Comparison of nucleocapsid and spike antibody ELISAs for determining SARS-CoV-2 seropositivity in Kenyan women and infants.

A multitude of enzyme-linked immunosorbent assays (ELISAs) has been developed to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies since the coronavirus disease 2019 pandemic started in late 2019. Assessing the reliability of these assays in diverse global populations is critical. This study compares the use of the commercially available Platelia Total Ab Assay (Bio-Rad) nucleocapsid ELISA to the widely used Mount Sinai spike IgG ELISA in a Kenyan population seroprevalence study. Using longitudinal plasma specimens collected from a mother-infant cohort living in Nairobi, Kenya between May 2019 and December 2020, this study demonstrates that the two assays have a high qualitative agreement (92.7%) and strong correlation of antibody levels (R2 = 0.973) in repeated measures. Within this cohort, seroprevalence detected by either ELISA closely resembled previously published seroprevalence estimates for Kenya during the sampling period and no significant difference in the incidence of SARS-CoV-2 antibody detection by either assay was observed. Assay comparability was not affected by HIV exposure status. These data support the use of the Platelia SARS-CoV-2 Total Ab ELISA as a suitable high-throughput method for seroprevalence studies in Kenya.

Low prevalence of bacterial vaginosis in Kenyan adolescent girls and rapid incidence after first sex.

BACKGROUND: Bacterial vaginosis is a risk factor for sexually transmitted infections, including HIV. Adult African women have a high prevalence of bacterial vaginosis, but it is not known when first bacterial vaginosis occurs. OBJECTIVE: This study aimed to describe bacterial vaginosis in younger African women, before and after first sex, and to determine the incidence of bacterial vaginosis and significant correlates of bacterial vaginosis incidence and recurrence. STUDY DESIGN: In a prospective observational cohort study enrolling adolescents with limited sexual experience, young women aged 16 to 21 years were recruited in Thika, Kenya. Eligible participants were HIV and herpes simplex virus 2 seronegative and reported 0 or 1 lifetime sexual partner. The Nugent score was determined at quarterly visits from vaginal Gram stains. The trends in bacterial vaginosis were described over time; hazard ratios were calculated using Cox regression, and relative risk of bacterial vaginosis was estimated using generalized estimating equations and Poisson regression. RESULTS: A total of 400 participants with a median age of 18.6 years (interquartile range, 16-21) were enrolled. Of note, 322 participants (80.5%) reported no history of sex, whereas 78 participants (19.5%) reported sex with 1 partner. At enrollment, bacterial vaginosis (Nugent score of ≥7) was uncommon (21/375 [5.6%]). Overall, 144 participants had bacterial vaginosis at least once, for an incidence rate of 16.5 cases per 100 person-years. Before first sex, bacterial vaginosis was present at 2.8% of visits, compared with 13.7% of visits after first sex. An adjusted model of bacterial vaginosis incidence observed that first sex was associated with more than a 2-fold increased bacterial vaginosis risk (adjusted hazard ratio, 2.44; 95% confidence interval, 1.25-4.76; P=.009). Chlamydia diagnosis (adjusted hazard ratio, 1.73; 95% confidence interval, 1.1-2.8; P=.02), and herpes simplex virus 2 seropositivity (adjusted hazard ratio, 2.88; 95% confidence interval, 1.17-7.09; P=.021) were both associated with incident bacterial vaginosis. A multivariate generalized estimating equation model, including all episodes of bacterial vaginosis, demonstrated risk factors, including first sex, sexually transmitted infections, urban residence, recent sex, and no income; the most important risk factor was first sex (adjusted relative risk, 1.92; 95% confidence interval, 1.12-3.31; P=.018). The probability of bacterial vaginosis increased with each subsequent episode; mean Nugent scores increased after each bacterial vaginosis episode. CONCLUSION: Using detailed longitudinal observation, this study found that Kenyan adolescents have almost no bacterial vaginosis before first sex and that initiation of sexual activity was the strongest risk factor for both prevalent bacterial vaginosis and incident bacterial vaginosis.

SARS-CoV-2 antibody prevalence, correlates, and access to harm reduction services among people who inject drugs living with and without HIV and their partners in Kenya.

