Omicron infection enhances Delta antibody immunity in vaccinated persons.

The extent to which Omicron infection1-9, with or without previous vaccination, elicits protection against the previously dominant Delta (B.1.617.2) variant is unclear. Here we measured the neutralization capacity against variants of severe acute respiratory syndrome coronavirus 2 in 39 individuals in South Africa infected with the Omicron sublineage BA.1 starting at a median of 6 (interquartile range 3-9) days post symptom onset and continuing until last follow-up sample available, a median of 23 (interquartile range 19-27) days post symptoms to allow BA.1-elicited neutralizing immunity time to develop. Fifteen participants were vaccinated with Pfizer's BNT162b2 or Johnson & Johnson's Ad26.CoV2.S and had BA.1 breakthrough infections, and 24 were unvaccinated. BA.1 neutralization increased from a geometric mean 50% focus reduction neutralization test titre of 42 at enrolment to 575 at the last follow-up time point (13.6-fold) in vaccinated participants and from 46 to 272 (6.0-fold) in unvaccinated participants. Delta virus neutralization also increased, from 192 to 1,091 (5.7-fold) in vaccinated participants and from 28 to 91 (3.0-fold) in unvaccinated participants. At the last time point, unvaccinated individuals infected with BA.1 had low absolute levels of neutralization for the non-BA.1 viruses and 2.2-fold lower BA.1 neutralization, 12.0-fold lower Delta neutralization, 9.6-fold lower Beta variant neutralization, 17.9-fold lower ancestral virus neutralization and 4.8-fold lower Omicron sublineage BA.2 neutralization relative to vaccinated individuals infected with BA.1. These results indicate that hybrid immunity formed by vaccination and Omicron BA.1 infection should be protective against Delta and other variants. By contrast, infection with Omicron BA.1 alone offers limited cross-protection despite moderate enhancement.

Higher plasma interleukin - 6 levels are associated with lung cavitation in drug-resistant tuberculosis.

BACKGROUND: Lung cavitation is associated with heightened TB transmission and poor treatment outcomes. This study aimed to determine the relationship between systemic inflammation and lung cavitation in drug-resistant TB patients with and without HIV co-infection. METHODS: Plasma samples were obtained from 128 participants from the CAPRISA 020 Individualized M(X)drug-resistant TB Treatment Strategy Study (InDEX) prior to treatment initiation. Lung cavitation was present in 61 of the 128 drug-resistant TB patients with 93 being co-infected with HIV. The plasma cytokine and chemokine levels were measured using the 27-Plex Human Cytokine immunoassay. Modified Poisson regression models were used to determine the association between plasma cytokine/chemokine expression and lung cavitation in individuals with drug-resistant TB. RESULTS: Higher Interleukin-6 plasma levels (adjusted risk ratio [aRR] 1.405, 95% confidence interval [CI] 1.079-1.829, p = 0.011) were associated with a higher risk of lung cavitation in the multivariable model adjusting for age, sex, body mass index, HIV status, smoking and previous history of TB. Smoking was associated with an increased risk of lung cavitation (aRR 1.784, 95% CI 1.167-2.729, p = 0.008). An HIV positive status and a higher body mass index, were associated with reduced risk of lung cavitation (aRR 0.537, 95% CI 0.371-0.775, p = 0.001 and aRR 0.927, 95% CI 0.874-0.983, p = 0.012 respectively). CONCLUSION: High plasma interleukin-6 levels are associated with an increased risk of cavitary TB highlighting the role of interleukin-6 in the immunopathology of drug-resistant TB.

Blood monocyte and dendritic cell profiles among people living with HIV with Mycobacterium tuberculosis co-infection.

