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Prior immune responses to coronaviruses might affect human SARS-CoV-2 response. We screened 2,565 serum and plasma samples collected from 2013 through early 2020, before the COVID-19 pandemic began, from 2,250 persons in 4 countries in Africa (Kenya, Nigeria, Tanzania, and Uganda) and in Thailand, including persons living with HIV-1. We detected IgG responses to SARS-CoV-2 spike (S) subunit 2 protein in 1.8% of participants. Profiling against 23 coronavirus antigens revealed that responses to S, subunit 2, or subunit 1 proteins were significantly more frequent than responses to the receptor-binding domain, S-Trimer, or nucleocapsid proteins (p0.0001). We observed similar responses in persons with or without HIV-1. Among all coronavirus antigens tested, SARS-CoV-2, SARS-CoV-1, and Middle East respiratory syndrome coronavirus antibody responses were much higher in participants from Africa than in participants from Thailand (p0.01). We noted less pronounced differences for endemic coronaviruses. Serosurveys could affect vaccine and monoclonal antibody distribution across global populations.

Depression is common during pregnancy and is associated with reduced adherence to HIV-related care, though little is known about perinatal trajectories of depression and viral suppression among women living with HIV (WLHV) in sub-Saharan Africa. We sought to assess any association between perinatal depressive symptoms and viral non-suppression among WLWH. Depressive symptomatology and viral load data were collected every 6 months from WLWH enrolled in the African Cohort Study (AFRICOS; January 2013–February 2020). Generalized estimating equations modeled associations between depressive symptoms [Center for Epidemiological Studies Depression (CES-D) ≥ 16] and viral non-suppression. Of 1722 WLWH, 248 (14.4%) had at least one pregnancy (291 total) and for 61 pregnancies (21.0%), women reported depressive symptoms (13.4% pre-conception, 7.6% pregnancy, 5.5% one-year postpartum). Depressive symptomatology was associated with increased odds of viral non-suppression (aOR 2.2; 95% CI 1.2–4.0, p = 0.011). Identification and treatment of depression among women with HIV may improve HIV outcomes for mothers.

The COVID-19 pandemic has caused significant morbidity and mortality since its emergence in December 2019. In Nigeria, the government inaugurated the Presidential Task Force on COVID-19 to coordinate resources while the Nigeria Centre for Disease Control led the public health response. The Nigeria Ministry of Defence Health Implementation Programme (MODHIP), in partnership with the US Army Medical Research Directorate - Africa/Nigeria, responded immediately to the pandemic by establishing a public health emergency operations center to coordinate the military response in support of national efforts. MODHIP has 5 functional units and 6 pillars that coordinate testing, surveillance, case management, risk communication, logistics, research, and infection prevention and control. It developed an incident action plan and each pillar had its own terms of reference to guide specific response activities while preventing duplication of efforts within the military and the Nigeria Centre for Disease Control. In addition, awareness and sensitization sessions were conducted on preventive practices for COVID-19 and infrastructure was provided for hand hygiene and screening at all military facilities. Military laboratories were configured for SARS-CoV-2 testing while selected military health facilities were equipped and designated as COVID-19 treatment centers. Research proposals aimed at better understanding the disease and controlling it were also developed. The traditional combat role of the military was redirected to complement this public health emergency response. In this article, we highlight gaps, opportunities, and lessons to improve military participation in public health emergency response in the future. More funding and multisectoral collaboration with civilian institutions are key to strengthening military public health emergency preparedness and response capabilities.

Background Introduction of antiretroviral therapy (ART) has been associated with a decline in human immunodeficiency virus (HIV)-related mortality, although HIV remains a leading cause of death in sub-Saharan Africa. We describe all-cause mortality and its predictors in people living with HIV (PLWH) in the African Cohort Study (AFRICOS). Methods AFRICOS enrolls participants with or without HIV at 12 sites in Kenya, Uganda, Tanzania, and Nigeria. Evaluations every 6 months include sociobehavioral questionnaires, medical history, physical examination, and laboratory tests. Mortality data are collected from medical records and survivor interviews. Multivariable Cox proportional hazards models were used to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for factors associated with mortality. Results From 2013 through 2020, 2724 PLWH completed at least 1 follow-up visit or experienced death. Of these 58.4% were females, 25.8% were aged ≥ 50 years, and 98.3% were ART-experienced. We observed 11.42 deaths per 1000 person-years (95% CI: 9.53–13.68) with causes ascertained in 54% of participants. Deaths were caused by malignancy (28.1%), infections (29.7%), and other non-HIV related conditions. Predictors of mortality included CD4 ≤ 350 cells/µL (aHR 2.01 [95% CI: 1.31–3.08]), a log10copies/mL increase of viral load (aHR 1.36 [95% CI: 1.22–1.51]), recent fever (aHR 1.85[95% CI: 1.22–2.81]), body mass index Conclusions The mortality rate was low in this cohort of mostly virally suppressed PLWH. Patterns of deaths and identified predictors suggest multiple targets for interventions to reduce mortality.

Background Multi-month dispensing (MMD) of antiretroviral therapy (ART) decreases logistical burdens on HIV clinics and patients, which is especially important during the COVID-19 pandemic. HIV programs are scaling-up 6-month dispensing (6MD), but the impact on viral suppression (VS) has not been well-documented in programmatic settings. Methods The African Cohort Study (AFRICOS) is an international observational study of people living with HIV (PLWH) receiving HIV care. In Nigeria and Kenya, this includes 6MD. Participants undergo semiannual viral load quantification and were included in analysis if they had complete data, documentation of MMD (self-reported) and at least two follow-up visits after initiating MMD. In stratified analyses for each country, we used multivariable logistic regression with generalized estimating equations to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) comparing VS < 50 copies/mL among those who received 6MD to those given 3-5 months dispensing (3-5MD) of ART. Analyses were adjusted for age, education, employment, distance to clinic, duration on ART, ART regimen (TLD vs other) and self-reported ART adherence (≥ 1 missed dose in past 30 days). Results Between January 30, 2020, when MMD data was first collected, and September 1, 2021, 1176 PLWH in Kenya and 272 in Nigeria had at least one visit; 285 participants from Kenya, totaling 442 visits, and 177 participants from Nigeria, totaling 382 visits, met criteria and were included in analysis. At most recent visit, VS < 50 copies/mL was documented in 266 (93.3%) participants from Kenya and 125 (70.6%) participants from Nigeria. Among the 35 participants given 6MD in Kenya, compared to 250 participants given 3-5MD, the aOR for VS was 0.42 (95%CI: 0.13-1.37); among the 91 participants given 6MD in Nigeria, compared to the 86 participants given 3-5MD, the aOR was 3.01 (95%CI: 1.70-5.31). Conclusion The positive association between 6MD and VLS in Nigeria, as compared to 3-5MD, should prompt more aggressive scale-up of 6MD. The lack of an association in Kenya merits further investigation, but likely relates to high overall VS and few participants on 6MD. Updated data from specific geographic and demographic sub-populations is needed to inform programming as 6MD is scaled. Disclosures All Authors: No reported disclosures.