BACKGROUND: In sub-Saharan Africa many people who inject drugs (PWID) are living with undiagnosed or untreated HIV and experience high levels of poverty and conditions that can contribute to worse outcomes from SARS-CoV-2 infection. Identifying the burden of SARS-CoV-2 infection in marginalized populations like PWID may contribute to controlling the pandemic. METHODS: This is a nested cross-sectional study within an ongoing cohort study that recruits PWID living with HIV and their injecting and/or sexual partners at needle and syringe program sites and methadone clinics in Kenya. Blood samples were collected from consenting participants at enrollment to determine SARS-CoV-2 antibodies using a Platellia BioRad SARS-CoV-2 total antibody enzyme-linked immunosorbent assay. Baseline data were collected on HIV status, antiretroviral therapy and methadone adherence. We used logistic regression to identify factors associated with antibody positivity and descriptive statistics to report SARS-CoV-2 antibody prevalence. RESULTS: One thousand participants were enrolled between April and July 2021, of whom 323 (32.3%) were women and 677 (67.7%) were men. Median age of participants was 36 years (interquartile range: 30, 42). SARS-CoV-2 antibody positivity was found in 309 (30.9%) participants. Disruption in obtaining methadone service was reported by 106 (24.3%) of the participants. Men were significantly less likely than women to have SARS-CoV-2 antibodies (adjusted odds ratio [aOR] = 0.68, 95% confidence interval [CI] 0.51, 0.95; p < 0.01) Participants who reported a sexual or injecting partner diagnosed with SARS-CoV-2 were twofold more likely to have SARS-CoV-2 antibodies detected (aOR = 2.21, 95% CI 1.06, 4.58; p < 0.032). Living with HIV was not associated with presence of SARS-CoV-2 antibodies. CONCLUSION: The seroprevalence of SARS-CoV-2 of 30.9% in this cohort suggests high transmission rates within this population. SARS-CoV-2 seroprevalence was similar for people living with and without HIV. A large portion of this population was noted to have had disruption in access to harm reduction services.

Antenatal depressive symptoms in Kenyan women living with HIV: contributions of recent HIV diagnosis, stigma, and partner violence.

Depression among pregnant women living with HIV (WLWH) in sub-Saharan Africa leads to poor pregnancy and HIV outcomes. This cross-sectional analysis utilized enrollment data from a randomized trial (Mobile WAChX, NCT02400671) in six Kenyan public maternal and child health clinics. Depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9), stigma with the Stigma Scale for Chronic Illness, and intimate partner violence (IPV) with the Abuse Assessment Screen. Correlates of moderate-to-severe depressive symptoms ("depression", PHQ-9 score ≥10) were assessed using generalized estimating equation models clustered by facility. Among 824 pregnant WLWH, 9% had depression; these women had more recent HIV diagnosis than those without depression (median 0.4 vs. 2.0 years since diagnosis, p = .008). Depression was associated with HIV-related stigma (adjusted Prevalence Ratio [aPR]:2.36, p = .025), IPV (aPR:2.93, p = .002), and lower social support score (aPR:0.99, p = .023). Using population-attributable risk percent to estimate contributors to maternal depression, 81% were attributable to stigma (27%), recent diagnosis (24%), and IPV (20%). Integrating depression screening and treatment in prevention of mother-to-child HIV transmission programs may be beneficial, particularly in women recently diagnosed or reporting stigma and IPV.

Characteristics associated with HIV and hepatitis C seroprevalence among sexual and injecting partners of HIV positive persons who inject drugs in Nairobi and coastal Kenya.

BACKGROUND: Persons who inject drugs (PWID) have higher HIV and hepatitis C virus (HCV) seroprevalence than the general population in many parts of sub-Saharan Africa (SSA). The seroprevalences of HIV and HCV are also higher in coastal Kenya than in Nairobi. Understanding drivers of regional HIV and HCV variation among PWID in Kenya may inform population-specific prevention interventions. METHODS: Using a cross-sectional study, we defined HIV and HCV seroprevalence among persons identified as sexual or injecting partners of HIV positive PWID in two regions of Kenya and used logistic regression to identify demographic and behavioral characteristics associated with higher seroprevalence. RESULTS: Among 2386 partners, 469 (19.7%) tested HIV positive and 297(12.4%) tested HCV antibody positive. Partners on the Coast were more likely to live with HIV (seroprevalences: Coast = 23.8%, Nairobi = 17.1%; p < 0.001) and be HCV antibody positive (seroprevalences: Coast = 17.0%, Nairobi = 8.6%; p < 0.001). After adjusting for sex, age, and years injecting and accounting for clustering by site, the higher prevalence of both diseases in the Coast remained significant for HIV (OR 1.68, 95% CI 1.13-2.51) but not for HCV (OR 1.72, 95% CI 0.84-3.74). Compared to those recruited in Nairobi, partners on the Coast were older (Coast = 35 years, Nairobi = 31 years; p < 0.001), more likely to be male (Coast = 77.6%, Nairobi = 61.7%; p < 0.001), to have paid (Coast = 59.2%, Nairobi = 32.8%; p < 0.001) or received (Coast = 44.2%, Nairobi 35.4%; p < 0.001) money for sex, or to have had sex with someone they knew to be HIV positive (Coast 22.0%, Nairobi 10.8%; p < 0.001). Partners who had injected for five or more years had 1.48 times greater odds (95% CI 1.20-1.82) of living with HIV compared to partners who injected less than 5 years and more than twice the odds of HCV (95% CI 1.84-4.11). CONCLUSION: HIV and HCV seroprevalence among sexual and injecting partners of PWID was, respectively, 5 times and > 12 times greater than is reported among the general population in Kenya (4% and < 1%, respectively). Providing resources and education will be crucial to reduce exposure and to maintain the lower needle and equipment sharing that we observed compared to other studies.