BACKGROUND: Understanding the complex interactions of the immune response mediated by Mycobacterium tuberculosis and HIV co-infection is fundamental to disease biomarker discovery, vaccine, and drug development. Using flow cytometry, we characterized the frequencies and phenotypic differences in monocytes and dendritic cell populations using peripheral blood mononuclear cells from individuals with recurrent, active pulmonary tuberculosis with and without coexisting HIV infection (CAPRISA 011, Clinicaltrials.gov, NCT02114684, 29/01/2014) and compared them to samples from HIV positive individuals and healthy controls. Additionally, we assessed the associations between the frequency of monocyte and dendritic cell subsets and time to culture conversion and cavitary disease in patients with active TB using a cox proportional hazards and logistic regression models. RESULTS: Compared to healthy controls, the frequency of total monocytes (HLA-DR + CD14 +) was significantly higher in the TB/HIV and TB groups and the frequency of dendritic cells (HLA-DR + CD14-) was significantly higher in TB/HIV and HIV groups. We observed significant variation in the expression of CCR2, CD40, CD11b, CD86, CD163, CX3CR1 across different cell subsets in the four study groups. Increase in CCR2, CD11b and CD40 was associated with active TB infection, while decrease in CX3CR1 and increase in CD163 was associated with HIV infection. Expression of CX3CR1 (aHR 0.98, 95% CI 0.963 - 0.997, p = 0.019) on non-classical monocytes associated with longer time to TB culture conversion in the multivariable model correcting for randomization arm, age, sex, HIV status, lung cavitation, alcohol use, smoking and BMI. Higher surface expression of CD86 (aOR 1.017, 95% CI 1.001 - 1.032, p = 0.033) on intermediate monocytes associated with the presence of lung cavitation, while higher expression of transitional monocytes (aOR 0.944, 95% CI 0.892 - 0.999, p = 0.047) associated with the absence of lung cavitation in the multivariable model. CONCLUSION: These data provide valuable insight into the heterogenous role of monocyte and dendritic cells in TB and HIV infections.

The V2 loop of HIV gp120 delivers costimulatory signals to CD4+ T cells through Integrin α4ß7 and promotes cellular activation and infection.

Acute HIV infection is characterized by rapid viral seeding of immunologic inductive sites in the gut followed by the severe depletion of gut CD4+ T cells. Trafficking of α4ß7-expressing lymphocytes to the gut is mediated by MAdCAM, the natural ligand of α4ß7 that is expressed on gut endothelial cells. MAdCAM signaling through α4ß7 costimulates CD4+ T cells and promotes HIV replication. Similar to MAdCAM, the V2 domain of the gp120 HIV envelope protein binds to α4ß7 In this study, we report that gp120 V2 shares with MAdCAM the capacity to signal through α4ß7 resulting in CD4+ T cell activation and proliferation. As with MAdCAM-mediated costimulation, cellular activation induced by gp120 V2 is inhibited by anti-α4ß7 monoclonal antibodies (mAbs). It is also inhibited by anti-V2 domain antibodies including nonneutralizing mAbs that recognize an epitope in V2 that has been linked to reduced risk of acquisition in the RV144 vaccine trial. The capacity of the V2 domain of gp120 to mediate signaling through α4ß7 likely impacts early events in HIV infection. The capacity of nonneutralizing V2 antibodies to block this activity reveals a previously unrecognized mechanism whereby such antibodies might impact HIV transmission and pathogenesis.

Clinical Evaluation of Severe Acute Respiratory Syndrome Coronavirus 2 Rapid Antigen Tests During the Omicron Wave in South Africa.

We evaluated the performance of nasal and nasopharyngeal Standard Q COVID-19 [coronavirus disease 2019] Ag tests (SD Biosensor) and the Panbio COVID-19 Ag Rapid Test Device (nasal; Abbott) against the Abbott RealTime severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assay during the Omicron (clades 21M, 21K, and 21L) wave in South Africa. Overall, all evaluated tests performed well, with high sensitivity (range, 77.78%-81.42%) and excellent specificity values (>99%). The sensitivity of rapid antigen tests increased above 90% in samples with cycle threshold <20, and all 3 tests performed best within the first week after symptom onset.

Genital Immune Cell Activation and Tenofovir Gel Efficacy: A Case-Control Study.

Genital inflammation (GI) undermines topical human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) efficacy through unknown mechanisms. Here, associations between activated endocervical CD4 + T-cell numbers and higher deoxyadenosine triphosphate (dATP) concentrations suggest that competition for intracellular metabolites within HIV target cells may reduce the efficacy of antiretroviral-based PrEP in women with GI.

Preferential Infection of α4ß7+ Memory CD4+ T Cells During Early Acute Human Immunodeficiency Virus Type 1 Infection.

