Subclinical tuberculosis linkage to care and completion of treatment following community-based screening in rural South Africa.

Background: Tuberculosis (TB), a leading cause of infectious death, is curable when patients complete a course of multi-drug treatment. Because entry into the TB treatment cascade usually relies on symptomatic individuals seeking care, little is known about linkage to care and completion of treatment in people with subclinical TB identified through community-based screening. Methods: Participants of the Vukuzazi study, a community-based survey that provided TB screening in the rural uMkhanyakude district of KwaZulu-Natal from May 2018 - March 2020, who had a positive sputum (GeneXpert or Mtb culture, microbiologically-confirmed TB) or a chest x-ray consistent with active TB (radiologically-suggested TB) were referred to the public health system. Telephonic follow-up surveys were conducted from May 2021 - January 2023 to assess linkage to care and treatment status. Linked electronic TB register data was accessed. We analyzed the effect of baseline HIV and symptom status (by WHO 4-symptom screen) on the TB treatment cascade. Results: Seventy percent (122/174) of people with microbiologically-confirmed TB completed the telephonic survey. In this group, 84% (103/122) were asymptomatic and 46% (56/122) were people living with HIV (PLWH). By self-report, 98% (119/122) attended a healthcare facility after screening, 94% (115/122) started TB treatment and 93% (113/122) completed treatment. Analysis of electronic TB register data confirmed that 67% (116/174) of eligible individuals started TB treatment. Neither symptom status nor HIV status affected linkage to care. Among people with radiologically-suggested TB, 48% (153/318) completed the telephonic survey, of which 80% (122/153) were asymptomatic and 52% (79/153) were PLWH. By self-report, 75% (114/153) attended a healthcare facility after screening, 16% (24/153) started TB treatment and 14% (22/153) completed treatment. Nine percent (28/318) of eligible individuals had TB register data confirming that they started treatment. Conclusions: Despite high rates of subclinical TB, most people diagnosed with microbiologically-confirmed TB after community-based screening were willing to link to care and complete TB treatment. Lower rates of linkage to care in people with radiologically-suggested TB highlight the importance of streamlined care pathways for this group. Clearer guidelines for the management of people who screen positive during community-based TB screening are needed. Supplementary Information: The online version contains supplementary material available at 10.1186/s44263-024-00059-0.

Population Effectiveness of Dolutegravir Implementation in Uganda - A Prospective Observational Cohort Study (DISCO): 48-week Results.

BACKGROUND: Tenofovir/lamivudine/dolutegravir (TLD) is the preferred first-line antiretroviral therapy (ART) regimen for people with HIV (PWH), including those who were previously virologically suppressed on non-nucleoside reverse transcriptase inhibitors (NNRTIs). We sought to estimate the real-world effectiveness of the TLD transition in Ugandan public-sector clinics. METHODS: We conducted a prospective cohort study of PWH ≥18 years who were transitioned from NNRTI-based ART to TLD. Study visits were conducted on the day of TLD transition and 24- and 48- weeks later. The primary endpoint was viral suppression (<200 copies/mL) at 48-weeks. We collected blood for retrospective viral load (VL) assessment and conducted genotypic resistance tests for specimens with VL >500 copies/mL. RESULTS: We enrolled 500 participants (median age of 47 years; 41% women). At 48-weeks after TLD transition, 94% of participants were in care with a VL <200 copies/mL (n = 469/500); 2% (n = 11/500) were lost from care or died; and only 2% (n = 9/500) had a VL >500 copies/mL. No incident resistance to DTG was identified. Few participants (2%, n = 9/500) discontinued TLD due to adverse events. CONCLUSIONS: High rates of viral suppression, high tolerability, and lack of emergent drug resistance support use of TLD as the preferred first-line regimen in the region.

Southern African HIV Clinicians Society Guideline for the clinical management of syphilis.