Background Pre-exposure prophylaxis (PrEP) is an essential component to stopping the HIV epidemic. Recent breakthroughs in PrEP including the vaginal ring and long-acting preparations provide more options for individuals. However, PrEP uptake continues to be a challenge. We evaluated PrEP awareness and barriers to PrEP uptake among individuals in four sub-Saharan African countries. Methods Individuals aged 16 years or older without HIV were referred to the African Cohort Study (AFRICOS) at 12 PEPFAR-supported clinics in Uganda, Kenya, Tanzania and Nigeria through their sexual partners, social media outlets or outreach to communities and schools. Starting in 2020, participants were administered a survey regarding PrEP knowledge, practices, and beliefs every six months. We conducted descriptive analyses from a participant’s first study visit after PrEP-related questions had been introduced. Results From February 2020 to November 2021, the PrEP survey was completed by 372 participants, of whom 204 (55%) were female; their median age was 37.5 (interquartile range (IQR): 26.6-46.5) years old; 228 (61%) were married; 64 (17%) consumed alcohol and 6 (2%) used recreational drugs. Of the 314 (92%) who reported ever having sex, the median age at sexual debut was 18 (IQR: 16-19); 241 (77%) reported 1 regular partner; 295 (94%) had no casual partners in the past six months, 97 (31%) had an HIV+ partner and 26 (10%) had a partner with an unknown HIV status. Results from the PrEP survey are in the Figure. When asked about PrEP, 44 (29%) had discussed PrEP with their provider and 73 (20%) stated they would feel ashamed or embarrassed taking PrEP. Those who had heard of PrEP were more likely to be unmarried (p=0.046) and more likely not to have used a condom during the last sexual encounter with their regular partner (p< 0.05). PrEP knowledge and practices Conclusion In our cohort, few participants had heard of or were taking PrEP. While our cohort may not represent a high-risk population, PrEP awareness was limited among those who were either unaware of their partner’s status or who had a partner infected with HIV. The lack of PrEP awareness highlights the need for increased provider education and outreach especially as new, and potentially less stigmatizing, PrEP options come to market. Disclosures All Authors: No reported disclosures.

Cervical cancer is a common preventable cancer among African women living with HIV (WLWH). Molecular diagnostics for high-risk human papillomavirus (HR-HPV) genotypes are standard components of cervical cancer screening in resource-rich countries but not in resource-limited settings. We evaluated HR-HPV genotypes among women with and without HIV in four African countries to inform cervical cancer preventive strategies.The African Cohort Study (AFRICOS) enrolled participants with and without HIV at 12 clinics in Tanzania, Kenya, Uganda and Nigeria. Cervical cytobrush specimens from women were genotyped for 14 HR-HPV types using the multiplex Seegene Anyplex real-time PCR assay. Robust Poisson regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for factors associated with HR-HPV in WLWH.From January 2015 to March 2020, 868 WLWH and 134 WLWoH were tested for HR-HPV with prevalence of 50.9% and 38.1%, respectively (p = 0.007). Among WLWH, 844 (97.4%) were ART-experienced and 772 (89.7%) virally suppressed ≦1000 copies/mL. The most frequent HR-HPV types among WLWH were HPV-16 (13.5%), HPV-52 (9.5%) and HPV-35 (9.3%). HR-HPV infection was more common among Tanzanian WLWH (adjusted RR: 1.23, 95% CI: 1.05-1.44, p = 0.012). Also, WLWH with CD4 T cells of200 cell/mm 3 had 1.51-fold increased risk of having HR-HPV (95% CI: 1.23-1.86, p 0.001).HR-HPV was common in WLWH in four African countries, particularly among women with low CD4. Scale up of HPV vaccines and development of vaccines with broader activity against less common HR-HPV types may improve cervical cancer prevention in Africa.

Non-communicable diseases (NCDs) are an important driver of morbidity among ageing people living with HIV (PLWH). We examined the composite role of age and HIV status on NCDs in people living with and without HIV.The African Cohort Study (AFRICOS) prospectively enrols participants aged ≥15 years with and without HIV at 12 sites in Kenya, Tanzania, Uganda and Nigeria. From 21 January 2013 to 1 September 2021, we assessed participants for renal insufficiency (estimated glomerular filtration rate60 ml/minute/1.73 mOf 3761 participants with age data, 557 (14.8%) were age ≥50, 2188 (58.2%) were females and 3099 (82.4%) were PLWH. At enrolment, the prevalence of elevated BP, dysglycemia, renal insufficiency and obesity were n = 128 (26.9%), n = 75 (15.8%), n = 8 (1.7%) and n = 40 (8.4%), respectively, for PLWH ≥50. Compared to people without HIV age50, PLWH age ≥50 had increased adjusted odds of having DM (OR: 2.78, 95% CI: 1.49-5.16), dysglycemia (OR: 1.98, 95% CI: 1.51-2.61) and renal insufficiency (OR: 6.20, 95% CI: 2.31-16.66). There were significant differences by study site, specifically, participants from Nigeria had the highest odds of elevated BP, dysglycemia and renal insufficiency as compared to Uganda.There was a high burden of NCDs in this African cohort with differences by geographic region. In order to promote healthy ageing with HIV, screening and treatment for common NCDs should be incorporated into routine HIV care with attention paid to geographic heterogeneity to better allocate resources.

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 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.

Ophthalmic disease in people living with HIV (PLWH) and at-risk controls in Sub-Saharan Africa was evaluated. PLWH were more likely to have ophthalmic disease at enrollment, but there was no difference in incidence once enrolled.

The coronavirus disease 2019 (COVID-19) pandemic and associated public health responses have disrupted daily living activities with economic and health consequences globally. We observed transient decreases in human immunodeficiency virus (HIV) clinic visit adherence and food security among persons living with HIV early in the pandemic, and an increase in viral suppression later in the pandemic.

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.

Background Emerging HIV drug resistance (HIVDR) could jeopardize the success of standardized HIV management protocols in resource-limited settings. We characterized HIVDR among antiretroviral therapy (ART)-naive and experienced participants in the African Cohort Study (AFRICOS). Methods From January 2013 to April 2019, adults with HIV-1 RNA >1000 copies/mL underwent ART history review and HIVDR testing upon enrollment at 12 clinics in Uganda, Kenya, Tanzania, and Nigeria. We calculated resistance scores for specific drugs and tallied major mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) using Stanford HIVDB 8.8 and SmartGene IDNS software. For ART-naive participants, World Health Organization surveillance drug resistance mutations (SDRMs) were noted. Results HIVDR testing was performed on 972 participants with median age 35.7 (interquartile range [IQR] 29.7–42.7) years and median CD4 295 (IQR 148–478) cells/mm3. Among 801 ART-naive participants, the prevalence of SDRMs was 11.0%, NNRTI mutations 8.2%, NRTI mutations 4.7%, and PI mutations 0.4%. Among 171 viremic ART-experienced participants, NNRTI mutation prevalence was 83.6%, NRTI 67.8%, and PI 1.8%. There were 90 ART-experienced participants with resistance to both efavirenz and lamivudine, 33 (36.7%) of whom were still prescribed these drugs. There were 10 with resistance to both tenofovir and lamivudine, 8 (80.0%) of whom were prescribed these drugs. Conclusions Participants on failing ART regimens had a high burden of HIVDR that potentially limited the efficacy of standardized first- and second-line regimens. Management strategies that emphasize adherence counseling while delaying ART switch may promote drug resistance and should be reconsidered., From 2013–2019, pretreatment drug resistance has increased in Uganda, Kenya, Tanzania, and Nigeria. Resistance was observed in most treatment-experienced participants on failing regimens, some of whom had mutations that could compromise standard first- and second-line regimen efficacy.

Introduction In 2019, the World Health Organization (WHO) recommended tenofovir disoproxil fumarate-lamivudine-dolutegravir (TLD) as the preferred first line regimen for adults and adolescents regardless of childbearing status. Nevertheless, final eligibility is determined by local policies which may vary from WHO recommendations. We examined TLD transition by gender across five PEPFAR-supported HIV care programs in sub-Saharan Africa. Methods The African Cohort Study (AFRICOS) enrolls people living with HIV (PLWH) engaged in care in Uganda, Kenya (South Rift Valley and Kisumu West), Tanzania and Nigeria. PLWH with at least one study visit after the country introduced TLD were included. We generated Kaplan-Meier (KM) curves to compare TLD transition by gender from 1) time countries’ introduction of TLD and 2) time of TLD eligibility according to local policies. Results Among 2.476 participants enrolled through September 2021 at 4 sites in sub-Saharan Africa and eligible to transition to TLD, fewer women (68%) compared to men (80%, p Conclusions Despite TLD being the WHO’s preferred regimen since 2019, transition of women to potentially lifesaving TLD has been slower than men at certain clinical sites even after accounting for local eligibility criteria.