BACKGROUND: Establishment of persistent human immunodeficiency virus type 1 (HIV-1) reservoirs occurs early in infection, and biomarkers of infected CD4+ T cells during acute infection are poorly defined. CD4+ T cells expressing the gut homing integrin complex α4ß7 are associated with HIV-1 acquisition, and are rapidly depleted from the periphery and gastrointestinal mucosa during acute HIV-1 infection. METHODS: Integrated HIV-1 DNA was quantified in peripheral blood mononuclear cells obtained from acutely (Fiebig I-III) and chronically infected individuals by sorting memory CD4+ T-cell subsets lacking or expressing high levels of integrin ß7 (ß7negative and ß7high, respectively). HIV-1 DNA was also assessed after 8 months of combination antiretroviral therapy (cART) initiated in Fiebig II/III individuals. Activation marker and chemokine receptor expression was determined for ß7-defined subsets at acute infection and in uninfected controls. RESULTS: In Fiebig I, memory CD4+ T cells harboring integrated HIV-1 DNA were rare in both ß7high and ß7negative subsets, with no significant difference in HIV-1 DNA copies. In Fiebig stages II/III and in chronically infected individuals, ß7high cells were enriched in integrated and total HIV-1 DNA compared to ß7negative cells. During suppressive cART, integrated HIV-1 DNA copies decreased in both ß7negative and ß7high subsets, which did not differ in DNA copies. In Fiebig II/III, integrated HIV-1 DNA in ß7high cells was correlated with their activation. CONCLUSIONS: ß7high memory CD4+ T cells are preferential targets during early HIV-1 infection, which may be due to the increased activation of these cells.

Plasma Cytokine Predictors of Tuberculosis Recurrence in Antiretroviral-Treated Human Immunodeficiency Virus-infected Individuals from Durban, South Africa.

BACKGROUND: Immune correlates of tuberculosis (TB) risk in populations infected with human immunodeficiency virus (HIV) remain understudied, despite HIV being associated with a high burden of TB disease. Here we describe plasma cytokine correlates of TB recurrence in a well-characterized cohort of HIV-infected individuals on antiretroviral therapy (ART) with a history of prior TB cure. METHODS: Study participants were drawn from a prospective cohort study initiated at the conclusion of a randomized clinical trial in which individuals presented with untreated HIV infection and active pulmonary TB. At baseline, ART was initiated, and TB successfully cured. Participants were screened for TB recurrence quarterly for up to 4 years. TB recurrent cases (n = 63) were matched to controls (n = 123) on sex, study arm assignment in the original trial, and month of enrollment with a subset of cases sampled longitudinally at several time-points. RESULTS: Three cytokines were associated with increased rates of TB recurrence in univariate models: interleukin 6 (IL6) (odds ratio [OR] 2.66, 95% confidence interval [CI] 1.34-5.28, P = .005), IP10 (OR 4.62, 95% CI 1.69-12.65, P = .003), monokine induced by IFN-γ (MIG) (OR 3.11, 95% CI 1.10-8.82, P = .034). Conversely, interferon ß (IFNß) was associated with decreased TB risk (OR 0.34, 95% CI 0.13-0.87, P = .025). Following multivariate analyses adjusting for covariates IL6, interleukin 1ß (IL1ß), and interleukin 1Rα (IL1Rα) were associated with increased risk and IFNß with decreased TB risk. Longitudinal analysis showed that levels of many TB-associated markers, including IL6, IP10, sCD14, and interferon γ (IFNγ) are reduced following TB treatment. CONCLUSION: These data show that TB recurrence, in HIV-infected individuals on ART is predicted by biomarkers of systemic inflammation, many of which are implicated in more rapid HIV disease progression. CLINICAL TRIALS REGISTRATION: NCT 01539005.

Circulating immunoglobulins and transient lymphocytopenia in a sub-study of CAPRISA 012B, testing HIV monoclonal antibodies in a phase 1 trial.