Syphilis, 'the great imitator', caused by Treponema pallidum infection, remains a complex and multifaceted disease with a rich history of clinical diversity. This guideline aims to be a comprehensive guide for healthcare workers in Southern Africa, offering practical insights into the epidemiology, pathogenesis, clinical manifestations, diagnostic testing, therapeutic principles, and public health responses to syphilis. Although the syphilis burden has declined over the years, recent data indicate a troubling resurgence, particularly among pregnant women and neonates. This guideline highlights the diagnostic challenges posed by syphilis, stemming from the absence of a single high-sensitivity and -specificity test. While treatment with penicillin remains the cornerstone of treatment, alternative regimens may be used for specific scenarios. We highlight the importance of thorough patient follow-up and management of sex partners to ensure optimal care of syphilis cases. In the context of public health, we emphasise the need for concerted efforts to combat the increasing burden of syphilis, especially within high-risk populations, including people living with HIV.

Regional variation in weight change after the transition to dolutegravir: a prospective cohort study in Uganda and South Africa.

BACKGROUND: People with HIV (PWH) on integrase inhibitor-based regimens may be at risk of excess weight gain, but it is unclear if this risk is consistent across settings. We assessed weight change over 48 weeks among PWH who were transitioned to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD). DESIGN: We conducted a prospective cohort study at public-sector HIV clinics in Uganda and South Africa. METHODS: Eligible participants were adults who were transitioned to TLD. Weight was measured at enrollment, 24-, and 48-weeks post TLD transition. Our outcomes were (1) weight change, (2) change in waist circumference, and (3) clinically significant weight gain, defined as ≥10% increase in weight from baseline, over 48 weeks. We used linear mixed-effects regression models, adjusted for demographic factors, to estimate weight gain and identify risk factors. RESULTS: Weight data were available for 428 participants in Uganda and 367 in South Africa. The mean weight change was 0.6 kg [95%CI: 0.1-1.0] in Uganda and 2.9 kg [2.3-3.4] in South Africa (p < 0.001). The mean change in waist circumference was 0.8 cm [95%CI: 0.0-1.5]) in Uganda and 2.3 cm [95%CI: 1.4-3.2] in South Africa (p = 0.012). Clinically significant weight gain occurred in 9.8% [7.0-12.6] of participants in Uganda and 18.0% [14.1-21.9] in South Africa (p < 0.001). After adjustment, PWH gained significantly less weight in Uganda than in South Africa. CONCLUSIONS: PWH in South Africa experienced significantly greater weight gain and increases in waist circumference compared to Uganda. Strategies to address weight gain in PWH should be carefully considered and may vary by region.

Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation.

SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort of SARS-CoV-2 infected people in South Africa (n = 994) including participants with advanced HIV disease characterized by immunosuppression due to T cell depletion. Fifty-four percent of participants with advanced HIV disease had prolonged SARS-CoV-2 infection (>1 month). In the five vaccinated participants with advanced HIV disease tested, SARS-CoV-2 clearance associates with emergence of neutralizing antibodies but not SARS-CoV-2 specific CD8 T cells, while CD4 T cell responses were not determined due to low cell numbers. Further, complete HIV suppression is not required for clearance, although it is necessary for an effective vaccine response. Persistent SARS-CoV-2 infection led to SARS-CoV-2 evolution, including virus with extensive neutralization escape in a Delta variant infected participant. The results provide evidence that neutralizing antibodies are required for SARS-CoV-2 clearance in HIV-mediated immunosuppression recovery, and that suppressive ART is necessary to curtail evolution of co-infecting pathogens to reduce individual health consequences as well as public health risk linked with generation of escape mutants.

SARS-CoV-2 infection in immunosuppression evolves sub-lineages which independently accumulate neutralization escape mutations.