Influence of Intramuscular Depot Medroxyprogesterone Acetate Initiation on Vaginal Microbiota in the Postpartum Period.

BACKGROUND: The vaginal microbiome plays a key role in women's reproductive health. Use of exogenous hormones, such as intramuscular depot medroxyprogesterone acetate (DMPA-IM), may alter the composition of vaginal bacterial community. METHODS: Vaginal swab samples were collected from postpartum Kenyan women initiating DMPA-IM or nonhormonal contraception (non-HC). Bacterial vaginosis was assessed by Nugent score (Nugent-BV) and bacterial community composition was evaluated using broad-range 16S ribosomal RNA gene polymerase chain reaction with high-throughput sequencing. Changes in Nugent score, alpha diversity (Shannon diversity index), and total bacterial load between contraceptive groups from enrollment to 3 months after initiation were estimated using multivariable linear mixed effects regression. RESULTS: Among 54 human immunodeficiency virus-negative women, 33 choosing DMPA-IM and 21 choosing non-HC, Nugent-BV was more common among DMPA-IM users at enrollment. At follow-up, Nugent score had decreased significantly among DMPA-IM users (change, -1.89; 95% confidence interval [CI], -3.53 to -.25; P = .02) while alpha diversity remained stable (0.03; -.24 to .30; P = .83). Conversely, Nugent score remained relatively stable among non-HC users (change, -0.73; 95% CI, -2.18 to .73; P = .33) while alpha diversity decreased (-0.34; -.67 to -.001; P = .05). The total bacterial load decreased slightly in DMPA-IM users and increased slightly among non-HC users, resulting in a significant difference in change between the contraceptive groups (difference, -0.64 log10 gene copies per swab sample; 95% CI, -1.19 to -.08; P = .02). While significant changes in Nugent score and alpha diversity were observed within contraceptive groups, changes between groups were not significantly different. CONCLUSIONS: Postpartum vaginal bacterial diversity did not change in DMPA-IM users despite a reduction in Nugent-BV, but it decreased significantly among women using non-HC. Choice of contraception may influence Lactobacillus recovery in postpartum women.

Human Immunodeficiency Virus Is Associated With Higher Levels of Systemic Inflammation Among Kenyan Adults Despite Viral Suppression.

BACKGROUND: Systemic inflammation independently predicts future cardiovascular events and is associated with a 2-fold increase in cardiovascular disease (CVD) risk among persons living with human immunodeficiency virus (PLHIV). We examined the association between inflammatory markers, HIV status, and traditional CVD risk factors. METHODS: We conducted a cross-sectional study of Kenyan adults with and without HIV seeking care at Kisumu County Hospital. Using a multiplex immunoassay, we measured interleukin (IL) 1ß, IL-6, tumor necrosis factor α (TNF-α), and high-sensitivity C-reactive protein (hsCRP) concentrations. We compared inflammatory marker concentrations by HIV status using the Wilcoxon rank-sum test. Multivariable linear regression was used to evaluate associations between inflammatory biomarkers and HIV status, adjusting for CVD risk factors. RESULTS: We enrolled 286 PLHIV and 277 HIV-negative participants. Median duration of antiretroviral therapy for PLHIV was 8 years (interquartile range, 4-10) and 96% were virally suppressed. PLHIV had a 51% higher mean IL-6 concentration (P < .001), 39% higher mean IL-1ß (P = .005), 40% higher mean TNF-α (P < .001), and 27% higher mean hsCRP (P = .008) compared with HIV-negative participants, independent of CVD risk factors. Male sex, older age, and obesity were associated with higher concentrations of inflammatory markers. Restricting to PLHIV, viral load of ≥1000 copies/mL was associated with higher TNF-α levels (P = .013). CONCLUSIONS: We found higher levels of systemic inflammatory biomarkers among PLHIV who were virally suppressed, and this was independent of traditional CVD risk factors. Further longitudinal analyses to determine whether these inflammatory markers predict future CVD events, and are possible therapeutic targets among PLHIV, are warranted.

SMS messaging to improve retention and viral suppression in prevention of mother-to-child HIV transmission (PMTCT) programs in Kenya: A 3-arm randomized clinical trial.