Acute, transient lymphocytopenia, not clinically significant was observed in the CAPRISA 012B phase 1 clinical trial following administration of broadly neutralizing antibodies (bnAb)-CAP256V2LS alone or with VRC07-523LS. Lymphocytopenia was assigned upon a > 50% decline in absolute lymphocyte counts following bnAb administration. We posited that systemic immunoglobulins (Igs), and cytokine profiles of eight women who developed lymphocytopenia were different to the 12 women without lymphocytopenia. Plasma Ig subclasses (IgG)/isotypes (IgM/IgA), and 27 cytokines were measured at enrolment (prior to bnAbs) and at days 1, 7, 28, 56 post-bnAb administration. IgG subclasses, IgM and total lymphocyte counts were significantly lower prior to bnAbs in women with gradable lymphocytopenia than those without. Gradable lymphocytopenia compared to non-lymphocytopenia women had significantly higher MIP-1ß from enrolment up to day 56. TNF-α was significantly lower in gradable lymphocytopenia compared to non-lymphocytopenia women for enrolment, days 7, 28 and 56 except for day 1. Within the gradable and within the non-lymphocytopenia women, from enrolment to day 1, significantly elevated IL-6, IL-8, IP-10, MCP-1, G-CSF and IL-1RA were found. Additionally, within the gradable lymphocytopenia women, 9 additional cytokines (TNF-α, MIP-1α, MIP-1ß, RANTES, Basic FGF, eotaxin, IFN-γ, IL-17A and IL-4) were significantly elevated at day 1 post-bnAbs compared to enrolment. This sub study presents preliminary findings to support the monitoring of baseline immunological markers including lymphocyte counts for assessing the development of transient lymphocytopenia. In high-risk settings conducting clinical trials testing bnAbs for HIV prevention, understanding factors that could amplify rates of lymphocytopenia, even if transient, remain undefined.

Epigenetic control of IRF1 responses in HIV-exposed seronegative versus HIV-susceptible individuals.

Not all individuals exposed to HIV become infected. Understanding why these HIV-exposed seronegative individuals remain uninfected will help inform the development of preventative measures against HIV infection. Interferon regulatory factor-1 (IRF1) plays a critical role both in host antiviral immunity and in HIV-1 replication. This study examined IRF1 expression regulation in the ex vivo peripheral blood mononuclear cells of HIV-exposed seronegative commercial sex workers who can be epidemiologically defined as relatively resistant to HIV infection (HIV-R), versus HIV-uninfected, susceptible controls (HIV-S). Whereas HIV-susceptible individuals demonstrated a biphasic, prolonged increase in IRF1 expression after interferon-γ stimulation, HIV-R individuals demonstrated a robust, but transient response. We also found that the IRF1 promoter in HIV-R was primed by increased basal histone deacetylase-2 binding, independently of transcription regulators, STAT1 and nuclear factor-κB/p65, implicating an epigenetic silencing mechanism. Interestingly, the transitory IRF1 response in HIV-R was sufficient in comparable regulation of interleukin-12 and interleukin-4 expression compared with the HIV-susceptible controls. This is the first study characterizing IRF1 responsiveness in individuals who demonstrate altered susceptibility to HIV infection. These data suggest that transitory IRF1 responsiveness in HIV-R may be one of the key contributors to the altered susceptibility to HIV infection during the early stages of primary HIV infection.

Age and menopause affect the expression of specific cytokines/chemokines in plasma and cervical lavage samples from female sex workers in Nairobi, Kenya.

BACKGROUND: Aging of the immune system, known as immunosenescence, is associated with profound changes in both innate and adaptive immune responses, resulting in increased susceptibility to infection and a decreased ability to respond to vaccination. The purpose of this study was to investigate the effect of age and menopause on the expression of 22 different cytokines/chemokines in both plasma and cervical lavage samples from female sex-worker cohort from Nairobi, Kenya (age range 20-65). RESULTS: Cytokine/chemokine levels were measured using a Miliplex multiplex assay (Millipore). We found that age positively correlated with MCP-1 (p = 0.0002) and IP-10 (p = 0.03) systemic cytokine expression, and that women over 50 expressed the highest levels of these cytokines, but also had elevated expression of MIG (ANOVA p = 0.0096) and MIP-3ß(ANOVA p = 0.0434). We also found that IL-8 (p = 0.047) and sCD40L (p = 0.01) systemic expression negatively correlated with age. Further, MIG (p = 0.0081) and MCP-1 (p = 0.0157) were present at higher levels in post-menopausal women suggesting a potential estrogen dependant systemic regulation of these cytokines. In cervical lavage samples, age did not directly correlate with the expression of any of the tested cytokines/chemokines, however sIL-2Rα (ANOVA p = 0.0170) and IL-15 (ANOVA p = 0.0251)were significantly higher in women over 50. Menopause was shown to have a more profound effect on cytokine expression in the cervical mucosa with MIG (p = 0.0256), MIP-3α (p = 0.0245), IL-1ß (p = 0.0261), IL-6 (p = 0.0462), IL-8 (p = 0.007), IP-10 (p = 0.0357) and MCP-1 (p = 0.0427) all significantly under-expressed in post-menopausal women. CONCLUSIONS: This study demonstrates that aging and menopause-associated hormonal changes are associated with significant changes in systemic and mucosal cytokine/chemokine expression, which may have implications for the age-related decline in the ability to fight against infections.