One mechanism of variant formation may be evolution during long-term infection in immunosuppressed people. To understand the viral phenotypes evolved during such infection, we tested SARS-CoV-2 viruses evolved from an ancestral B.1 lineage infection lasting over 190 days post-diagnosis in an advanced HIV disease immunosuppressed individual. Sequence and phylogenetic analysis showed two evolving sub-lineages, with the second sub-lineage replacing the first sub-lineage in a seeming evolutionary sweep. Each sub-lineage independently evolved escape from neutralizing antibodies. The most evolved virus for the first sub-lineage (isolated day 34) and the second sub-lineage (isolated day 190) showed similar escape from ancestral SARS-CoV-2 and Delta-variant infection elicited neutralizing immunity despite having no spike mutations in common relative to the B.1 lineage. The day 190 isolate also evolved higher cell-cell fusion and faster viral replication and caused more cell death relative to virus isolated soon after diagnosis, though cell death was similar to day 34 first sub-lineage virus. These data show that SARS-CoV-2 strains in prolonged infection in a single individual can follow independent evolutionary trajectories which lead to neutralization escape and other changes in viral properties.

Evolution and neutralization escape of the SARS-CoV-2 BA.2.86 subvariant.

Omicron BA.2.86 subvariant differs from Omicron BA.2 as well as recently circulating variants by over 30 mutations in the spike protein alone. Here we report on the isolation of the live BA.2.86 subvariant from a diagnostic swab collected in South Africa which we tested for escape from neutralizing antibodies and viral replication properties in cell culture. We found that BA.2.86 does not have significantly more escape relative to Omicron XBB.1.5 from neutralizing immunity elicited by either Omicron XBB-family subvariant infection or from residual neutralizing immunity of recently collected sera from the South African population. BA.2.86 does have extensive escape relative to ancestral virus with the D614G substitution (B.1 lineage) when neutralized by sera from pre-Omicron vaccinated individuals and relative to Omicron BA.1 when neutralized by sera from Omicron BA.1 infected individuals. BA.2.86 and XBB.1.5 show similar viral infection dynamics in the VeroE6-TMPRSS2 and H1299-ACE2 cell lines. We also investigate the relationship of BA.2.86 to BA.2 sequences. The closest BA.2 sequences are BA.2 samples from Southern Africa circulating in early 2022. Similarly, many basal BA.2.86 sequences were sampled in Southern Africa. This suggests that BA.2.86 potentially evolved in this region, and that unobserved evolution led to escape from neutralizing antibodies similar in scale to recently circulating strains of SARS-CoV-2.

Determinants of health-related quality of life in people with Human Immunodeficiency Virus, failing first-line treatment in Africa.

BACKGROUND: Antiretroviral treatment improves health related quality of life (HRQoL) of people with human immunodeficiency virus (PWH). However, one third initiating first-line treatment experience virological failure and the determinants of HRQoL in this key population are unknown. Our study aims to identify determinants of among PWH failing antiretroviral treatment in sub-Saharan Africa. METHODS: We analysed data from a cohort of PWH having virological failure (> 1,000 copies/mL) on first-line ART in South Africa and Uganda. We measured HRQoL using the EuroQOL EQ-5D-3L and used a two-part regression model to obtain by-country analyses for South Africa and Uganda. The first part identifies risk factors that were associated with the likelihood of participants reporting perfect health (utility = 1) versus non-perfect health (utility < 1). The second part identifies risk factors that were associated with the EQ-5 L-3L utility scores for participants reporting non-perfect health. We performed sensitivity analyses to compare the results between the two-part model using tobit models and ordinary least squares regression. RESULTS: In both countries, males were more likely to report perfect health and participants with at least one comorbidity were less likely to report perfect health. In South Africa, participants with side effects and in Uganda those with opportunistic infections were also less likely to report perfect health. In Uganda, participants with 100% ART adherence were more likely to report perfect health. In South Africa, high HIV viral load, experiencing ART side effects, and the presence of opportunistic infections were each associated with lower HRQoL, whereas participants with 100% ART adherence reported higher HRQoL. In Uganda participants with lower CD4 count had lower HRQoL. CONCLUSION: Markers of advanced disease (opportunistic infection, high viral load, low CD4), side effects, comorbidities and lack of ART adherence negatively impacted HRQoL for PWH experiencing virological failure. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02787499.

