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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.

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.

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.

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.

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.

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.

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.

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.

Introduction The COVID-19 pandemic continues to overwhelm health systems across the globe. We aimed to assess the readiness of hospitals in Nigeria to respond to the COVID-19 outbreak. Method Between April and October 2020, hospital representatives completed a modified World Health Organisation (WHO) COVID-19 hospital readiness checklist consisting of 13 components and 124 indicators. Readiness scores were classified as adequate (score ≥80%), moderate (score 50–79.9%) and not ready (score Results Among 20 (17 tertiary and three secondary) hospitals from all six geopolitical zones of Nigeria, readiness score ranged from 28.2% to 88.7% (median 68.4%), and only three (15%) hospitals had adequate readiness. There was a median of 15 isolation beds, four ICU beds and four ventilators per hospital, but over 45% of hospitals established isolation facilities and procured ventilators after the onset of COVID-19. Of the 13 readiness components, the lowest readiness scores were reported for surge capacity (61.1%), human resources (59.1%), staff welfare (50%) and availability of critical items (47.7%). Conclusion Most hospitals in Nigeria were not adequately prepared to respond to the COVID-19 outbreak. Current efforts to strengthen hospital preparedness should prioritize challenges related to surge capacity, critical care for COVID-19 patients, and staff welfare and protection.

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 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.

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 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 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 3, IQR:130–547 vs. 277cells/mm3, 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 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.

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.

Recent outbreaks of viral hemorrhagic fevers (VHFs), including Ebola virus disease (EVD) and Lassa fever (LF), highlight the urgent need for sensitive, deployable tests to diagnose these devastating human diseases. 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. We perform safety testing to demonstrate the efficacy of our HUDSON protocol in heat-inactivating VHF viruses before SHERLOCK testing, eliminating the need for an extraction. We develop a user-friendly protocol and mobile application (HandLens) to report results, facilitating SHERLOCK’s use in endemic regions. Finally, we successfully deploy our tests in Sierra Leone and Nigeria in response to recent outbreaks., Outbreaks of viral hemorrhagic fevers highlight the need for sensitive, field-deployable diagnostics. Here the authors present a CRISPR-based SHERLOCK platform with field protocol and mobile app for Ebola and Lassa fever outbreaks.

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.

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)

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.