BACKGROUND: Pregnant and postpartum women living with HIV (WLWH) need support for HIV and maternal child health (MCH) care, which could be provided using short message service (SMS). METHODS AND FINDINGS: We compared 2-way (interactive) and 1-way SMS messaging to no SMS in a 3-arm randomized trial in 6 MCH clinics in Kenya. Messages were developed using the Health Belief Model and Social Cognitive Theory; HIV messages were integrated into an existing MCH SMS platform. Intervention participants received visit reminders and prespecified weekly SMS on antiretroviral therapy (ART) adherence and MCH, tailored to their characteristics and timing. Two-way participants could message nurses as needed. Clinic attendance, viral load (VL), and infant HIV results were abstracted from program records. Primary outcomes were viral nonsuppression (VL ≥1,000 c/ml), on-time clinic attendance, loss to follow-up from clinical care, and infant HIV-free survival. Among 824 pregnant women randomized between November 2015 and May 2017, median age was 27 years, gestational age was 24.3 weeks, and time since initiation of ART was 1.0 year. During follow-up to 2 years postpartum, 9.8% of 3,150 VL assessments and 19.6% of women were ever nonsuppressed, with no significant difference in 1-way versus control (11.2% versus 9.6%, adjusted risk ratio (aRR) 1.02 [95% confidence interval (CI) 0.67 to 1.54], p = 0.94) or 2-way versus control (8.5% versus 9.6%, aRR 0.80 [95% CI 0.52 to 1.23], p = 0.31). Median ART adherence and incident ART resistance did not significantly differ by arm. Overall, 88.9% (95% CI 76.5 to 95.7) of visits were on time, with no significant differences between arms (88.2% in control versus 88.6% in 1-way and 88.8% in 2-way). Incidence of infant HIV or death was 3.01/100 person-years (py), with no significant difference between arms; risk of infant HIV infection was 0.94%. Time to postpartum contraception was significantly shorter in the 2-way arm than control. Study limitations include limited ability to detect improvement due to high viral suppression and visit attendance and imperfect synchronization of SMS reminders to clinic visits. CONCLUSIONS: Integrated HIV/MCH messaging did not improve HIV outcomes but was associated with improved initiation of postpartum contraception. In programs where most women are virally suppressed, targeted SMS informed by VL data may improve effectiveness. Rigorous evaluation remains important to optimize mobile health (mHealth) interventions. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02400671.

Pooled testing for SARS-CoV-2, options for efficiency at scale.

Widescale testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is recognized as a key element of surveillance and outbreak control in the coronavirus disease 2019 (COVID-19) pandemic. The practical challenges, however, have often led to testing only symptomatic individuals and their close contacts. As many countries plan for a cautious relaxation of social restrictions, more effective approaches for widescale testing are increasingly important. Early in the COVID-19 pandemic, laboratories in several countries demonstrated the feasibility of detecting SARS-CoV-2 infection by pooled testing, which combines the specimens from several individuals. Since no further testing is needed for individuals in a negative pool, there is potential for greater efficiency of testing. Despite validations of the accuracy of the results and the efficiency in testing specific groups, the benefits of pooling are less acknowledged as a population surveillance strategy that can detect new disease outbreaks without posing restrictions on entire societies. Pooling specimens from natural clusters, such as school classes, sports teams, workplace colleagues and other social networks, would enable timely and cost-effective widescale testing for SARS-CoV-2. The initial result would be readily translatable into action in terms of quarantine and isolation policies. Clusters of uninfected individuals would be quickly identified and immediate local lockdown of positive clusters would be the appropriate and sufficient action while retesting those individuals. By adapting to the social networks of a population, pooled testing offers a cost-efficient surveillance system that is synchronized with quarantine policies that are rational, risk-based and equitable.

Le dépistage à grande échelle de l'infection au coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2) est considéré comme l'un des piliers de la surveillance et de la lutte contre la pandémie de maladie à coronavirus 2019 (COVID-19). Néanmoins, les défis pratiques inhérents à ce dépistage ont souvent poussé à ne tester que les individus symptomatiques et leurs contacts rapprochés. Alors que de nombreux pays prévoient de lever certaines restrictions sociales, il devient de plus en plus important d'adopter des approches plus efficaces pour dépister à grande échelle. Dès le début de la pandémie de COVID-19, des laboratoires répartis dans divers pays ont démontré qu'il était possible de détecter une infection au SARS-CoV-2 par le biais de tests groupés, qui rassemblent des échantillons provenant de plusieurs individus. Si le résultat de l'un des groupes est négatif, nul besoin de tester chaque individu, ce qui pourrait accroître considérablement l'efficacité du processus. Même si les résultats se sont révélés fiables et que le dépistage de groupes spécifiques a prouvé l'efficacité du système, le regroupement d'échantillons est rarement envisagé comme stratégie de surveillance de la population permettant d'identifier toute nouvelle flambée des contaminations sans imposer de restrictions à l'ensemble de la société. Pourtant, le regroupement d'échantillons provenant de foyers épidémiques naturels tels que les salles de classe, les équipes sportives, les collègues de travail et autres interactions sociales ferait gagner du temps et de l'argent lors du dépistage à grande échelle du SARS-CoV-2. Le résultat initial pourrait aussitôt se traduire par des mesures d'isolation et de quarantaine. Les groupes d'individus non infectés seraient rapidement repérés, et le confinement immédiat des groupes positifs constituerait une intervention appropriée et suffisante pendant que ces individus subiraient un nouveau test. En s'adaptant aux interactions sociales d'une population donnée, les tests groupés représentent une solution de surveillance rentable en phase avec une politique de quarantaine rationnelle, équitable et fondée sur une analyse des risques.