Hen egg white bovine colostrum supplement reduces symptoms of mild/moderate COVID-19: a randomized control trial.

Aim: The ability of a hen egg white bovine colostrum supplement to prevent severe COVID-19 was tested in a double-blind randomized control study. Methods: Adults with mild/moderate COVID-19, risk factors for severe disease, and within 5 days of symptom onset were assigned to the intervention (n = 77) or placebo (n = 79) arms. Symptoms were documented until day 42 post-enrollment and viral clearance was assessed at 11-13 days post-symptom onset. Results: One participant developed severe COVID-19. The severe-type symptom score was lower in the active arm at 11-13 days post-symptom onset (p = 0.049). Chest pain, fever/chills, joint pain/malaise, and sore throat were significantly less frequent in the active arm. No differences in viral clearance were observed. Conclusion: The intervention reduced symptoms of mild/moderate COVID-19. Clinical Trial Registration: DOH-27-062021-9191 (South African National Clinical Trials Register).

Natural proteins found in milk (lactoferrin) and egg white (ovotransferrin and lysozyme) could have therapeutic value in COVID-19 through their effects on the immune system. We identified bovine colostrum and hen egg white powders containing adequate quantities of these proteins. We investigated whether short-term daily consumption of a hen egg white and bovine colostrum mixture (reconstituted with glycerin and water) could reduce the risk of progression to severe disease and assist in the recovery of patients with mild or moderate COVID-19. Adults with mild or moderate COVID-19 who were within 5 days of symptom onset and had risk factors for severe disease were enrolled, and randomly assigned to take a hen egg white and bovine colostrum mixture or placebo mixture twice daily for 5 days, and then followed up telephonically for 6 weeks. The main findings were that consumption of the hen egg white and bovine colostrum mixture was associated with fewer protocol-defined severe-type symptoms overall, and in particular lower frequencies of joint pain/malaise, chest pain, fever/chills, and sore throat. Only one individual developed severe COVID-19 and therefore the effect of the intervention on reducing the risk of progression to severe disease could not be assessed. The results of this study suggest that consumption of the hen egg white bovine colostrum mixture within a few days of symptom onset lessens symptoms in people with mild or moderate COVID-19.

Food Insecurity Is Associated With Low Tenofovir Diphosphate in Dried Blood Spots in South African Persons With HIV.

Background: Food insecurity has been linked to suboptimal antiretroviral therapy (ART) adherence in persons with HIV (PWH). This association has not been evaluated using tenofovir diphosphate (TFV-DP) in dried blood spots (DBSs), a biomarker of cumulative ART adherence and exposure. Methods: Within a prospective South African cohort of treatment-naive PWH initiating ART, a subset of participants with measured TFV-DP in DBS values was assessed for food insecurity status. Bivariate and multivariate median-based regression analysis compared the association between food insecurity and TFV-DP concentrations in DBSs adjusting for age, sex, ethnicity, medication possession ratio (MPR), and estimated glomerular filtration rate. Results: Drug concentrations were available for 285 study participants. Overall, 62 (22%) PWH reported worrying about food insecurity and 44 (15%) reported not having enough food to eat in the last month. The crude median concentrations of TFV-DP in DBSs differed significantly between those who expressed food insecurity worry versus those who did not (599 [interquartile range {IQR}, 417-783] fmol/punch vs 716 [IQR, 453-957] fmol/punch; P = .032). In adjusted median-based regression, those with food insecurity worry had concentrations of TFV-DP that were 155 (95% confidence interval, -275 to -35; P = .012) fmol/punch lower than those who did not report food insecurity worry. Age and MPR remained significantly associated with TFV-DP. Conclusions: In this study, food insecurity worry is associated with lower TFV-DP concentrations in South African PWH. This highlights the role of food insecurity as a social determinant of HIV outcomes including ART failure and resistance.

Symbolic and anticipated HIV stigma are associated with mental health and education in South Africa.