Dolutegravir (DTG) has become a preferred component of first-line antiretroviral therapy (ART) in many settings but may be associated with excess weight gain. We evaluated changes in weight and body mass index (BMI) after switch to single-tablet tenofovir/lamivudine/dolutegravir (TLD) by people living with HIV (PLWH) in four African countries.The African Cohort Study (AFRICOS) prospectively follows adults with and without HIV in Kenya, Uganda, Tanzania and Nigeria. Demographics, ART regimen, weight, BMI and waist-to-hip ratio were collected every 6 months. Multivariable Cox proportional hazards modelling was used to estimate hazard ratios and 95% confidence intervals (CIs) for factors associated with developing a BMI ≥25 kg/mFrom 23 January 2013 to 1 December 2020, 2950 PLWH were enrolled in AFRICOS and 1474 transitioned to TLD. In adjusted models, PLWH on TLD had 1.77 times the hazard of developing a high BMI (95% CI: 1.22-2.55) compared to PLWH on non-TLD ART. Examining change in weight among all PLWH on ART, participants on TLD gained an average of 0.68 kg (95% CI: 0.32-1.04) more than PLWH on other regimens after adjusting for duration on ART, sex, age, study site and CD4 nadir. Among participants who switched to TLD, the average change in weight prior to TLD switch was 0.35 kg/year (95% CI: 0.25-0.46) and average change in weight was 1.46 kg/year (95% CI: 1.18-1.75) in the year following transition to TLD after adjustment for confounders.Elevated BMI and weight gain among PLWH on TLD are concerning safety signals. Implications for the development of metabolic comorbidities should be monitored, particularly if annual weight gain persists during continued follow-up after transitioning to TLD.

The lifespan of people living with HIV is increasing, and non-communicable diseases (NCDs) are becoming an important driver of morbidity in this population. We examined the prevalence of NCDs in older people with HIV and factors associated with development of NCDs.The African Cohort Study is a prospective cohort enrolling adults with and without HIV at 12 sites in Kenya, Tanzania, Uganda, and Nigeria. Using data collected from Jan 21, 2013 to June 30, 2021, we assessed the prevalence and odds of NCDs, including renal insufficiency (estimated glomerular filtration rate [GFR]60 mL/min/1·73 m²), elevated blood pressure (any systolic blood pressure139 mm Hg or diastolic BP89 mm Hg), obesity (body mass index30), diabetes (fasting glucose ≥126 mg/dL or receiving medication for diabetes) or hyperglycaemia (fasting glucose ≥99 mg/dL or non-fasting ≥199 mg/dL). Diabetes and hyperglycaemia were collectively evaluated as dysglycaemia. We used multivariable logistic regression with generalised estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with NCDs. Diabetes and hyperglycaemia models were adjusted for potential confounders including study site and sex. Renal insufficiency models had similar adjustments with the addition of elevated blood pressure and hyperglycaemia.Of 3434 participants, 2003 (59·3%) were female and 1431 (40·7%) were male, and 2949 (85·9%) were living with HIV. Of people living with HIV, 2188 (74·2%) were younger than 50 years and 761 (25·8%) were aged 50 years or older. Among people living with HIV aged 50 or older, 27·5% (n=209 had elevated blood pressure, 13·4% (102) had dysglycaemia, 4·3% (33) had renal insufficiency, and 11·7% (89) had obesity at last visit. Compared with people without HIV under 50, people living with HIV aged 50 or older had increased adjusted odds of having diabetes (5·29, 95% CI 2·61-10·70), hyperglycaemia (1·86, 1·38-2·50), and renal insufficiency (6·37, 2·38-17·1). We found no differences between individuals aged 50 years or older with and without HIV for diabetes, hyperglycaemia, and renal insufficiency.There was a high burden of NCDs in this cohort. HIV status was not associated with NCD prevalence, although the study was probably underpowered to detect such an association. Screening and treatment for common NCDs, such as raised blood pressure and dysglycaemia, should be considered as part of HIV integrated care. Such an approach might help to prevent other NCDs, such as renal insufficiency, and improve the span of healthy life.PEPFAR via cooperative agreements between HJF and the US Department of Defense.

The real-world impact on viral suppression of switching from non-dolutegravir-based therapy to tenofovir/lamivudine/dolutegravir (TLD) is not thoroughly characterized in Africa. We described the virologic consequences of switching regimens in the African Cohort Study (AFRICOS), an observational cohort in Nigeria, Kenya, Uganda, and Tanzania.Among antiretroviral-experienced people living with HIV (PLWH) in AFRICOS, we compared viral load (VL) nonsuppression (VL ≥ 1000 copies/mL) among those who switched with those who never switched to TLD, restricting to participants who had at least 1 visit with a recorded VL after the countrywide rollout of TLD. We calculated Kaplan-Meier curves and conducted Cox proportional hazards modeling to estimate adjusted hazard ratios and 95% confidence intervals for factors potentially associated with nonsuppression.As of September 1, 2021, there were 3108 PLWH enrolled. Among 1576 participants who switched to TLD, 1486 (94.3%) remained suppressed after transition, 12 (0.8%) remained unsuppressed, and 38 (2.4%) lost suppression, compared with 652 (82.1%), 75 (9.4%), and 46 (5.8%), respectively, of 797 participants who did not switch ( P0.001). After adjustment for sex, age, study site, and self-reported antiretroviral therapy adherence, virally suppressed participants who did not switch to TLD had significantly higher rates of losing viral suppression compared with those who switched (adjusted hazard ratio: 4.26; 95% confidence interval: 2.72 to 6.68).PLWH transitioning to TLD had higher rates of viral suppression compared with those who remained on other regimens. Even within a highly suppressed population, TLD transition provided significant benefits for achieving or maintaining viral suppression.

Background: A significant minority of people living with HIV (PLWH) achieve viral suppression (VS) on antiretroviral therapy (ART) but do not regain healthy CD4 counts. Clinical factors affecting this immune non-response (INR) and its effect on incident serious non-AIDS events (SNAEs) have been challenging to understand due to confounders that are difficult to control in many study settings. Setting: The U.S. Military HIV Natural History Study (NHS) and African Cohort Study (AFRICOS). Methods: PLWH with sustained VS (Results: INR prevalence was 10.8% and 25.8% in NHS and AFRICOS, respectively. Higher CD4 nadir was associated with decreased odds of INR (aOR=0.31 [95% CI: 0.26, 0.37] and aOR=0.50 [95% CI: 0.43, 0.58] per 100 cells/µl in NHS and AFRICOS, respectively). After adjustment, INR was associated with a 61% increase in relative risk of SNAE [95% CI: 1.12, 2.33]. Probability of "SNAE-free" survival at 15 years since sustained VS was approximately 20% lower comparing those with and without INR; nearly equal to the differences observed by 15-year age groups. Conclusion: CD4 monitoring before and after VS is achieved can help identify PLWH at risk for INR. INR may be a useful clinical indicator of future risk for SNAEs.

Background Increased availability of HIV care over the past decade has dramatically reduced morbidity and mortality among people living with HIV (PLWH) in sub-Saharan Africa. However, perceived and experienced barriers to care, including dissatisfaction with services, may impact adherence and viral suppression. We examined the associations between satisfaction with HIV care and antiretroviral therapy (ART) adherence and viral load suppression. Methods The African Cohort Study (AFRICOS) is a prospective observational study conducted at PEPFAR-supported clinics in four African countries. At enrollment and twice-yearly study visits, participants received a clinical assessment and a socio-behavioral questionnaire was administered. Participants were classified as dissatisfied with care if they reported dissatisfaction with any of the following: waiting time, health care worker skills, health care worker attitudes, quality of clinic building, or overall quality of care received. Robust Poisson regression was used to estimate prevalence ratios and 95% confidence intervals (CIs) for associations between satisfaction with care and ART adherence and between satisfaction with care and viral suppression (viral load Results As of 1 March 2020, 2928 PLWH were enrolled and 2311 had a year of follow-up visits. At the first annual follow-up visit, 2309 participants responded to questions regarding satisfaction with quality of care, and 2069 (89.6%) reported satisfaction with care. Dissatisfaction with waiting time was reported by 177 (7.6%), building quality by 59 (2.6%), overall quality of care by 18 (0.8%), health care worker attitudes by 16 (0.7%), and health care worker skills by 15 (0.7%). After adjusting for age and site, there was no significant difference in viral suppression between those who were satisfied with care and those who were dissatisfied (aPR: 1.03, 95% CI 0.97–1.09). Satisfaction with HIV care was moderately associated with ART adherence among AFRICOS participants (aPR: 1.09; 95% CI 1.00–1.16). Conclusions While patient satisfaction in AFRICOS was high and the association between perceived quality of care and adherence to ART was marginal, we did identify potential target areas for HIV care improvement, including reducing clinic waiting times.