The Performance of Diagnostic Tests for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the South African Population: A Scoping Review.

To determine the performance and reliability of diagnostic tests for the identification of SARS-CoV-2 infection in South Africa, we conducted a scoping review to identify published studies undertaken in the English language from March 2020 to August 2022 that evaluated the performance of antigen- and antibody-based diagnostic tests for SARS-CoV-2 in South Africa. We identified 17 relevant peer-reviewed articles; six reported on SARS-CoV-2 gene and/or antigen detection whilst 11 reported on antibody detection. Of the SARS-CoV-2 gene and/or antigen-based tests, sensitivity ranged from 40% to 100%, whilst for the antibody-based tests, sensitivity ranged from 13% to 100%. All tests evaluated were highly dependent on the stage of infection and the timing of sample collection. This scoping review demonstrated that no single SARS-CoV-2 gene and/or antigen- or antibody-based assay was sufficiently sensitive and specific simultaneously. The sensitivity of the tests was highly dependent on the timing of sample collection with respect to SARS-CoV-2 infection. In the case of SARS-CoV-2 gene and/or antigen detection, the earlier the collection of samples, the greater the sensitivity, while antibody detection tests showed better sensitivity using samples from later stages of infection.

NK cell phenotypic profile during active TB in people living with HIV-evolution during TB treatment and implications for bacterial clearance and disease severity.

Natural killer (NK) cells, key effector cells of the innate immune system, play an important role in the clearance and control of Mycobacterium tuberculosis and HIV infections. Here, we utilized peripheral blood specimens from the Improving Retreatment Success CAPRISA 011 study to characterize NK cell phenotypes during active TB in individuals with or without HIV co-infection. We further assessed the effects of TB treatment on NK cell phenotype, and characterized the effects of NK cell phenotypes during active TB on mycobacterial clearance and TB disease severity measured by the presence of lung cavitation. TB/HIV co-infection led to the expansion of functionally impaired CD56neg NK cell subset. TB treatment completion resulted in restoration of total NK cells, NK cell subset redistribution and downregulation of several NK cell activating and inhibitory receptors. Higher percentage of peripheral CD56bright cells was associated with longer time to culture conversion, while higher expression of NKp46 on CD56dim NK cells was associated with lower odds of lung cavitation in the overall cohort and the TB/HIV co-infected participants. Together these results provide a detailed description of peripheral NK cells in TB and TB/HIV co-infection and yield insights into their role in TB disease pathology.

Single-nucleotide polymorphisms in ABC drug transporters alter expression and circulating tenofovir in healthy South African women exposed to pre-exposure prophylaxis.

Aim: We investigated if single-nucleotide polymorphisms (SNPs) in ATP-binding cassette (ABC) drug transporters alter gene expression and tenofovir disposition in South African women taking Truvada® for HIV prevention. Materials & methods: In 393 women, real-time PCR was used to determine the associations between six SNPs in ABC transporter genes, mRNA expression and circulating-tenofovir. Results: Univariable and multivariable analyses showed that CT and TT relative to CC genotypes for the ABCC4(3463C/T) SNP had significantly higher tenofovir levels. In contrast, the AA genotype for the ABCC4(4976A/G) SNP showed significantly less tenofovir, while mRNA expression was increased. Conclusion: SNPs in the ABCC4 gene may differentially affect gene expression and circulating tenofovir. Their impact may inform on low pre-exposure prophylaxis efficacy and discern effective drugs in clinical trials of African women enriched for certain genotypes.