HIV stigma continues to act as a barrier to HIV care in South Africa, necessitating further research on the intersections of socioeconomic factors and the anticipation and expression of stigma surrounding HIV. We measured the prevalence of HIV-related stigma and evaluated factors associated with symbolic and anticipated stigma in Umlazi Township, South Africa from 2013 to 2019, using a validated HIV stigma scale, before undergoing HIV testing. Among 7,724 people evaluated, 1,318 (16.9%) reported symbolic stigma and 2,396 (30.8%) anticipated HIV stigma. Prevalence of symbolic and anticipated stigma were significantly more common among both women and people living with HIV, compared to men and those who tested negative for HIV. In multivariable analyses, higher education and depressive symptoms were the strongest correlates with both symbolic stigma and anticipated stigma. Younger age, not being married, and having a partner who was not living with HIV appeared to be important correlates with anticipated stigma, but not symbolic stigma. Overall, the anticipation of experiencing stigma because of infection with HIV continues to be an important factor in the testing and management of HIV.

Seemingly Unrelated Regression Analysis of the Cost and Health-Related Quality of Life Outcomes of the REVAMP Randomized Clinical Trial.

OBJECTIVE: This study aimed to evaluate the 9-month cost and health-related quality of life (HRQOL) outcomes of resistance versus viral load testing strategies to manage virological failure in low-middle income countries. METHODS: We analyzed secondary outcomes from the REVAMP clinical trial: a pragmatic, open label, parallel-arm randomized trial investigating resistance versus viral load testing for individuals failing first-line treatment in South Africa and Uganda. We collected resource data, valued according to local cost data and used the 3-level version of EQ-5D to measure HRQOL at baseline and 9 months. We applied seemingly unrelated regression equations to account for the correlation between cost and HRQOL. We conducted intention-to-treat analyses with multiple imputation using chained equations for missing data and performed sensitivity analyses using complete cases. RESULTS: For South Africa, resistance testing and opportunistic infections were associated with statistically significantly higher total costs, and virological suppression was associated with lower total cost. Higher baseline utility, higher cluster of differentiation 4 (CD4) count, and virological suppression were associated with better HRQOL. For Uganda, resistance testing and switching to second-line treatment were associated with higher total cost, and higher CD4 was associated with lower total cost. Higher baseline utility, higher CD4 count, and virological suppression were associated with better HRQOL. Sensitivity analyses of the complete-case analysis confirmed the overall results. CONCLUSION: Resistance testing showed no cost or HRQOL advantage in South Africa or Uganda over the 9-month REVAMP clinical trial.

Point-of-care urine tenofovir testing to predict HIV drug resistance among individuals with virologic failure.

OBJECTIVE: We sought to evaluate the utility of a point-of-care (POC) urine tenofovir (TFV) assay, developed to objectively assess adherence, to predict HIV drug resistance (HIVDR) in people failing first-line antiretroviral therapy (ART). DESIGN: We retrospectively analyzed TFV levels as a biomarker of adherence in urine specimens collected during a clinical trial that enrolled adults with virologic failure on first-line ART in Uganda and South Africa. METHODS: Urine specimens were analyzed from participants on TFV-containing regimens who had a viral load >1000 copies/ml and paired genotypic resistance test (GRT) results. We assessed recent ART TFV adherence with a qualitative POC lateral flow urine assay with a cut-off value of 1500 ng/ml. We then calculated performance characteristics of the POC urine TFV assay to predict HIVDR, defined as intermediate or high-level resistance to any component of the current ART regimen. RESULTS: Urine specimens with paired plasma GRT results were available from 283 participants. The most common ART regimen during study conduct was emtricitabine, tenofovir disoproxil fumarate, and efavirenz. The overall prevalence of HIVDR was 86% ( n = 243/283). Of those with TFV detected on the POC assay, 91% ( n  = 204/224) had HIVDR, vs. only 66% ( n  = 39/59) among those with no TFV detected ( P- value < 0.001). Positive and negative predictive values of the assay to predict HIVDR were 91% and 34%, respectively. CONCLUSIONS: In populations with a high prevalence of HIVDR, the POC urine TFV assay can provide a low-cost, rapid method to guide requirements for confirmatory resistance testing and inform the need for regimen change.

