-0.91)], WHO stage 3/4 as compared to 1/2 [0.19 (0.16-0.22)], or CD4 200 + cells per mm as compared to lower [0.19 (0.16-0.22)]. Virologic failure was more common among PLWH who entered care at the program's VCT center as compared to other entry points [RR (95% CI) 1.45 (1.11-1.91) and those with CD4 < 200 cells per mm at entry into care as compared to higher [1.71 (1.36-2.16)]. Of 198 patient-derived samples sequenced during virologic failure, 42 (21%) were wild-type; 145 (73%) carried NNRTI drug resistance mutations; 151 (76.3%) M184I/V; 29 (14.6%) had ≥ 3 TAMs, and 37 (18.7%) had K65R, of whom all were on TDF-containing first-line regimens.

Conclusions: In this cohort of Nigerian PLWH followed for a period of 9 years, immunologic criteria poorly predicted virologic failure. Furthermore, a subset of samples showed that patients failing ART for extended periods of time had HIV-1 strains harboring drug resistance mutations.
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http://dx.doi.org/10.1186/s12981-020-00317-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640637PMC
November 2020

Retention of a cohort of men who have sex with men and transgender women at risk for and living with HIV in Abuja and Lagos, Nigeria: a longitudinal analysis.

J Int AIDS Soc 2020 10;23 Suppl 6:e25592

Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.

Introduction: Men who have sex with men (MSM), and transgender women (TGW), face specific obstacles to retention in care, particularly in settings with stigmatization such as sub-Saharan Africa. We evaluated the impacts of HIV status and other factors on loss-to-follow-up (LTFU) and visit adherence among MSM and TGW in Abuja and Lagos, Nigeria.

Methods: TRUST/RV368 is an open cohort that provides comprehensive and integrated prevention and treatment services for HIV and sexually transmitted infections (STIs) at community venues supportive of sexual and gender minorities. Recruitment began in March 2013 and participants were followed every three months for up to 18 months. LTFU was defined as not presenting for an expected visit in the past 180 days. Visit adherence was calculated as a rate of completed visits adjusted by the number of three-month intervals elapsed since enrolment. HIV and other factors predictive of LTFU and visit adherence were evaluated using Cox proportional hazards and Poisson regression models, respectively.

Results: A total of 1447 participants who completed enrolment evaluations over two visits as of November 2018 were included in these analyses. Their median age was 24 years (interquartile range [IQR]: 21 to 28) and 53% (n = 766) were living with HIV. LTFU occurred in 56% (n = 808) and visit adherence was 0.62 (95% confidence interval: 0.61 to 0.64) visits per three-month interval. Participants at risk and living with HIV had median follow-up times of 12 months (IQR: 6 to 22), and 21 months (IQR: 12 to 30), respectively (p < 0.01). After controlling for other factors, LTFU was less common among participants living with HIV or other STIs and more common among those who did not own a cell phone, sold sex and had never undergone HIV testing prior to enrolment. These factors had parallel associations with visit adherence.

Conclusions: Retention was suboptimal in Nigerian clinics designed to serve MSM and TGW. Particularly high LTFU and low visit adherence among participants at risk for HIV could complicate deployment of HIV prevention interventions. Marketing the benefits of testing, improving access to cell phones and nurturing more trust with clients may improve retention among marginalized communities in Nigeria.
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http://dx.doi.org/10.1002/jia2.25592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527765PMC
October 2020
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