Las pruebas a gran escala para detectar la infección por el coronavirus del síndrome respiratorio agudo grave-2 (SARS-CoV-2) se reconocen como un elemento clave de la vigilancia y el control de los brotes de la pandemia por enfermedad del coronavirus (COVID-19). Sin embargo, los desafíos prácticos han llevado a menudo a realizar pruebas solo a las personas sintomáticas y a sus contactos cercanos. A medida que muchos países planifican una cautelosa relajación de las restricciones sociales, es cada vez más importante contar con enfoques más eficaces para la realización de pruebas a gran escala. Al principio de la pandemia de COVID-19, los laboratorios de varios países demostraron la viabilidad de la detección de la infección por el SARS-CoV-2 mediante pruebas conjuntas, que combinan las muestras de varias personas. Dado que no se necesitan más pruebas para las personas en un grupo negativo, existe la posibilidad de que las pruebas sean más eficaces. A pesar de las validaciones de la exactitud de los resultados y la eficiencia en las pruebas de grupos específicos, los beneficios de la agrupación son menos reconocidos como una estrategia de vigilancia de la población que puede detectar nuevos brotes de la enfermedad sin plantear restricciones en sociedades enteras. La puesta en común de muestras procedentes de grupos naturales, como clases escolares, equipos deportivos, compañeros de trabajo y otras redes sociales, permitiría realizar pruebas a gran escala, oportunas y rentables, para detectar el SARS-CoV-2. El resultado inicial permitiría ejecutar fácilmente políticas de cuarentena y aislamiento. Se identificarían rápidamente los grupos de personas no infectadas y bastaría con una cuarentena inmediata de los grupos positivos mientras se vuelven a realizar las pruebas a dichas personas. Al adaptarse a las redes sociales de una población, las pruebas conjuntas ofrecen un sistema de vigilancia rentable que se sincroniza con políticas de cuarentena que son racionales, basadas en el riesgo y equitativas.

Prevalence of Pre-antiretroviral-Treatment Drug Resistance by Gender, Age, and Other Factors in HIV-Infected Individuals Initiating Therapy in Kenya, 2013-2014.

Background: Pre-antiretroviral-treatment drug resistance (PDR) is a predictor of human immunodeficiency virus (HIV) treatment failure. We determined PDR prevalence and correlates in a Kenyan cohort. Methods: We conducted a cross-sectional analysis of antiretroviral (ARV) treatment-eligible HIV-infected participants. PDR was defined as ≥2% mutant frequency in a participant's HIV quasispecies at pol codons K103N, Y181C, G190A, M184 V, or K65R by oligonucleotide ligation assay and Illumina sequencing. PDR prevalence was calculated by demographics and codon, stratifying by prior ARV experience. Poisson regression was used to estimate prevalence ratios. Results: PDR prevalences (95% confidence interval [CI]) in 815 ARV-naive adults, 136 ARV-experienced adults, and 36 predominantly ARV-naive children were 9.4% (7.5%-11.7%), 12.5% (7.5%-19.3%), and 2.8% (0.1%-14.5%), respectively. Median mutant frequency within an individual's HIV quasispecies was 67%. PDR prevalence in ARV-naive women 18-24 years old was 21.9% (9.3%-40.0%). Only age in females associated with PDR: A 5-year age decrease was associated with adjusted PDR prevalence ratio 1.20 (95% CI, 1.06-1.36; P = .004). Conclusions: The high PDR prevalence may warrant resistance testing and/or alternative ARVs in high HIV prevalence settings, with attention to young women, likely to have recent infection and higher rates of resistance. Clinical Trials Registration: NCT01898754.

Real-world performance of point-of-care vs. standard-of-care HIV viral load testing in western Kenya: Secondary analysis of Opt4Kids and Opt4Mamas studies.

