Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico.

BACKGROUND: NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America. METHODS: We conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (≥18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed. RESULTS: Of the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted - 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest - largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose. CONCLUSIONS: NVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains. (Funded by Novavax and others; PREVENT-19 ClinicalTrials.gov number, NCT04611802.).

Safety and Immunogenicity of Accelerated Heterologous Two-dose Ebola Vaccine Regimens in Adults With and Without HIV in Africa.

BACKGROUND: Shorter prophylactic vaccine schedules may offer more rapid protection against Ebola in resource-limited settings. METHODS: This randomized, observer-blind, placebo-controlled, phase 2 trial conducted in five sub-Saharan African countries included people without HIV (PWOH, n = 249) and people living with HIV (PLWH, n = 250). Adult participants received one of two accelerated Ebola vaccine regimens (MVA-BN-Filo, Ad26.ZEBOV administered 14 days apart [n = 79] or Ad26.ZEBOV, MVA-BN-Filo administered 28 days apart [n = 322]) or saline/placebo (n = 98). The primary endpoints were safety (adverse events [AEs]) and immunogenicity (Ebola virus [EBOV] glycoprotein-specific binding antibody responses). Binding antibody responders were defined as participants with a > 2.5-fold increase from baseline or the lower limit of quantification if negative at baseline. RESULTS: The mean age was 33.4 years, 52% of participants were female, and among PLWH, the median (interquartile range) CD4+ cell count was 560.0 (418.0-752.0) cells/µL. AEs were generally mild/moderate with no vaccine-related serious AEs or remarkable safety profile differences by HIV status. At 21 days post-dose 2, EBOV glycoprotein-specific binding antibody response rates in vaccine recipients were 99% for the 14-day regimen (geometric mean concentrations [GMCs]: 5168 enzyme-linked immunosorbent assay units (EU)/mL in PWOH; 2509 EU/mL in PLWH), and 98% for the 28-day regimen (GMCs: 6037 EU/mL in PWOH; 2939 EU/mL in PLWH). At 12 months post-dose 2, GMCs in PWOH and PLWH were 635 and 514 EU/mL, respectively, for the 14-day regimen and 331 and 360 EU/mL, respectively, for the 28-day regimen. CONCLUSIONS: Accelerated 14- and 28-day Ebola vaccine regimens were safe and immunogenic in PWOH and PLWH in Africa. TRIAL REGISTRATION: NCT02598388.

Safety, tolerability, and immunogenicity of the chimpanzee adenovirus type 3-vectored Marburg virus (cAd3-Marburg) vaccine in healthy adults in the USA: a first-in-human, phase 1, open-label, dose-escalation trial.

BACKGROUND: WHO has identified Marburg virus as an emerging virus requiring urgent vaccine research and development, particularly due to its recent emergence in Ghana. We report results from a first-in-human clinical trial evaluating a replication-deficient recombinant chimpanzee adenovirus type 3 (cAd3)-vectored vaccine encoding a wild-type Marburg virus Angola glycoprotein (cAd3-Marburg) in healthy adults. METHODS: We did a first-in-human, phase 1, open-label, dose-escalation trial of the cAd3-Marburg vaccine at the Walter Reed Army Institute of Research Clinical Trials Center in the USA. Healthy adults aged 18-50 years were assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1 × 1010 or 1 × 1011 particle units (pu). Primary safety endpoints included reactogenicity assessed for the first 7 days and all adverse events assessed for 28 days after vaccination. Secondary immunogenicity endpoints were assessment of binding antibody responses and T-cell responses against the Marburg virus glycoprotein insert, and assessment of neutralising antibody responses against the cAd3 vector 4 weeks after vaccination. This study is registered with ClinicalTrials.gov, NCT03475056. FINDINGS: Between Oct 9, 2018, and Jan 31, 2019, 40 healthy adults were enrolled and assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1 × 1010 pu (n=20) or 1 × 1011 pu (n=20). The cAd3-Marburg vaccine was safe, well tolerated, and immunogenic. All enrolled participants received cAd3-Marburg vaccine, with 37 (93%) participants completing follow-up visits; two (5%) participants moved from the area and one (3%) was lost to follow-up. No serious adverse events related to vaccination occurred. Mild to moderate reactogenicity was observed after vaccination, with symptoms of injection site pain and tenderness (27 [68%] of 40 participants), malaise (18 [45%] of 40 participants), headache (17 [43%] of 40 participants), and myalgia (14 [35%] of 40 participants) most commonly reported. Glycoprotein-specific antibodies were induced in 38 (95%) of 40 participants 4 weeks after vaccination, with geometric mean titres of 421 [95% CI 209-846] in the 1 × 1010 pu group and 545 [276-1078] in the 1 × 1011 pu group, and remained significantly elevated at 48 weeks compared with baseline titres (39 [95% CI 13-119] in the 1 ×1010 pu group and 27 [95-156] in the 1 ×1011 pu group; both p<0·0001). T-cell responses to the glycoprotein insert and neutralising responses against the cAd3 vector were also increased at 4 weeks after vaccination. INTERPRETATION: This first-in-human trial of this cAd3-Marburg vaccine showed the agent is safe and immunogenic, with a safety profile similar to previously tested cAd3-vectored filovirus vaccines. 95% of participants produced a glycoprotein-specific antibody response at 4 weeks after a single vaccination, which remained in 70% of participants at 48 weeks. These findings represent a crucial step in the development of a vaccine for emergency deployment against a re-emerging pathogen that has recently expanded its reach to new regions. FUNDING: National Institutes of Health.

Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies.

Understanding the dynamics of early immune responses to HIV-1 infection, including the evolution of initial neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, will inform HIV vaccine design. In this study, we assess the development of autologous neutralizing antibodies (ANAbs) against founder envelopes (Envs) from 18 participants with HIV-1 CRF01_AE acute infection. The timing of ANAb development directly associated with the magnitude of the longitudinal ANAb response. Participants that developed ANAbs within 6 months of infection had significantly higher ANAb responses at 1 year (50% inhibitory concentration [IC50] geometric mean titer [GMT] = 2,010 versus 184; P = 0.001) and 2 years (GMT = 3,479 versus 340; P = 0.015), compared to participants that developed ANAb responses after 6 months. Participants with later development of ANAb tended to develop an earlier, potent heterologous tier 1 (92TH023) neutralizing antibody (NAb) response (P = 0.049). CRF01_AE founder Env V1V2 loop lengths correlated indirectly with the timing (P = 0.002, r = -0.675) and directly with magnitude (P = 0.005, r = 0.635) of ANAb responses; Envs with longer V1V2 loop lengths elicited earlier and more potent ANAb responses. While ANAb responses did not associate with viral load, the viral load set point correlated directly with neutralization of the heterologous 92TH023 strain (P = 0.007, r = 0.638). In contrast, a striking inverse correlation was observed between viral load set point and peak ADCC against heterologous 92TH023 Env strain (P = 0.0005, r = -0.738). These data indicate that specific antibody functions can be differentially related to viral load set point and may affect HIV-1 pathogenesis. Exploiting Env properties, such as V1V2 length, could facilitate development of subtype-specific vaccines that elicit more effective immune responses and improved protection. IMPORTANCE Development of an effective HIV-1 vaccine will be facilitated by better understanding the dynamics between the founder virus and the early humoral responses. Variations between subtypes may influence the evolution of immune responses and should be considered as we strive to understand these dynamics. In this study, autologous founder envelope neutralization and heterologous functional humoral responses were evaluated after acute infection by HIV-1 CRF01_AE, a subtype that has not been thoroughly characterized. The evolution of these humoral responses was assessed in relation to envelope characteristics, magnitude of elicited immune responses, and viral load. Understanding immune parameters in natural infection will improve our understanding of protective responses and aid in the development of immunogens that elicit protective functional antibodies. Advancing our knowledge of correlates of positive clinical outcomes should lead to the design of more efficacious vaccines.

HIV-1 infections with multiple founders associate with the development of neutralization breadth.