SARS-CoV-2 evolves increased infection elicited cell death and fusion in an immunosuppressed individual.

The milder clinical manifestations of Omicron infection relative to pre-Omicron SARS CoV-2 raises the possibility that extensive evolution results in reduced pathogenicity. To test this hypothesis, we quantified induction of cell fusion and cell death in SARS CoV-2 evolved from ancestral virus during long-term infection. Both cell fusion and death were reduced in Omicron BA.1 infection relative to ancestral virus. Evolved virus was isolated at different times during a 6-month infection in an immunosuppressed individual with advanced HIV disease. The virus isolated 16 days post-reported symptom onset induced fusogenicity and cell death at levels similar to BA.1. However, fusogenicity was increased in virus isolated at 6 months post-symptoms to levels intermediate between BA.1 and ancestral SARS-CoV-2. Similarly, infected cell death showed a graded increase from earlier to later isolates. These results may indicate that, at least by the cellular measures used here, evolution in long-term infection does not necessarily attenuate the virus.

A comprehensive overview of pneumococcal vaccination recommendations for adults in South Africa, 2022.

Pneumococcal infections remain a common global cause of significant morbidity and mortality. The first recommendations for adult pneumococcal vaccination, published in South Africa in 1999, contained information only on the 23-valent polysaccharide vaccine (PPV23). With the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) for use in adults and the perceived uncertainty that most clinicians had regarding use of these vaccines in adults, these vaccine recommendations were updated in 2022. A Working Group, which consisted of individuals in various fields of medical practice in South Africa, who were from different areas of the country, and included clinicians from both the public and private sectors, was assembled to revise the recommendations. The expertise of the participants varied widely, dependent on their training and specialty, and encompassed different organ systems, disease conditions, and/or practice types. Each participant was allocated a different section, based on their expertise, for which they were required to do an extensive review of the current literature and write their section. The entire working group then reviewed the complete document several times, following additional comments and recommendations. This update contains recommendations for the use of both PPV23 and PCV13, either alone, or in sequence, both in vaccine naïve and in previously vaccinated individuals. It includes both age and risk categories, and encompasses the elderly (≥65 years), as well as younger adults (<65 years) with comorbid conditions or with high-risk conditions and/or immunocompromise. It is hoped that this review and its associated vaccine recommendations will clarify for clinicians, from all spheres of practice in South Africa, how, where, and when pneumococcal vaccines should be used in adults, with the ultimate goal of significantly increasing the appropriate use of these vaccines, in order to decrease the substantial morbidity and mortality associated with pneumococcal infections in adults in South Africa. Furthermore, it is hoped that this review of local epidemiological data and the manner in which this information was interpreted in the development of these local vaccine recommendations, could be used as an example for other regions of the world, to tailor their recommendations to locally available epidemiological data.

Prognostic variables and 4-year survival outcomes in CD20 Positive AIDS-Related Lymphoma in the Anti-retroviral treatment era: A Retrospective Review from a Single Centre in KwaZulu-Natal, South Africa.