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.

In a retrospective review of hospital records of 40 human monkeypox cases from Nigeria, the majority developed fever and self-limiting vesiculopustular skin eruptions. Five deaths were reported. Compared to human immunodeficiency virus (HIV)–negative cases, HIV type 1–coinfected cases had more prolonged illness, larger lesions, and higher rates of both secondary bacterial skin infections and genital ulcers.

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 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 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.

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. WLWH45 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.

Washington, DC, and sub-Saharan Africa are both affected by generalized HIV epidemics. However, care for persons living with HIV (PLWH) and clinical outcomes may differ in these geographically and culturally diverse areas. We compared patient and clinical site characteristics among adult persons living with HIV (PLWH) enrolled in two longitudinal HIV cohort studies-the African Cohort Study (AFRICOS) and the DC Cohort.The DC Cohort is a clinic-based city-wide longitudinal cohort comprised of PLWH attending 15 HIV clinics in Washington, DC. Patients' socio-demographic characteristics, clinical evaluations, and laboratory data are retrospectively collected from electronic medical records and limited manual chart abstraction. AFRICOS is a prospective observational cohort of PLWH and uninfected volunteers attending 12 select HIV care and treatment facilities in Nigeria, Kenya, Uganda and Tanzania. AFRICOS study participants are a subset of clinic patients who complete protocol-specific visits every 6 months with history and physical examination, questionnaire administration, and blood/sputum collection for ascertainment of HIV outcomes and comorbidities, and neurocognitive and functional assessments. Among participants aged ≥ 18 years, we generated descriptive statistics for demographic and clinical characteristics at enrollment and follow up and compared them using bivariable analyses.The study sample included 2,774 AFRICOS and 8,420 DC Cohort participants who enrolled from January 2013 (AFRICOS)/January 2011 (DC Cohort) through March 2018. AFRICOS participants were significantly more likely to be women (58.8% vs 27.1%) and younger (83.3% vs 61.1% aged50 years old) and significantly less likely to be MSM (only 0.1% of AFRICOS population reported MSM risk factor) than DC Cohort. Similar rates of current viral suppression (about 75% of both samples), hypertension, hepatitis B coinfection and alcohol use were observed. However, AFRICOS participants had significantly higher rates of CD4200 and tuberculosis and significantly lower rates of obesity, DM, hepatitis C coinfection and syphilis.With similar viral suppression outcomes, but many differences between our cohorts noted, the combined sample provides unique opportunities to assess and compare HIV care and treatment outcomes in the U.S. and sub-Saharan Africa. Comparing these two cohorts may inform care and treatment practices and may pave the way for future pathophysiologic analyses.

Viral hemorrhagic fevers (VHFs) remain some of the most devastating human diseases, and recent outbreaks of Ebola virus disease (EVD) 1,2 and Lassa fever (LF) 3,4 highlight the urgent need for sensitive, field-deployable tests to diagnose them 5,6. Here we develop CRISPR-Cas13a-based (SHERLOCK) diagnostics targeting Ebola virus (EBOV) and Lassa virus (LASV), with both fluorescent and lateral flow readouts. We demonstrate on laboratory and clinical samples the sensitivity of these assays and the capacity of the SHERLOCK platform to handle virus-specific diagnostic challenges. Our EBOV diagnostic detects both the L and NP genes, thereby eliminating the potential for false positive results caused by the rVSVΔG-ZEBOV-GP live attenuated vaccine. Our two LASV diagnostics together capture 90% of known viral diversity and demonstrate that CRISPR-RNAs (crRNAs) can be effectively multiplexed to provide greater coverage of known viral diversity. We performed safety testing to demonstrate the efficacy of our HUDSON protocol in heat-inactivating and chemically treating VHF viruses before SHERLOCK testing, eliminating the need for an extraction. We developed a user-friendly field protocol and mobile application (HandLens) to report results, facilitating SHERLOCK’s use in endemic regions. Finally, we successfully deployed our tests in Sierra Leone and Nigeria in response to recent outbreaks.

Consistent condom use is an inexpensive and efficacious HIV prevention strategy. Understanding factors associated with condom use and barriers to use can inform strategies to increase condom uptake. The ongoing African Cohort Study prospectively enrolls adults at 12 clinical sites in Uganda, Kenya, Tanzania, and Nigeria. At enrollment, participants are asked about condom use at last sex with a regular partner. Robust Poisson regression models were used to evaluate predictors of self-reported condom use. Participants who reported not using condoms were asked to provide reasons. From January 2013 to September 2019, 2482 participants reported having at least one regular sexual partner in the preceding 6 months. Of those, 1577 (63.5%) reported using a condom at last sex. Condom use was more common among older participants, males, HIV-infected participants, and those with an HIV-infected partner. Married participants, those with a partner of unknown HIV status, and those reporting alcohol use were less likely to report condom use at last sex. Condom use at last sex also varied significantly by clinical site. Partner disapproval or refusal to use a condom was a consistent driver of disparities in condom use among participants who were HIV infected, female, and aged 18-24 years. Effective HIV prevention programs should integrate condom education with the tools necessary to negotiate condom use with regular partners.

Extended Spectrum Beta Lactamase (ESBL) producing Escherichia coli is a global cause of life threatening infections. We determined the presence of ESBL and carbapenemase production in clinical isolates of E. coli and their antibiotic susceptibility. Clinical isolates of community and hospital acquired E. coli from 220 patients seen at a tertiary hospital were evaluated. Antibiotic susceptibility testing was by the modified Kirby-Bauer protocol while ESBL production was determined by the Double Disk Synergy Test (DDST). Carbapenem resistance was confirmed by the Modified Hodge Test. Of the 220 isolates, 122 (55.5%) were from females; 41 (18.6%) were ESBL positive. About 90% of the ESBL producing isolates were resistant to nine of the 15 antimicrobial agents tested. However, only one (2.4%) of the 41 ESBL producing isolates exhibited carbapenem resistance. The ESBL negative isolates were susceptible to Meropenem (100%), Cefepime (97.8%), Ceftriaxone (96.6%) and Cefotaxime (96.6%). All the ESBL producing isolates harbored detectable plasmids with sizes ranging from 2322 to 23,130 base pairs. Our findings show that although multidrug resistant ESBL producing E. coli are prevalent in both the hospital and the community in this environment, carbapenem resistance is still low. We recommend that institutions develop guidelines for the early phenotypic detection of ESBLs and carbapenem resistance.