Eliciting broadly neutralizing antibodies (bnAbs) is a cornerstone of HIV-1 vaccine strategies. Comparing HIV-1 envelope (env) sequences from the first weeks of infection to the breadth of antibody responses observed several years after infection can help define viral features critical to vaccine design. We investigated the relationship between HIV-1 env genetics and the development of neutralization breadth in 70 individuals enrolled in a prospective acute HIV-1 cohort. Half of the individuals who developed bnAbs were infected with multiple HIV-1 founder variants, whereas all individuals with limited neutralization breadth had been infected with single HIV-1 founders. Accordingly, at HIV-1 diagnosis, env diversity was significantly higher in participants who later developed bnAbs compared to those with limited breadth (p = 0.012). This association between founder multiplicity and the subsequent development of neutralization breadth was also observed in 56 placebo recipients in the RV144 vaccine efficacy trial. In addition, we found no evidence that neutralization breath was heritable when analyzing env sequences from the 126 participants. These results demonstrate that the presence of slightly different HIV-1 variants in acute infection could promote the induction of bnAbs, suggesting a novel vaccine strategy, whereby an initial immunization with a cocktail of minimally distant antigens would be able to initiate bnAb development towards breadth.

Prevalence of Urogenital Mycoplasma genitalium Infection at 2 US Army Medical Facilities.

BACKGROUND: Sexually transmitted infections (STIs) have a high incidence in the US Armed Forces and can adversely impact service members' ability to perform their duties. Better knowledge of Mycoplasma genitalium (MG) epidemiology in the military is needed to understand the potential impact of this emerging pathogen on force readiness. METHODS: We conducted cross-sectional analyses of data from US Army service members and other Military Health System beneficiaries participating in a trial of an STI/HIV behavioral intervention at Fort Liberty, NC, and Joint Base Lewis-McChord, WA. At enrollment, participants completed questionnaires and provided biological specimens for nucleic acid amplification testing for MG, Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG). We used principal component analysis and robust Poisson regression to examine associations between participant characteristics and prevalent urogenital MG. RESULTS: Among 432 participants enrolled between November 2020 and February 2023, 43 had MG (prevalence, 10.0%), of whom 13 had coinfection with another bacterial STI (all 13 were positive for CT, with 1 also positive for NG). The prevalence of MG was significantly higher among female (13.5%) versus male (7.6%; P = 0.048) participants and non-Hispanic Black (14.9%) versus non-Hispanic White participants (6.6%; P = 0.045). Single relationship status and increased number of recent sexual partners were correlated, and their component was associated with higher MG prevalence (adjusted prevalence ratio, 2.11; 95% confidence interval, 1.29-3.48). CONCLUSIONS: The high prevalence of urogenital MG among Military Health System beneficiaries highlights the importance of understanding the potential clinical sequelae of MG and conducting additional epidemiologic research in military settings.

Impact of weight gain with dolutegravir on antiretroviral adherence and viral suppression in four African countries.

OBJECTIVE: We hypothesized that total body weight (TBW) gain after switching antiretroviral therapy (ART) regimen to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) may negatively impact ART adherence and viral load (VL) and therefore sought to examine these associations. METHODS: The ongoing African Cohort Study (AFRICOS) enrols people with HIV at 12 facilities in Kenya, Nigeria, Tanzania and Uganda supported by The US President's Emergency Plan for AIDS Relief. Among ART-experienced participants who switched to TLD, we used multivariable multinomial logistic regression to examine associations between pre-/post-TLD changes in percentage TBW (≥5% gain, <5% change, ≥5% loss) and changes in self-reported ART adherence (0, 1-2, ≥3 days missed doses in past 30 days) and VL [(<50 copies/mL (undetectable), 50-999 copies/mL (detectable, but suppressed), ≥1000 copies/mL (unsuppressed)]. RESULTS: Among 1508 participants, median time from starting TLD to follow-up was 9 months (interquartile range: 7-11). Overall, 438 (29.1%) participants experienced a TBW gain ≥5%, which was more common among females than among males (32.2% vs 25.2%, p = 0.005) and participants switching from efavirenz [32.0% vs nevirapine (19.9%) and boosted protease inhibitor (20.0%); p < 0.001]. Compared with a TBW change <5% [950 (63.0%) participants], TBW gain ≥5% was not significantly associated with more days with missed ART doses [adjusted odds ratio (aOR) = 0.77, 95% confidence interval (CI): 0.48-1.23] or VL becoming detectable and/or unsuppressed (aOR = 0.69, 95% CI: 0.41-1.16). CONCLUSIONS: Although a substantial proportion of participants experienced weight gain after switching to TLD, we did not identify a significant impact on adherence or virological outcomes.