Routine HIV viral load testing is important for evaluating HIV treatment outcomes, but conventional viral load testing has many barriers including expensive laboratory equipment and lengthy results return times to patients. A point-of-care viral load testing technology, such as GeneXpert HIV-1 quantification assay, could reduce these barriers by decreasing cost and turnaround time, however real-world performance is limited. We conducted a secondary analysis using 900 samples collected from participants in two studies to examine the performance of GeneXpert as point-of-care viral load compared to standard-of-care testing (which was conducted with two centralized laboratories using traditional HIV-1 RNA PCR quantification assays). The two studies, Opt4Kids (n = 704 participants) and Opt4Mamas (n = 820 participants), were conducted in western Kenya from 2019-2021 to evaluate the effectiveness of a combined intervention strategy, which included point-of-care viral load testing. Paired viral load results were compared using four different thresholds for virological non-suppression, namely ≥50, ≥200, ≥400, ≥1000 copies/ml. At a threshold of ≥1000 copies/mL, paired samples collected on the same day: demonstrated sensitivities of 90.0% (95% confidence interval [CI] 68.3, 98.8) and 66.7% (9.4, 99.2), specificities of 98.4% (95.5, 99.7) and 100% (96.5, 100), and percent agreements of 97.7% (94.6, 99.2) and 99.1% (95.0, 100) in Opt4Kids and Opt4Mamas studies, respectively. When lower viral load thresholds were used and the paired samples were collected an increasing number of days apart, sensitivity, specificity, and percent agreement generally decreased. While specificity and percent agreement were uniformly high, sensitivity was lower than expected. Non-specificity of the standard of care testing may have been responsible for the sensitivity values. Nonetheless, our results demonstrate that GeneXpert may be used reliably to monitor HIV treatment in low- and middle- income countries to attain UNAID's 95-95-95 HIV goals.

Gut virome and microbiome dynamics before and after SARS-CoV-2 infection in women living with HIV and their infants.

Microbiome perturbations can have long-term effects on health. The dynamics of the gut microbiome and virome in women living with HIV (WLHIV) and their newborn infants is poorly understood. Here, we performed metagenomic sequencing analyses on longitudinal stool samples including 23 mothers (13 WLHIV, 10 HIV-negative) and 12 infants that experienced SARS-CoV-2 infection with mild disease, as well as 40 mothers (18 WLHIV, 22 HIV-negative) and 60 infants that remained SARS-CoV-2 seronegative throughout the study follow-up. Regardless of HIV or SARS-CoV-2 status, maternal bacterial and viral profiles were distinct from infants. Using linear mixed effects models, we showed that while the microbiome alpha diversity trajectory was not significantly different between SARS-CoV-2 seropositive and seronegative women. However, seropositive women's positive trajectory while uninfected was abruptly reversed after SARS-CoV-2 infection (p = 0.015). However, gut virome signatures of women were not associated with SARS-CoV-2. Alterations in infant microbiome and virome diversities were generally not impacted by SARS-CoV-2 but were rather driven by development. We did not find statistically significant interactions between HIV and SARS-CoV-2 on the gut microbiome and virome. Overall, our study provides insights into the complex interplay between maternal and infant bacterial microbiome, virome, and the influence of SARS-CoV-2 and HIV status.

Gut virome and microbiome dynamics before and after SARS-CoV-2 infection in women living with HIV and their infants.

Microbiome perturbations can have long-term effects on health. The dynamics of the gut microbiome and virome in women living with HIV (WLHIV) and their newborn infants is poorly understood. Here, we performed metagenomic sequencing analyses on longitudinal stool samples including 23 mothers (13 WLHIV, 10 HIV-negative) and 12 infants that experienced SARS-CoV-2 infection with mild disease, as well as 40 mothers (18 WLHIV, 22 HIV-negative) and 60 infants that remained SARS-CoV-2 seronegative throughout the study follow-up. Regardless of HIV or SARS-CoV-2 status, maternal bacterial and viral profiles were distinct from infants. Using linear mixed effects models, we showed that the microbiome alpha diversity trajectory was not significantly different between SARS-CoV-2 seropositive and seronegative women. However, seropositive women's positive trajectory while uninfected was abruptly reversed after SARS-CoV-2 infection (p = 0.015). Gut virome signatures of women were not associated with SARS-CoV-2. Alterations in infant microbiome and virome diversities were generally not impacted by SARS-CoV-2 but were rather driven by development. We did not find statistically significant interactions between HIV and SARS-CoV-2 on the gut microbiome and virome. Overall, our study provides insights into the complex interplay between maternal and infant bacterial microbiome, virome, and the influence of SARS-CoV-2 and HIV status.

Virologic Nonsuppression and HIV Drug Resistance Among People Who Inject Drugs and Their Sexual and Injecting Partners in Kenya.

We evaluated the prevalence and correlates of HIV viral nonsuppression and HIV drug resistance (HIV-DR) in a cohort of people who inject drugs living with HIV (PWID-LH) and their sexual and injecting partners living with HIV in Kenya. HIV-DR testing was performed on participants with viral nonsuppression. Of 859 PWID-LH and their partners, 623 (72.5%) were on antiretroviral therapy (ART) ≥4 months and 148/623 (23.8%) were not virally suppressed. Viral nonsuppression was more common among younger participants and those on ART for a shorter duration. Among 122/148 (82.4%) successfully sequenced samples, 55 (45.1%) had detectable major HIV-DR mutations, mainly to non-nucleoside and nucleotide reverse transcriptase inhibitors (NNRTI and NRTI). High levels of HIV-DR among those with viral nonsuppression suggests need for viral load monitoring, adherence counseling, and timely switching to alternate ART regimens in this key population.