Background Ebola Virus Disease (EVD) outbreaks primarily occur in the HIV endemic setting of Sub-Saharan Africa. Transient increases in HIV viral load (VL), or blips, have been described following routine vaccinations. We characterized VL blips among PLWH enrolled in a phase 2 trial of a heterologous two-dose EVD vaccine. Methods In EBL2003, adult participants with and without HIV were randomized 1:4 to receive placebo or vaccine. Part A in the US studied MVA-BN-Filo followed by Ad26.ZEBOV 14 days later. Part B in Africa evaluated this MVA/Ad26 regimen and also a schedule of Ad26.ZEBOV followed by MVA-BN-Filo 29 days later. VL was assessed at screening, pre-vaccination, and 21, 42, 180, and 365 days post dose 2. Participants with VL < 20 copies/mL at the first 2 visits who received both doses and had complete VL data through 42 days post dose 2 were evaluated. Blips were defined as a post-injection VL ≥ 20 copies/mL no later than 42 days post dose 2, with subsequent return to VL < 20 copies/mL. Results A total of 277 PLWH on antiretroviral therapy (ART) were assessed; 73.3% (203) had baseline virologic suppression, and 89.2% (181) of those received both doses with complete VL data for inclusion in the analysis. Overall, 19.9% (36) experienced blips: 20.0% (29) of vaccinees vs 19.4% (7) of placebo recipients (p=1.0). All baseline suppressed participants with post-injection viremia subsequently regained suppression. Among vaccinees, the mean blip VL was 192 copies/mL, and the mean blip duration was 56 days, which was not significantly different from placebo. Of all blips, only 2 were > 1,000 copies/mL. Blips occurred in 24.0% (25) of Ad26/MVA recipients, and 9.7% (4) of MVA/Ad26 recipients (p=0.07). A dose of Ad26 was associated with a blip in 6.9% (10) of recipients vs 13.1% (19) for MVA recipients (p=0.12). Regardless of regimen, dose 1 was associated with a blip in 8.3% (12) of vaccinees, compared to 11.7% (17) of vaccinees for dose 2 (p=0.43). Conclusion Among successfully treated PLWH, we observed low magnitude post-dose HIV blips that were not more common in vaccine vs. placebo recipients and did not result in loss of virologic suppression. This data is favorable for the deployment of the EVD vaccines in this trial in areas of high HIV endemicity. Disclosures Benjamin L. Custer, M.D., Alexion Pharmaceuticals (Shareholder)Armata Pharmaceuticals (Shareholder)Biomarin Pharmaceutical (Shareholder)Crispr Therapeutics (Shareholder)CVS Health Corp (Shareholder)Editas Medicine (Shareholder)Gilead (Shareholder)Glaxo Smith Kline (Shareholder)Hologic Inc (Shareholder)Merck (Shareholder)Mesoblast LTD (Shareholder)Pfizer (Shareholder)Sanofi (Shareholder)Unitedhealth Group (Shareholder)Vertex Pharmaceuticals (Shareholder) Georgi Shukarev, MD, Janssen (Employee) Auguste Gaddah, PhD, Janssen Pharmaceutica N.V (Employee) Kerstin Luhn, PhD, Janssen Vaccines and Prevention (Employee, Shareholder) Macaya Douoguih, MD, MPH, Janssen (Employee) Cynthia Robinson, MD, Janssen Vaccines (Employee)

Background Each year, 6 million new syphilis cases are diagnosed globally. Seroprevalence studies in low-income countries (LIC) are limited but is estimated at 3.5-4.6%. Few studies have researched prevalence of sexually transmitted infections (STIs) in people living with human immunodeficiency virus (HIV; PLWH). Current guidelines for PLWH in LIC recommend STI testing for symptomatic persons and those with a new HIV diagnosis, which may lead to high rates of undiagnosed STIs. Here we provide updated STI prevalence rates and risk factors for syphilis co-infection in PLWH in the African Cohort Study (AFRICOS). Methods AFRICOS is an ongoing longitudinal study enrolling PLWH in four African countries where participants undergo routine medical exams, sociobehavioral questionnaires, and laboratory extraction for study purposes every 6 months. Enrollment syphilis data was extracted to determine screen-positive and serologically-confirmed syphilis prevalence rates for this study. Bivariate and multivariate analysis were performed to determine risk factors for HIV and syphilis co-infection and reported as adjusted prevalence ratios (APR) with 95% confidence intervals (CI). Results Between January 2013 and March 1, 2020, 2883 PLWH enrolled. Prevalence of screen-positive and confirmed syphilis was 5.2% and 3%, respectively. Among PLWH with confirmed syphilis, 58.6% were women, mean age was 37.8 years old (IQR 31.658, 45.011, p = 0.068), and genital ulcers were documented in 1.61% participants. In the multivariate model, participants with confirmed syphilis co-infection were more likely to have none or some primary education [2.65 (1.34, 5.230)], demonstrate impaired cognition [2.1 (1.25, 3.590], and consume alcohol [1.88 (1.19, 2.970] compared to those without syphilis. Conclusion In conclusion, our findings suggest that syphilis rates remain elevated at endemic levels in LIC where diagnosis remains challenging. Based on our analysis, current STI guidelines for PLWH in Africa are likely leading to a large proportion of undiagnosed STIs and potentially contributing to community spread. While this study observed that lower education level, alcoholism, and impaired cognition were associated with syphilis co-infection, further studies are needed to investigate these associations. Disclosures All Authors: No reported disclosures

Background In the “test and treat” era, early ART may decrease the prevalence of advanced HIV disease (AHD), defined as having a CD4 cell count < 200 cells/µL or World Health Organization (WHO) clinical stage III or IV disease. We assessed trends in AHD and ART coverage and describe factors associated with AHD among adults living with HIV (LWH) across four countries before and during the “test and treat” era. Methods The African Cohort Study (AFRICOS) is a prospective cohort enrolling adults at risk for HIV or LWH from 12 facilities in Uganda, Kenya, Tanzania and Nigeria. Clinical history review and laboratory testing were performed at enrollment and every 6 months. Serum cryptococcal antigen screening (CrAg) was performed in a subset with CD4 < 200 at enrollment. Logistic regression was used to estimate odds ratios for factors associated with CD4 < 200. Results From January 2013–December 2019, 2934 adults LWH were enrolled (median age 38 years [interquartile range, 31–46 years], 41.5% men). Of 2903 with CD4 results at enrollment, 567 (19.5%) had CD4 < 200. Despite consistent increases in ART coverage since 2016, across all countries the prevalence of AHD did not decline below levels observed in 2013 until 2019. The prevalence of CD4 < 200 did not significantly decline from 11.9% (range 9.1–25.0%) in 2013 to 10.3% (range 0–16%) in 2019, p=0.7, while ART coverage increased from 74.7% (range 68.3–93.8%) in 2013 to 97.5% (range 86–100%) in 2019, p= < 0.01 (Figure 1). Factors associated with a higher risk of CD4 < 200 at enrollment were being enrolled in Tanzania, male sex, age >29 years, having a primary or some secondary education or above, and WHO stage II disease or higher. Factors associated with a lower risk of CD4 < 200 were >1 year since HIV diagnosis and being on ART for at least 6 months (Table 1). Among those with CD4 < 200 at enrollment, the most commonly reported comorbidities included HIV wasting syndrome (9.3%) and tuberculosis (TB) (2.3%); 19 (3.4%) of 564 adults screened were CrAg positive. Figure 1: Trends in Percentage of Participants with CD4 Table 1: Factors associated with CD4 Conclusion Despite the scale-up of ART in the era of “test and treat”, AHD prevalence has only recently trended downward. Continued efforts towards early HIV diagnosis and timely ART initiation are needed to reduce the risk for CD4< 200. Strategies to increase TB screening, prophylaxis, and treatment are essential to reduce morbidity. Disclosures All Authors: No reported disclosures

Background Global reduction in new infant HIV infections is largely due to the expansion of prevention of mother-to-child transmission (PMTCT) programs. Identification of gaps in healthcare services is paramount in targeting interventions that identify high-risk populations and healthcare barriers that could lead to increased risk of mother to child transmission (MTCT) of HIV. Methods HIV infected women from 5 regions of Africa enrolled in the African Cohort Study (AFRICOS) were followed prospectively with assessments performed every 6 months. Sociodemographic factors, pregnancy outcomes, and access of PMTCT resources were reviewed for retrospectively reported pregnancies and those followed prospectively from study enrollment. Statistical analysis compared the impact of clinical factors on infant mortality and preterm delivery. Results The study reported 5591 pregnancies from January 2013 to June 2019 of which 5363 were retrospectively reported prior to study enrollment and 228 occurred after enrollment. Pregnancies followed prospectively had higher rates of linkage to PMTCT services prenatally (92.5% vs 6.8%, P< 0.001), intrapartum (64.5% vs 3.5%, P< 0.001), and post-partum (64.5% vs 2.9%, P< 0.001). This group had higher rates of delivery by a skilled birth attendant (93.4% vs 66.7%, P< 0.001) and antiretroviral therapy (ART) prescribed antepartum (96.1% vs 5.5%, P< 0.001) and post-partum (74.6% vs 3.6%, P< 0.001). Both groups had similar rates of prescriptions for intrapartum ART (98.7% vs 97.9%). The majority of women reported ART adherence (96.5%, P< 0.001) which was associated with a decrease in both preterm delivery and infant mortality (adjusted OR 0.24, 95% CI 0.15-0.39). A significant proportion of women followed prospectively reported their infants received ART with good adherence (51.8% vs 0.3% and 93.4% vs 6.3%, respectively P< 0.001). Conclusion Participation in AFRICOS increased linkage to PMTCT programs which resulted in increased likelihood of skilled delivery and appropriate ART use for women and their infants. It highlights that linkage to care continues to be a crucial factor in limiting MTCT of HIV especially in resource-limited settings. Limitations in this study exist due to the low number of prospectively followed pregnancies. Disclosures All Authors: No reported disclosures