Perinatal Depressive Symptoms and Viral Non-suppression Among a Prospective Cohort of Pregnant Women Living with HIV in Nigeria, Kenya, Uganda, and Tanzania.

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.

Transitioning women to first-line preferred TLD regimen is lagging in Sub-Saharan Africa.

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 < 0.001) were taking TLD. Kaplan-Meier analysis showed time to transition varied by site, with women in Tanzania transitioning at the same rate as men. In Nigeria, women initially had a slower transition but caught up to men. After adjusting for local policies, women[1] in Kisumu West transitioned at the same rate as men. In South Rift Valley and Uganda, women were less likely to be transitioned. 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.

Predictors of All-Cause Mortality Among People With Human Immunodeficiency Virus (HIV) in a Prospective Cohort Study in East Africa and Nigeria.

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 < 18.5 kg/m2 (aHR 2.20 [95% CI: 1.44-3.38]), clinical depression (aHR 2.42 [95% CI: 1.40-4.18]), World Health Organization (WHO) stage III (aHR 2.18 [95% CI: 1.31-3.61]), a g/dL increase in hemoglobin (aHR 0.79 [95% CI: .72-.85]), and every year on ART (aHR 0.67 [95% CI: .56-.81]). 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.

Coronavirus Antibody Responses before COVID-19 Pandemic, Africa and Thailand.

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 (p<0.0001). 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 (p<0.01). We noted less pronounced differences for endemic coronaviruses. Serosurveys could affect vaccine and monoclonal antibody distribution across global populations.

Individual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV Infection.

OBJECTIVE: We examined individual differences in CD4/CD8 T-cell ratio trajectories and associated risk profiles from acute HIV infection (AHI) through 144 weeks of antiretroviral therapy (ART) using a data-driven approach. METHODS: A total of 483 AHI participants began ART during Fiebig I-V and completed follow-up evaluations for 144 weeks. CD4+, CD8+, and CD4/CD8 T-cell ratio trajectories were defined followed by analyses to identify associated risk variables. RESULTS: Participants had a median viral load (VL) of 5.88 copies/ml and CD4/CD8 T-cell ratio of 0.71 at enrollment. After 144 weeks of ART, the median CD4/CD8 T-cell ratio was 1.3. Longitudinal models revealed five CD4/CD8 T-cell ratio subgroups: group 1 (3%) exhibited a ratio >1.0 at all visits; groups 2 (18%) and 3 (29%) exhibited inversion at enrollment, with normalization 4 and 12 weeks after ART, respectively; and groups 4 (31%) and 5 (18%) experienced CD4/CD8 T-cell ratio inversion due to slow CD4+ T-cell recovery (group 4) or high CD8+ T-cell count (group 5). Persistent inversion corresponded to ART onset after Fiebig II, higher VL, soluble CD27 and TIM-3, and lower eosinophil count. Individuals with slow CD4+ T-cell recovery exhibited higher VL, lower white blood cell count, lower basophil percent, and treatment with standard ART, as well as worse mental health and cognition, compared with individuals with high CD8+ T-cell count. CONCLUSIONS: Early HIV disease dynamics predict unfavorable CD4/CD8 T-cell ratio outcomes after ART. CD4+ and CD8+ T-cell trajectories contribute to inversion risk and correspond to specific viral, immune, and psychological profiles during AHI. Adjunctive strategies to achieve immune normalization merit consideration.

PEPFAR's Role in Protecting and Leveraging HIV Services in the COVID-19 Response in Africa.

PURPOSE OF REVIEW: We describe the impact of COVID-19 on PEPFAR programs in Africa and how PEPFAR adapted and leveraged its interventions to the changing landscape of the COVID-19 pandemic. RECENT FINDINGS: To mitigate the potential impact of COVID-19 on the HIV response and protect the gains, continuity of treatment was the guiding principle regarding the provision of services in PEPFAR-supported countries. As the COVID-19 pandemic matured, PEPFAR's approach evolved from a strictly "protect and salvage" approach to a "restore and accelerate" approach that embraced innovative adaptations in service and "person-centered" care. The impact of service delivery interruptions caused by COVID-19 on progress towards HIV epidemic control in PEPFAR-supported African countries remains undetermined. With COVID vaccine coverage many months away and more transmissible variants being reported, Africa may experience more pandemic surges. HIV programs will depend on nimble and innovative adaptations in prevention and treatment services in order to advance epidemic control objectives.