Efficacy of assisted partner services for people who inject drugs in Kenya to identify partners living with HIV and hepatitis C virus infection: a prospective cohort study.

BACKGROUND: People who inject drugs are at increased risk of both HIV and hepatitis C virus (HCV) infections but face barriers to testing and engagement in care. Assisted partner services are effective in locating people with HIV but are understudied among people who inject drugs. We assessed whether assisted partner services could be used to find, test for HIV and HCV infections, and link to care the partners of people who inject drugs in Kenya. METHODS: In this prospective study at eight sites offering harm-reduction services in Kenya, we enrolled people aged 18 years or older who inject drugs and were living with HIV (index participants) between Feb 27, 2018, and Nov 1, 2021. Index participants provided information about their sexual and injecting partners (ie, anyone with whom they had had sexual intercourse or injected drugs in the previous 3 years), and then community-embedded peer educators located partners and referred them for enrolment in the study (partner participants). All participants underwent testing for HCV infection, and partner participants also underwent HIV testing. Index and partner participants with HIV but who were not on antiretroviral therapy (ART) were linked with treatment services, and those positive for HCV were linked to treatment with direct-acting antivirals. We calculated the number of index participants whom we needed to interview to identify partner participants with HIV and HCV infection. FINDINGS: We enrolled 989 people living with HIV who inject drugs, who mentioned 4705 sexual or injecting partners. Of these 4705 partners, we enrolled 4597 participants, corresponding to 3323 unique individuals. 597 (18%) partner participants had HIV, of whom 506 (85%) already knew their status. 358 (71%) of those who knew they were HIV positive were virally suppressed. 393 (12%) partner participants were HCV antibody positive, 213 (54%) of whom had viraemia and 104 (26%) of whom knew their antibody status. 1·66 (95% CI 1·53-1·80) index participants had to be interviewed to identify a partner with HIV, and 4·24 (3·75-4·85) had to be interviewed to find a partner living with HIV who was unaware of their HIV status, not on ART, or not virally suppressed. To find a partner seropositive for HCV who did not know their antibody status, 3·47 (3·11-3·91) index participants needed to be interviewed. Among the 331 index and partner participants living with HIV who were not on ART at enrolment, 238 (72%) were taking ART at 6-month follow-up. No adverse events were attributed to study procedures. INTERPRETATION: Use of assisted partner services among people with HIV who inject drugs was safe and identified partners with HIV and HCV infections. Assisted partner services was associated with increased uptake of ART for both index participants and partners. FUNDING: US National Institutes of Health.

Longitudinal dynamics of the nasopharyngal microbiome in response to SARS-CoV-2 Omicron variant and HIV infection in Kenyan women and their infants.

The nasopharynx and its microbiota are implicated in respiratory health and disease. The interplay between viral infection and the nasopharyngeal microbiome is an area of increased interest and of clinical relevance. The impact of SARS-CoV-2, the etiological agent of the Coronavirus Disease 2019 (COVID-19) pandemic, on the nasopharyngeal microbiome, particularly among individuals living with HIV, is not fully characterized. Here we describe the nasopharyngeal microbiome before, during and after SARS-CoV-2 infection in a longitudinal cohort of Kenyan women (21 living with HIV and 14 HIV-uninfected) and their infants (18 HIV-exposed, uninfected and 18 HIV-unexposed, uninfected), followed between September 2021 through March 2022. We show using genomic epidemiology that mother and infant dyads were infected with the same strain of the SARS-CoV-2 Omicron variant that spread rapidly across Kenya. Additionally, we used metagenomic sequencing to characterize the nasopharyngeal microbiome of 20 women and infants infected with SARS-CoV-2, 6 infants negative for SARS-CoV-2 but experiencing respiratory symptoms, and 34 timepoint matched SARS-CoV-2 negative mothers and infants. Since individuals were sampled longitudinally before and after SARS-CoV-2 infection, we could characterize the short- and long-term impact of SARS-CoV-2 infection on the nasopharyngeal microbiome. We found that mothers and infants had significantly different microbiome composition and bacterial load (p-values <.0001). However, in both mothers and infants, the nasopharyngeal microbiome did not differ before and after SARS-CoV-2 infection, regardless of HIV-exposure status. Our results indicate that the nasopharyngeal microbiome is resilient to SARS-CoV-2 infection and was not significantly modified by HIV.

Bacterial vaginosis-driven changes in vaginal T cell phenotypes and their implications for HIV susceptibility.

Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome that is prevalent in reproductive-age women worldwide. Adverse outcomes associated with BV include an increased risk of sexually acquired Human Immunodeficiency Virus (HIV), yet the immunological mechanisms underlying this association are not well understood. To investigate BV driven changes to cervicovaginal tract (CVT) and circulating T cell phenotypes, participants with or without BV provided vaginal tract (VT) and ectocervical (CX) tissue biopsies and peripheral blood mononuclear cells (PBMC). Immunofluorescence analysis of genital mucosal tissues revealed a reduced density of CD3+CD4+CCR5+ cells in the VT lamina propria of individuals with compared to those without BV (median 243.8 cells/mm2 BV- vs 106.9 cells/mm2 BV+, p=0.043). High-parameter flow cytometry of VT biopsies revealed an increased frequency in individuals with compared to those without BV of dysfunctional CD39+ conventional CD4+ T cells (Tconv) (median frequency 15% BV- vs 30% BV+, padj=0.0331) and tissue-resident CD69+CD103+ Tconv (median frequency 24% BV- vs 38% BV+, padj=0.0061), previously reported to be implicated in HIV acquisition and replication. Our data suggests that BV elicits diverse and complex VT T cell alterations and expands on potential immunological mechanisms that may promote adverse outcomes including HIV susceptibility.

First Case of HIV Seroconversion With Integrase Resistance Mutations on Long-Acting Cabotegravir for Prevention in Routine Care.

Background: Long-acting cabotegravir (CAB-LA) is highly effective for HIV prevention, but delayed HIV diagnoses and integrase strand transfer inhibitor (INSTI) resistance were observed in trials. We report the first case in routine clinical care of HIV infection on CAB-LA with INSTI resistance. Methods: The SeroPrEP study enrolls individuals in the United States who acquire HIV on pre-exposure prophylaxis modalities to assess diagnostics, antiretroviral (ARV) drug levels, resistance, and treatment outcomes. Resistance mutations in full-length HIV-1 integrase were identified by single-genome sequencing (SGS). Cabotegravir concentrations in plasma and hair segments were measured by liquid chromatography-tandem mass spectrometry. Results: A 23-year-old gender-nonbinary person, male at birth, restarted CAB-LA 6 months after discontinuation due to losing insurance. Prior to restart, HIV-1 RNA was not detected, but 20 days elapsed before CAB-LA injection. After the second CAB-LA injection, HIV antigen/antibody returned reactive (HIV-1 RNA 451 copies/mL). SGS of plasma HIV-1 RNA identified INSTI mutation Q148R in 2/24 sequences 2 days postdiagnosis; commercial genotype failed amplification. Cabotegravir hair concentration was 0.190 ng/mg 2 weeks prediagnosis; plasma cabotegravir was high (3.37 µg/mL; ∼20× PA-IC90) 14 days postdiagnosis. Viral suppression was maintained for 6 months on darunavir/cobicistat/emtricitabine/tenofovir alafenamide, then switched to doravirine + emtricitabine/tenofovir alafenamide due to nausea. Conclusions: In this first case of HIV infection on CAB-LA with INSTI resistance in routine care, cabotegravir resistance was detected only with a sensitive research assay. Accelerated pathways to minimize time between HIV testing and CAB-LA initiation are needed to optimize acute HIV detection and mitigate resistance risk. Sustained product access regardless of insurance is imperative to reduce HIV infections on CAB-LA.

Longitudinal assessment of bacterial vaginosis prior to and during incident pregnancy: an observational study in Kenyan adolescent girls and young women.

OBJECTIVE: To determine bacterial vaginosis (BV) status at multiple time points among adolescent girls and young women (AGYW) and assess the impact of pregnancy on their BV status. DESIGN: Longitudinal cohort study. SETTING: Thika, Kenya. PARTICIPANTS: AGYW aged 16-20 years enrolled prior to first sex or reporting only a single lifetime partner. MAIN OUTCOME MEASURES: The primary outcome was relative risk (RR) of BV during pregnancy compared with before pregnancy by analysing longitudinal trends in BV over time. BV risk was estimated using Poisson regression models. RESULTS: A total of 121 AGYW became pregnant in the parent cohort and had BV results before, during or after pregnancy. Point prevalence of BV was 11.0% at visits >12 months pre-pregnancy, 13.0% at 3-12 months pre-pregnancy, 22.1% at <3 months pre-pregnancy and 13.4% during pregnancy. Compared with visits during pregnancy, RR of BV was 1.65 (95% CI: 1.00 to 2.71; p=0.05) at visits <3 months pre-pregnancy, 0.97 (95% CI: 0.62 to 1.52; p=0.90) at visits 3-12 months pre-pregnancy and 0.82 (95% CI: 0.44 to 1.53; p=0.53) at visits 12 months pre-pregnancy. An adjusted analysis including age, income, residence, date of first sex, recent sexual activity and positive sexually transmitted infection test resulted in small changes in risk estimates, with adjusted RR of BV of 1.66 (95% CI: 1.04 to 2.67; p=0.04) at visits <3 months pre-pregnancy compared with visits during pregnancy. CONCLUSIONS: BV risk during pregnancy was lower than during the immediate pre-pregnancy period. Hormonal changes in pregnancy may reduce BV.