Drug-Resistant TB, HIV and COVID-19 Co-Infection: Case Reviews from Kwa-Zulu Natal, South Africa.

Background: Coronavirus disease (COVID-19) potentially exacerbates drug-resistant tuberculosis (DR-TB). We describe the clinical presentation and outcomes of three patients with human immunodeficiency virus (HIV), DR-TB and COVID-19. Case One: A virologically suppressed 31-year-old man on antiretroviral therapy (ART) and multidrug-resistant (MDR)-TB treatment presented with mild COVID-19 and was hospitalised for 10 days of clinical monitoring, despite being clinically stable with normal baseline inflammatory markers. Severe acute respiratory syndrome coronavirus polymerase chain reaction (SARS-CoV-2 PCR) positivity persisted at Day 28. Case Two: A virologically suppressed 37-year-old woman on ART and MDR-TB treatment presented with moderate COVID-19. Baseline inflammatory markers were raised, and dexamethasone and azithromycin were initiated with good clinical improvement. SARS-CoV-2 PCR positivity persisted at Day 28. Case Three: A viraemic 24-year-old woman on second-line ART and MDR-TB treatment, presented with mild COVID-19 disease, normal oxygenation and normal inflammatory markers, and remained clinically stable with negative SARS-CoV-2 PCR at Days 14 and 28. Conclusion: Screening for SARS-CoV-2 infection is advised for DR-TB patients with new or worsening respiratory symptoms.

Field evaluations of four SARS-CoV-2 rapid antigen tests during SARS-CoV-2 Delta variant wave in South Africa.

BACKGROUND: Rapid antigen tests detecting SARS-CoV-2 were shown to be a useful tool in managing the COVID-19 pandemic. Here, we report on the results of a prospective diagnostic accuracy study of four SARS-CoV-2 rapid antigen tests in a South African setting. METHODS: Rapid antigen test evaluations were performed through drive-through testing centres in Durban, South Africa, from July to December 2021. Two evaluation studies were performed: nasal Panbio COVID-19 Ag Rapid Test Device (Abbott) was evaluated in parallel with the nasopharyngeal Espline SARS-CoV-2 Ag test (Fujirebio), followed by the evaluation of nasal RightSign COVID-19 Antigen Rapid test Cassette (Hangzhou Biotest Biotech) in parallel with the nasopharyngeal STANDARD Q COVID-19 Ag test (SD Biosensor). The Abbott RealTime SARS-CoV-2 assay was used as a reference test. RESULTS: Evaluation of Panbio and Espline Ag tests was performed on 494 samples (31% positivity), while the evaluation of Standard Q and RightTest Ag tests was performed on 539 samples (13.17% positivity). The overall sensitivity for all four tests ranged between 60 and 72% with excellent specificity values (> 98%). Sensitivity increased to > 80% in all tests in samples with cycle number value < 20. All four tests performed best in samples from patients presenting within the first week of symptom onset. CONCLUSIONS: All four evaluated tests detected a majority of the cases within the first week of symptom onset with high viral load.

High prevalence of vaccine-preventable anal human papillomavirus infections is associated with HIV infection among gay, bisexual, and men who have sex with men in Nairobi, Kenya.

