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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.

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.

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.

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