Lassa virus (LASV) causes Lassa fever (LF), a viral hemorrhagic fever endemic in West Africa. LASV strains are clustered into six lineages according to their geographic location. To confirm a diagnosis of LF, a laboratory test is required. Here, a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay using a portable device for the detection of LASV in southeast and south-central Nigeria using three primer sets specific for strains clustered in lineage II was developed. The assay detected in vitro transcribed LASV RNAs within 23 min and was further evaluated for detection in 73 plasma collected from suspected LF patients admitted into two health settings in southern Nigeria. The clinical evaluation using the conventional RT-PCR as the reference test revealed a sensitivity of 50% in general with 100% for samples with a viral titer of 9500 genome equivalent copies (geq)/mL and higher. The detection limit was estimated to be 4214 geq/mL. The assay showed 98% specificity with no cross-reactivity to other viruses which cause similar symptoms. These results suggest that this RT-LAMP assay is a useful molecular diagnostic test for LF during the acute phase, contributing to early patient management, while using a convenient device for field deployment and in resource-poor settings.

Lassa fever is a viral haemorrhagic fever endemic in West Africa, especially in: Guinea, Liberia, Nigeria and Sierra Leone. It is transmitted by the multimammate rat Mastomy natalensis, though additional rodent reservoir may contribute to infections. The virus was first identified in 1969 in the town of Lassa, North-East Nigeria from where it derived its name. Since then, several epidemics have occurred in endemic communities, including recent outbreaks with higher fatalities. There is evidence of expanding epidemiology within Africa, imported cases in Europe and North America, and potential for bioterrorism remains a global concern. In this Chapter, we describe the epidemiology and management of Lassa fever in the West African sub-region with a focus on overcoming the socio-cultural challenges. In memory of several healthcare workers who have lost their lives while providing care for Lassa fever patients, we start with a case vignette that describes the confusion and sadness the disease and its complications often bring. The chapter then goes on to discuss the epidemiology, virology, pathogenesis, clinical and laboratory characteristics of the disease with a highlight of the sociocultural challenges that perpetuate the epidemics of Lassa fever in most endemic communities 50 years after its characterisation. The chapter ends with suggestions on how to improve surveillance, prevention and control.

Background: Electrocardiogram (ECG) is a simple, readily affordable, and noninvasive tool for the evaluation of cardiac disorders. There is a dearth of information on the utility of ECG in general practice in Nigeria. We assessed the knowledge and utilization of ECG among family medicine residents in Nigeria. Materials and Methods: A cross‑sectional evaluation was conducted between November 2011 and May 2012 in four family medicine training centers in Nigeria. A self‑administered questionnaire was used to obtain information from the resident doctors regarding their ECG requests, preferred source of interpretation, most common ECG diagnosis, and update of ECG knowledge. Results: Only 61 out of 120 questionnaires (50.8%) were returned. The respondents were mostly between 31 and 40 years (54.7%) and were predominantly males (73.8%) and senior residents (65.6%). Fifty‑four (88.3%) respondents made

Classical Kaposi’s sarcoma (KS) typically affects elderly men of Mediterranean and Jewish origin. We present an unusual case of classical KS in a human immunodeficiency virus (HIV) negative elderly farmer from rural Nigeria. He had multiple brownish nodules and plaques on both lower extremities associated with lymphoedema. Histopathological examination of a biopsy of the skin nodule confirmed the diagnosis of KS. The lesions only showed marginal improvement on chemotherapy which necessitated a referral for radiotherapy. There is a need to look beyond the traditional geographical distinction of KS variants as we continue to experience a dynamic role for environmental co-factors in the development of KS.

Introduction: Human immunodeficiency virus (HIV) negatively impacts the natural history of hepatitis B virus (HBV) infection, including replication. We determined the prevalence of HBeAg in HIV/HBV co-infected patients compared to HBV mono-infected controls and further investigated the relationship between HBeAg seropositivity and the degree of HIV-induced immunosuppression in co-infected patients. Methodology: The study design was cross-sectional. One hundred HBsAg-positive HIV-infected adults and 100 age and sex matched HBsAg-positive HIV negative controls were consecutively recruited between May and November 2010. Relevant demographic and HBV-related information was obtained. HBeAg was assayed by semi-quantitative third generation ELISA. The HIV/HBV co-infected patients also had CD4+ cell and HIV viral load quantification measured using flow cytometry and polymerase chain reaction techniques respectively. Results: In each group, the mean age was 34 ± 8 years and the majority (61%) was female. The prevalence of HBeAg was significantly higher among co-infected patients (n = 28; 28%) than in the controls (n = 15; 15%; p = 0.03). HBeAg seropositivity was independently associated with age < 40 years (AOR = 2.83, 95% = CI 1.29-6.17) and HIV seropositivity (AOR = 2.44, 95% C.I = 1.17-5.07). The prevalence of HBeAg was significantly higher in co-infected patients with CD4 cell count < 200 cell/µL (41.3%) compared to those with 200-499 cell/µL (18.6%) and ≥500 cell/µL (9.1%), p = 0.006. Conclusion: HIV/HBV co-infected patients have a significantly higher prevalence of HBeAg than HBV mono-infected individuals. HBV-infected patients should be routinely assessed for HBeAg, especially if they are co-infected with HIV.

BACKGROUND We investigated predictors of in-hospital mortality and length of hospital stay among adults with community-acquired pneumonia (CAP) in Nigeria in order to provide recommendations to improve CAP outcomes in developing countries. METHODS This was a multi-centre case control study of patients ≥18 years who were admitted with CAP between 2008 and 2012. Case notes of 100 consecutive patients who died (cases) and random sample of 300 patients discharged (controls) were selected. RESULTS Mean ages were 55.4±19.6 (cases) and 49.3±19.2 (controls). Independent predictors of mortality were CURB-65 score ≥3: adjusted odds ratio (aOR) 24.3, late presentation: aOR 8.6, co-morbidity: aOR 3.9, delayed first dose antibiotics (>4 hours): aOR 3.5, need for supplemental oxygen: aOR 4.9, multilobar pneumonia: aOR 4.0, non-pneumococcal aetiology: aOR 6.5, anaemia: aOR 3.8 and hyperglycemia: aOR 8.6. CURB-65 ≥3 predicted mortality with a high specificity (96.1%) but low sensitivity (75%); positive predictive value of 88.2% and negative predictive value of 90.8%. Care in hospital A and B: aOR 3.3 and 2.2 respectively, male gender aOR 2.1, co-morbidity aOR 3.0, anaemia aOR 2.1 and elevated serum creatinine aOR 6.3 independently predicted length of hospital stay >10 days among survivors. CONCLUSIONS Several modifiable patient-related and process-of-care factors predicted in-hospital mortality, and length of hospital stay among survivors. Our findings should be used to improve CAP outcomes in developing countries.