BACKGROUND: Human papillomavirus (HPV) infection is associated with anal cancers and is more prevalent in gay, bisexual, and men who have sex with men (gbMSM), partly due to their vulnerability to HIV infection. Baseline HPV genotype distributions and risk factors can inform the design of next-generation HPV vaccines to prevent anal cancer. METHODS: A cross-sectional study was conducted among gbMSM receiving care at a HIV/STI clinic in Nairobi, Kenya. Anal swabs were genotyped using a Luminex microsphere array. Multiple logistic regression methods were used to identify risk factors for four HPV outcomes (any HPV, any HR-HPV, and 4- and 9-valent vaccine-preventable HPVs). RESULTS: Among 115 gbMSM, 51 (44.3%) were HIV-infected. Overall HPV prevalence was 51.3%; 84.3% among gbMSM living with HIV and 24.6% among gbMSM without HIV (p < 0.001). One-third (32.2%) had HR-HPV and the most prevalent vaccine-preventable HR-HPV genotypes were 16, 35, 45, and 58. HPV-18 was uncommon (n = 2). The 9-valent Gardasil vaccine would have prevented 61.0% of HPV types observed in this population. In multivariate analyses, HIV status was the only significant risk factor for any HPV (adjusted odds ratio [aOR]:23.0, 95% confidence interval [95% CI]: 7.3-86.0, p < 0.001) and for HR-HPV (aOR: 8.9, 95% CI: 2.8-36.0, p < 0.001). Similar findings were obtained for vaccine-preventable HPVs. Being married to a woman significantly increased the odds of having HR-HPV infections (aOR: 8.1, 95% CI: 1.6-52.0, p = 0.016). CONCLUSIONS: GbMSM living with HIV in Kenya are at higher risk of anal HPV infections including genotypes that are preventable with available vaccines. Our findings support the need for a targeted HPV vaccination campaign in this population.

Metronidazole Treatment Failure and Persistent BV Lead to Increased Frequencies of Activated T- and Dendritic-Cell Subsets.

Metronidazole (MDZ) treatment failure and bacterial vaginosis (BV) recurrence rates are high among African women. This cohort study identified genital immune parameters associated with treatment response by comparing vaginal microbiota and immune cell frequencies in endocervical cytobrushes obtained from 32 South African women with symptomatic BV pre- and post-metronidazole treatment. Cervical T- and dendritic-cell subsets were phenotyped using multiparameter flow cytometry and the composition of vaginal microbial communities was characterized using 16S rRNA gene sequencing. MDZ treatment led to a modest decrease in the relative abundance of BV-associated bacteria, but colonization with Lactobacillus species (other than L. iners) was rare. At 6 and 12 weeks, MDZ-treated women had a significant increase in the frequencies of CCR5+ CD4+ T cells and plasmacytoid dendritic cells compared to the pre-treatment timepoint. In addition, MDZ non-responders had significantly higher frequencies of activated CD4 T cells and monocytes compared to MDZ responders. We conclude that MDZ treatment failure was characterized by an increased expression of activated T- and dendritic-cell subsets that may enhance HIV susceptibility. These data suggest the need to further assess the long-term impact of MDZ treatment on mucosal immune response and the vaginal microbiota.

Performance of rapid antigen tests in identifying Omicron BA.4 and BA.5 infections in South Africa.

BACKGROUND: Concerns around accuracy and performance of rapid antigen tests continue to be raised with the emergence of new SARS-CoV-2 variants. OBJECTIVE: To evaluate the performance of two widely used SARS-CoV-2 rapid antigen tests during BA.4/BA.5 SARS-CoV-2 wave in South Africa (May - June 2022). STUDY DESIGN: A prospective field evaluation compared the SARS-CoV-2 Antigen Rapid test from Hangzhou AllTest Biotech (nasal swab) and the Standard Q COVID-19 Rapid Antigen test from SD Biosensor (nasopharyngeal swab) to the Abbott RealTime SARS-CoV-2 assay (nasopharyngeal swab) on samples collected from 540 study participants. RESULTS: Overall 28.52% (154/540) were SARS-CoV-2 RT-PCR positive with median cycle number value of 12.30 (IQR 9.30-19.40). Out of the 99 successfully sequenced SARS-CoV-2 positive samples, 18 were classified as BA.4 and 56 were classified as BA.5. The overall sensitivities of the AllTest SARS-CoV-2 Ag test and Standard Q COVID-19 Ag test were 73.38% (95% CI 65.89-79.73) and 74.03% (95% CI 66.58-80.31) and their specificities were 97.41% (95% CI 95.30-98.59) and 99.22% (95% CI 97.74-99.74) respectively. Sensitivity was >90% when the cycle number value was <20. The sensitivity of both rapid tests was >90% in samples infected with Omicron sub-lineage BA.4 and BA.5. CONCLUSION: Accuracy of tested rapid antigen tests that target the nucleocapsid SARS-CoV-2 protein, were not adversely affected by BA.4 and BA.5 Omicron sub-variants.