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

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.

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

OBJECTIVE: We determined the prevalence and identified predictors of food insecurity in four African countries. DESIGN: Cross-sectional analyses at study enrolment. SETTING: From January 2013 to March 2020, people living with HIV (PLWH) and without HIV were enrolled at twelve clinics in Kenya, Uganda, Tanzania and Nigeria. PARTICIPANTS: Participants reporting not having enough food to eat over the past 12 months or receiving <3 meals/d were defined as food insecure. Robust Poisson regression models were used to estimate unadjusted and adjusted prevalence ratios (aPR) and 95 % CI for predictors of food insecurity among all participants and separately among PLWH. RESULTS: 1694/3496 participants (48·5 %) reported food insecurity at enrolment, with no difference by HIV status. Food insecurity was more common among older participants (50+ v. 18-24 years aPR 1·35, 95 % CI 1·15, 1·59). Having 2-5 (aPR 1·14, 95 % CI 1·01, 1·30) or >5 dependents (aPR 1·17, 95 % CI 1·02, 1·35), and residing in Kisumu West, Kenya (aPR 1·63, 95 % CI 1·42, 1·87) or Nigeria (aPR 1·20, 95 % CI 1·01, 1·41) was associated with food insecurity. Residing in Tanzania (aPR 0·65, 95 % CI 0·53, 0·80) and increasing education (secondary/above education v. none/some primary education aPR 0·73, 95 % CI 0·66, 0·81) was protective against food insecurity. Antiretroviral therapy (ART)-experienced PLWH were more likely to be food secure irrespective of viral load. CONCLUSION: Food insecurity was highly prevalent in our cohort though not significantly associated with HIV. Policies aimed at promoting education, elderly care, ART access in PLWH and financial independence could potentially improve food security in Africa.

Routine HIV clinic visit adherence in the African Cohort Study.

BACKGROUND: Retention in clinical care is important for people living with HIV (PLWH). Evidence suggests that missed clinic visits are associated with interruptions in antiretroviral therapy (ART), lower CD4 counts, virologic failure, and overlooked coinfections. We identified factors associated with missed routine clinic visits in the African Cohort Study (AFRICOS). METHODS: In 2013, AFRICOS began enrolling people with and without HIV in Uganda, Kenya, Tanzania, and Nigeria. At enrollment and every 6 months thereafter, sociodemographic questionnaires are administered and clinical outcomes assessed. Missed clinic visits were measured as the self-reported number of clinic visits missed in the past 6 months and dichotomized into none or one or more visits missed. Logistic regression with generalized estimating equations was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between risk factors and missed visits. RESULTS: Between January 2013 and March 2020, 2937 PLWH were enrolled, of whom 2807 (95.6%) had initiated ART and 2771 had complete data available for analyses. Compared to PLWH 50+, missed clinic visits were more common among those 18-29 years (aOR 2.33, 95% CI 1.65-3.29), 30-39 years (aOR 1.59, 95% CI 1.19-2.13), and 40-49 years (aOR 1.42, 95% CI 1.07-1.89). As compared to PLWH on ART for < 2 years, those on ART for 4+ years were less likely to have missed clinic visits (aOR 0.72, 95% CI 0.55-0.95). Missed clinic visits were associated with alcohol use (aOR 1.34, 95% CI 1.05-1.70), a history of incarceration (aOR 1.42, 95% CI 1.07-1.88), depression (aOR 1.47, 95% CI 1.13-1.91), and viral non-suppression (aOR 2.50, 95% CI 2.00-3.12). As compared to PLWH who did not miss any ART in the past month, missed clinic visits were more common among those who missed 1-2 days (aOR 2.09, 95% CI 1.65-2.64) and 3+ days of ART (aOR 7.06, 95% CI 5.43-9.19). CONCLUSIONS: Inconsistent clinic attendance is associated with worsened HIV-related outcomes. Strategies to improve visit adherence are especially needed for young PLWH and those with depression.