Background In Nigeria, where malaria is endemic, greater than 70% of febrile illnesses are treated presumptively as malaria, often without a laboratory evaluation for other possible causes of fever. This cross-sectional study evaluated the presence of dengue virus infection in febrile patients, presumptively diagnosed of malaria infections in the clinic. Methodology Blood samples were collected from 529 febrile patients (246 in Jos and 283 in Maiduguri) attending the general outpatient clinics of the Jos University Teaching Hospital (JUTH) and the University of Maiduguri Teaching Hospital (UMTH) and tested for anti-dengue immunoglobulin M (IgM) and immunoglobulin G (IgG), as well as anti-non-structural protein (NS1) by ELISA. The samples were also evaluated for presence of P. falciparum malaria parasites by microscopic examination of Giemsa-stained blood smears. Results The prevalence of confirmed, highly suggestive and probable dengue virus infections categorized in relation to duration of illness since onset of fever were 2.3%, 5.5% and 1.5% respectively, while the prevalence of anti-flavivirus IgG and IgM seropositivity was 11.7%. In a total of 117 (22.1%) patients (32 in Jos, 85 in Maiduguri), malaria parasites were detected by blood smear microscopy, out of which 7 (6%) also had a positively confirmed, highly suggestive or probable dengue test result. Conclusion Although the high cross-reactivity of anti-flavivirus antibodies should be taken into account in the interpretation of the seroprevalence data, our findings suggest a significant presence of dengue virus in this environment, some of which may otherwise be misdiagnosed as malaria. These findings are strong enough to recommend serological screening for anti-dengue virus titer and NS1 antigen for all febrile patients, as part of fever diagnostic protocols in tropical regions. Given the prevalence of dengue virus infections, there is also a need for a dengue control program and public education to prevent outbreaks and occurrence of severe dengue complications.

Objective To describe our experiences in the management of a case of Lassa fever (LF) and follow-up of nosocomial primary contacts during the 2014 Ebola outbreak in West Africa. Methods Clinical management of the index case and infection control/surveillance activities for primary contacts are described. Laboratory confirmation was by Lassa virus-specific reverse-transcriptase PCR. Results A 28-year-old man with a 10-day history of febrile illness was referred to a major tertiary hospital in south-east Nigeria from a city that previously experienced a LF outbreak and was recently affected by Ebola. On observation of haemorrhagic features, clinicians were at a crossroads. Diagnosis of LF was confirmed at a National Reference Centre. The patient died despite initiation of ribavirin therapy. Response activities identified 121 primary contacts comprising 78 (64.5%) hospital staff/interns, 19 (15.7%) medical students, 18 (14.9%) inpatients and 6 (5.0%) relatives. Their mean age was 32.8 ± 6.6 years, and 65.3% were women. Twenty (16.5%) had high-risk exposure and were offered ribavirin as post-exposure prophylaxis. No secondary case of LF occurred. Fatigue (43.8%) and dizziness (31.3%) were the commonest side effects of ribavirin. Conclusions Response activities contained nosocomial spread of LF, but challenges were experienced including lack of a purpose-built isolation facility, absence of local Lassa virus laboratory capacity, failure to use appropriate protective equipment and stigmatisation of contacts. A key lesson is that the weak health systems of Africa should be comprehensively strengthened; otherwise, we might win the Ebola battle but lose the one against less virulent infections for which effective treatment exists. Objectif Decrire nos experiences dans la prise en charge d'un cas de fievre de Lassa (FL) et le suivi des contacts primaires d'infections nosocomiales lors de l’epidemie d'Ebola en 2014 en Afrique de l'Ouest. Methodes La prise en charge clinique du cas index et les activites de lutte/surveillance de l'infection pour les contacts primaires sont decrites. La confirmation de laboratoire a ete obtenue par la PCR basee sur la transcriptase inverse specifique du virus Lassa. Resultats Un homme de 28 ans avec une histoire de maladie febrile de 10 jours a ete refere dans un hopital tertiaire majeur dans le sud-est du Nigeria, dans une ville qui a precedemment connu une epidemie de FL et avait recemment ete affectee par le virus Ebola. Suivant l'observation des caracteristiques hemorragiques, les cliniciens sont arrives a differentes voies possibles. Le diagnostic de la FL a ete confirme dans un centre national de reference. Le patient est decede malgre l'instauration du traitement au ribavirine. Les activites de reponse ont identifie 121 contacts primaires comprenant 78 (64,5%) membres/stagiaires du personnel de l'hopital, 19 (15,7%) etudiants en medecine, 18 (14,9%) patients hospitalises et 6 (5,0%) parents. Leur âge moyen etait de 32,8 ± 6,6 ans et 65,3% etaient des femmes. Vingt (16,5%) avaient subi une forte exposition au risque et ont recu du ribavirine comme prophylaxie post-exposition. Aucun cas secondaire de FL n'est survenu. La fatigue (43,8%) et des malaises (31,3%) etaient les effets secondaires les plus courants du ribavirine. Conclusions Les activites d'intervention ont contenu la propagation nosocomiale de la FL mais des defis ont ete rencontres notamment l'absence d'un espace d'isolement construit a cet effet, l'absence de capacites locales de laboratoire pour le virus de Lassa, le defaut d'utilisation de l’equipement approprie de protection et la stigmatisation des contacts. Une lecon a retenir est la faiblesse des systemes de sante en Afrique qui devraient etre renforces globalement, sinon nous pourrions gagner la bataille contre Ebola mais perdre celle contre des infections moins virulentes pour lesquelles un traitement efficace existe. Objetivo Describir nuestras experiencias en el manejo de un caso de Fiebre de Lassa (FL) y el seguimiento de los contactos nosocomiales primarios durante el brote del virus de Ebola del 2014 en Africa Occidental. Metodos Se describe el manejo clinico del caso indexado y las actividades de control/vigilancia de la infeccion entre los contactos primarios. La confirmacion en el laboratorio se realizo mediante una PCR transcriptasa inversa especifica para el VL. Resultados Un hombre de 28 anos con una historia de 10 dias de fiebre fue referido a un hospital terciario del sudeste de Nigeria desde una ciudad en la que previamente se habia declarado un brote de FL y que recientemente habia sido afectada por el Ebola. Al observar caracteristicas hemorragicas, los clinicos se encontraron en una encrucijada. El diagnostico de FL se confirmo en el Centro de Referencia Nacional. El paciente murio a pesar de iniciar tratamiento con Ribavirin. Las actividades de respuesta identificaron 121 contactos primarios que incluian 78 (64.5%) sanitarios / internos hospitalarios, 19 (15.7%) estudiantes de medicina, 18 (14.9%) pacientes ingresados y 6 (5.0%) familiares. La edad media era de 32.8 ± 6.6 anos y un 65.3% eran mujeres. Veinte (16.5%) tenian un alto riesgo de exposicion y se les ofrecio una profilaxis post-exposicion con Ribavirin. No hubo un caso secundario de FL. Fatiga (43.8%) y mareos (31.3%) fueron los principales efectos secundarios de Ribavirin. Conclusiones Las actividades de respuesta consiguieron contener la propagacion del VL pero se experimentaron retos incluyendo la falta de una instalacion de aislamiento especificamente disenada y construida, falta de capacidad de laboratorio local para la deteccion del VL, falta de uso de equipos de proteccion apropiados y estigmatizacion de los contactos. Una leccion clave es que los debiles sistemas de salud del Africa deberian fortalecerse de forma integral, o de lo contrario puede que se gane la batalle contra el Ebola pero se pierdan otras contra infecciones menos virulentas para las cuales existen tratamientos efectivos.

A clear knowledge of the pathogens responsible for community-acquired pneumonia (CAP) in a given region and their antibiotic sensitivity patterns is necessary for optimal treatment. We determined the common bacterial pathogens causing CAP in Nigeria and further reviewed their antibiotic senstivity patterns with a view to providing recommendations to improve antibiotic management of CAP.Case notes of all adult patients who were 18 years or more admitted to four major tertiary hospitals in South East Nigeria with a diagnosis of CAP between 2008 and 2012 were retrospectively studied. To be eligible, patients were required to have sputum culture and sensitivity results available. Socio-demographic, clinical, pre-admission and in-hospital treatment data were also obtained.Of 400 patients with a radiologically confirmed diagnosis of CAP, 232 fulfilled the study criteria; 122 (52.6%) were women and the mean age was 50.6 ± 18.8 years. Aetiological agents were identified from sputum in 189 (81.5%) patients. Streptococcus pneumoniae (n = 90, 47.6%) was the most frequent isolate followed by Klebsiella pneumoniae (n = 62, 32.8%), Staphylococcus aureus (n = 24, 12.7%) and Streptococcus pyogenes (n = 13, 6.9%). The pathogens were most sensitive to levofloxacin (77%), ceftazidime (75.5%) and ofloxacin (55.8%). The susceptibility of the isolates to antibiotics most frequently presecribed for empirical therapy was low (co-amoxiclav, 47.6%; ciprofloxacin, 45.9% and ceftriaxone, 47.6%) and this was associated with higher mortality and/or longer duration of hospital stay in survivors.Strep. pneumoniae and K. pneumoniae were the most common causes of CAP. The pathogens were most sensitive to levofloxacin and ceftazidime. We suggest that these antibiotics should increasingly be considered as superior options for empirical treatment of CAP in Nigeria.