Transient Reductions in Human Immunodeficiency Virus (HIV) Clinic Attendance and Food Security During the Coronavirus Disease 2019 (COVID-19) Pandemic for People Living With HIV in 4 African Countries.

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.

Pretreatment and Acquired Antiretroviral Drug Resistance Among Persons Living With HIV in Four African Countries.

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.

Prevalence and risk factors associated with HIV and syphilis co-infection in the African Cohort Study: a cross-sectional study.

BACKGROUND: Each year, 5.6 million new syphilis cases are diagnosed globally. Guidelines for people living with HIV (PLWH) in low-income countries (LIC) recommend STI testing for symptomatic persons and those newly diagnosed with HIV; routine STI testing is less clear. Here we provide updated syphilis prevalence and identify co-infection risk factors in PLWH in the African Cohort Study (AFRICOS) to understand these rates as they relate to syndromic treatment. METHODS: AFRICOS is a study enrolling PLWH and HIV-uninfected individuals in four African countries. Participant study enrollment information was used to determine syphilis prevalence and co-infection risk factors. Inclusion criteria consisted of adults 18 years or older receiving care at a participating clinic as a long-term resident who consented to data and specimen collection. Exclusion criteria consisted of pregnancy and/or imprisonment. Screen-positive syphilis was defined as a reactive rapid plasma regain (RPR) upon study enrollment whereas confirmed syphilis included a reactive RPR followed by reactive treponemal test. Multivariate analyses was performed to determine HIV and syphilis co-infection risk factors. RESULTS: Between 2013 and March 1, 2020, 2939 PLWH enrolled and 2818 were included for analysis. Screen-positive and confirmed syphilis prevalence were 5.3% (151/2818) and 3.1% (87/2818), respectively. When the analysis was restricted to PLWH with an RPR titer of greater than, or equal to, 1:8, 11/87 (12.6%) participants were included. No PLWH and confirmed syphilis had documented genital ulcers. In the multivariate model, participants with confirmed syphilis co-infection were more likely to have none or some primary education [aOR 3.29 (1.60, 6.74)] and consume alcohol [aOR 1.87 (1.16, 3.03)] compared to those without syphilis. Antiretroviral therapy (ART) with suppressed viral load (VL) was protective in the unadjusted model but not adjusted multivariate model. CONCLUSIONS: Our findings show that syphilis rates in sub-Saharan Africa remain elevated where diagnosis remains challenging, and that both lower education level and alcohol consumption are significantly associated with HIV/syphilis co-infection in AFRICOS. Based on our analysis, current STI guidelines targeting testing for African individuals with either new HIV diagnosis or syndromic symptoms may be inadequate, highlighting the need for increased testing and treatment strategies in resource-limited settings.

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

BACKGROUND: Support groups for people living with HIV (PLWH) may improve HIV care adherence and outcomes. We assessed the impact of support group attendance on antiretroviral therapy (ART) adherence and viral suppression in four African countries. METHODS: The ongoing African Cohort Study (AFRICOS) enrolls participants at 12 clinics in Kenya, Uganda, Tanzania, and Nigeria. Self-reported attendance of any support group meetings, self-reported ART adherence, and HIV RNA are assessed every 6 months. Logistic regression models with generalized estimating equations were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) for support group attendance and other factors potentially associated with ART adherence and viral suppression. RESULTS: From January 2013 to December 1, 2019, 1959 ART-experienced PLWH were enrolled and 320 (16.3%) reported any support group attendance prior to enrollment. Complete ART adherence, with no missed doses in the last 30 days, was reported by 87.8% while 92.4% had viral suppression <1000copies/mL across all available visits. There was no association between support group attendance and ART adherence in unadjusted (OR 1.01, 95% CI 0.99-1.03) or adjusted analyses (aOR 1.00, 95% CI 0.98-1.02). Compared to PLWH who did not report support group attendance, those who did had similar odds of viral suppression in unadjusted (OR 0.99, 95% CI 0.978-1.01) and adjusted analyses (aOR 0.99, 95% CI 0.97-1.01). CONCLUSION: Support group attendance was not associated with significantly improved ART adherence or viral suppression, although low support group uptake may have limited our ability to detect a statistically significant impact.