Summary Data on baseline hepatic function of HIV and hepatitis B virus (HBV) co-infected patients are limited in sub-Saharan Africa. We assessed liver function test (LFT) abnormalities in Nigerian patients with HIV/HBV co-infection to highlight the impact of HIV on HBV-related liver disease in sub-Saharan Africa. A cross-sectional study involving 100 HIV/HBV co-infected patients and 100 age- and sex-matched HBV mono-infected controls. Blood testing for HIV antibodies, CD4+ cell count, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), LFTs, platelet count, fasting blood glucose and lipid profile were carried out. Non-invasive hepatic fibrosis scores (aspartate aminotransferase-platelet ratio index [APRI] and FIB-4) were also calculated. Co-infected patients had deranged liver enzymes more than the controls (77% versus 64%, P = 0.04). The predominant patterns of enzyme derangement in co-infected patients were either predominantly ↑ALP (30% versus 4%, P < 0.0001) or mixed (30% versus 15%, P = 0.01) but predominantly ↑AST/ALT in the controls (25% versus 9%, P = 0.003). Co-infected patients had higher fibrosis scores for both APRI ( P = 0.002) and FIB-4 ( P = 0.0001). On further analysis, LFT abnormalities and fibrosis scores were only significantly higher in co-infected patients in the immune clearance and HBeAg-negative chronic hepatitis phases. LFT abnormalities are common in Nigerians with HBV infection and co-infection with HIV negatively impacts on hepatic function.

BACKGROUND Second-line antiretroviral therapy (ART) accounts for less than 5% of total ART in resource-limited settings. We described the baseline characteristics, reasons for switch and treatment outcomes of Nigerian patients receiving second-line ART. METHODS In this retrospective cohort study we recorded the baseline characteristics of HIV-infected adults whose treatment regimen was switched from a non-nucleoside reverse transcriptase inhibitor, a first-line agent, to a protease inhibitor-based second-line regimen. The duration of follow-up was 12 months. RESULTS Of 4229 patients who started first-line therapy, 186 (4.4%) were switched to second-line therapy after a mean duration of 16.6 ± 7.6 months. Their mean age was 41.8 ± 9.6 years and 59.1% were women. The median (range) viral load and CD4 cell counts at switch were 4.7 (4.1-6.3) log10 copies/ml and 71 (6-610) cells/µl, respectively. The predominant reason for switch was virological failure (79.0%). Only 55.4% and 36.6% of patients had CD4 cell count and viral load at 12 months. About 82%, 79% and 82% of patients with available data achieved virological suppression at 3 months, 6 months and 12 months respectively (p = 0.81). The proportion of patients who achieved ≥50% rise in CD4 cell count increased from 55.8% at 3 months to 78.6% at 12 months (p = 0.0002). CONCLUSION The rate of switch to second-line therapy was low but there were good treatment outcomes among patients with available data. Attrition rate was high. Regular viral load monitoring, improved availability/affordability of second-line regimens and retention in care should become priorities in resource-limited settings.

Despite the growing body of evidence on the interaction between HIV and malaria in sub-Saharan Africa, there is a dearth of data on clinical malaria in HIV-infected patients in Nigeria. We determined the burden of clinical malaria in HIVinfected adult Nigerians and further investigated the association between their immunological status and the rates of clinical malaria. Ninety seven antiretroviral treatment-naïve HIV-infected adults were enrolled in a cross-sectional study from August to December, 2009. The participants had a complete clinical evaluation, thick and thin blood films for malaria parasites and CD4 cell count quantification. Clinical malaria was defined as having fever (temperature ≥ 37.5oC or history of fever within 48 hours) and a malaria parasite density above the median value obtained for subjects with co-existing fever and parasitaemia. Clinical malaria was diagnosed in 10 out of 97 patients (10.3%). Lower CD4 cell counts were associated with increasing rates of clinical malaria which was 0% at CD4 cell count of ≥ 500, 2.6% at 200-499 and 30% at

The aim of the present study was to evaluate the determinants of HIV-related cardiac disease (HRCD) among adults in north central Nigeria. This was a hospital-based cross-sectional study recruiting patients who were HIV positive attending the HIV clinic at Jos University teaching Hospital, Nigeria.A total of 200 adults who were HIV positive and aged ≥18 years were consecutively recruited. All patients were administered a questionnaire and underwent clinical examination, laboratory investigation for haemoglobin estimation, CD4 cell count, viral load, serum lipid profile, hepatitis B surface antigen, anti-hepatitis C virus antibody, electrocardiogram and two-dimensional echocardiography Doppler studies. The outcome measure was echocardiography-defined cardiac disease, such as systolic dysfunction, diastolic dysfunction, isolated left ventricular dilatation, right ventricular dysfunction or pulmonary hypertension.The mean age of the study population was 38±9 years. The majority (71%) were women and were on average younger than the men (36±8 years vs 47±9 years, p0.0002). Highly active anti-retroviral therapy (HAART) use was seen in 84.4% of subjects. The median CD4 cell count for the study population was 358 cells/µL; the count was 459 (95% CI 321 to 550) cells/µL for subjects without HRCD and 193 (95% CI 126 to 357) cells/µL for subjects with HRCD (p0.001). HAART-naive subjects with HRCD had a mean CD4 cell count of 121 cells/µL vs 200 cells/µL for those on HAART (p0.01). CD4 cell count (OR = 0.25, 95% CI 0.15 to 0.45) and duration of diagnosis (OR=3.88, 95% CI 1.20 to 13.71) were the significant determinants of HRCD on multivariate analysis.Duration of HIV diagnosis and degree of immunosuppression were the significant determinants of HRCD. There is therefore a need to reduce cardiovascular morbidity in patients infected with HIV through early diagnosis/sustained use of HAART, early screening for HRCD and prompt intervention.

Background: The introduction of Highly Active Antiretroviral Therapy (HAART) has led to decline in HIV-related opportunistic infections in high-income settings. We determined the prevalence and risk factors for opportunistic infections among patients receiving HAART in a resource-limited setting in Nigeria. Methodology: A descriptive and analytical cross-sectional study among adult HIV-infected patients receiving HAART for a median duration of 3 years at the Federal Medical Centre, Owerri, Nigeria was conducted. Data on pre- HAART socio-demographic, clinical and laboratory characteristics were obtained. Post-HAART data were collected through history, physical examination and laboratory investigations. Result: The mean age of the participants was 41.1 ± 10.0 years; and females were in the majority (65.8%). Half (50.4%) belonged to the lower socio-economic class. At baseline (pre-HAART), 72.3% of the participants belonged to World Health Organization (WHO) clinical stage 1 or 2. The median pre-HAART CD4 cell count of the patients was 200 (110-263) cells/μl while the median post-HAART CD4 cell count was 357 (211-496) cells/μl. The majority (77.6%) were adherent on HAART. Out of 339 patients, 76 (22.4%) had opportunistic infections. The leading conditions were candidiasis (8.6%), tuberculosis (7.7%), dermatitis (5.6%), chronic diarrhea (1.5%) and sepsis (1.5%). The independent risk factors for opportunistic infections were household income < 20,000 (Adjusted odds ratio [AOR] = 2.70, 95% CI 1.18-6.18), advanced baseline WHO clinical stage (AOR=9.49, 95% CI 4.20-21.42), baseline hemoglobin