OBJECTIVE: To describe 4-year survival outcomes and assess the value of established and additional relevant variables to predict complete response (CR), four-year progression-free survival (PFS) and overall survival (OS) of CD20 positive AIDS-Related Lymphoma (ARL) treated with standard combination chemotherapy. METHOD: We performed a retrospective review of patients diagnosed with CD20 positive ARL between 2006 and 2016. All patients over 12 years of age who received at least one cycle of combination chemotherapy with curative intent were included in the analysis. Variables assessed included the International Prognostic Index (IPI), age-adjusted-IPI, age, gender, B symptoms, extent of disease, functional performance status, CD4 cell count, viral load, concurrent ART with chemotherapy, rituximab inclusion, and number of chemotherapy cycles used. Kaplan-Meier survival curves for OS and PFS at 4 years were compared for IPI and aaIPI using the log-rank test. A Cox proportional hazards model was used to investigate the effects of prognostic variables for patients achieving OS and PFS at 4 years and logistic regression for patients achieving CR. RESULTS: A total of 102 patients were included in the analysis. At year four of follow-up, the OS was 50% (n = 51) and PFS was 43% (n = 44). Attaining a CR and male gender were significantly associated with improved 4-year OS (p<0.001 and p = 0.028 respectively) and PFS (p<0.001 and 0.048 respectively). A viral load of < 50 copies/ml was associated with a higher complete response rate (aOR 6.10 [95% CI 1.15, 24.04], p = 0.01). Six or more cycles of chemotherapy was superior to fewer cycles for both PFS (aHR 0.17 [95% CI 0.10, 0.29]) and OS (aHR 0.12 [95% CI 0.07, 0.22]) with p-value < 0.001 for both PFS and OS. The Kaplan-Meier survival estimates demonstrated the prognostic utility of the IPI and aaIP for OS (p = 0.002 and 0.030 respectively) and the IPI for PFS (p = 0.002). CONCLUSION: This study is a first from a high prevalence HIV area in KwaZulu-Natal, South Africa, and confirms the utility of the internationally accepted prognostic scoring systems in predicting survival in CD20 positive ARL in the local population.

Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection.

SARS-CoV-2 Omicron (B.1.1.529) BA.4 and BA.5 sub-lineages, first detected in South Africa, have changes relative to Omicron BA.1 including substitutions in the spike receptor binding domain. Here we isolated live BA.4 and BA.5 viruses and measured BA.4/BA.5 neutralization elicited by BA.1 infection either in the absence or presence of previous vaccination as well as from vaccination without BA.1 infection. In BA.1-infected unvaccinated individuals, neutralization relative to BA.1 declines 7.6-fold for BA.4 and 7.5-fold for BA.5. In vaccinated individuals with subsequent BA.1 infection, neutralization relative to BA.1 decreases 3.2-fold for BA.4 and 2.6-fold for BA.5. The fold-drop versus ancestral virus neutralization in this group is 4.0-fold for BA.1, 12.9-fold for BA.4, and 10.3-fold for BA.5. In contrast, BA.4/BA.5 escape is similar to BA.1 in the absence of BA.1 elicited immunity: fold-drop relative to ancestral virus neutralization is 19.8-fold for BA.1, 19.6-fold for BA.4, and 20.9-fold for BA.5. These results show considerable escape of BA.4/BA.5 from BA.1 elicited immunity which is moderated with vaccination and may indicate that BA.4/BA.5 may have the strongest selective advantage in evading neutralization relative to BA.1 in unvaccinated, BA.1 infected individuals.

Patient characteristics and outcome of CD20-positive HIV-associated lymphoma: a single-center KwaZulu-Natal, South African hospital 12-year retrospective review.

BACKGROUND: Due to the high prevalence of HIV, HIV-associated lymphoma (HAL) is a common malignancy in South Africa. However, there is a paucity of literature on HAL from this region. The objective of this study was to profile the clinical characteristics and outcome of CD20-positive HAL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), with or without rituximab (R), from a single center in KwaZulu -Natal, South Africa. METHODS: Retrospective chart review of adult patients treated from 2006 to 2018 for HIV-associated CD20-positive lymphoma. The clinical characteristics, complete response (CR), and 2-year overall survival (OS) are described. RESULTS: The analysis included 102 patients, 54% females, median age of 39 years, and median CD4 cell count of 196 cells/µL. Bone marrow involvement was noted in 5%. Eighty-six percent of the cohort received concomitant antiretroviral therapy and chemotherapy, 76% of the CHOP group, and 92% of the R-CHOP group. Overall, a CR was seen in 55% (95% CI 45%; 65%), with a 2-year OS of 59% (95% CI 50%, 69%). A CR was attained in 46% on CHOP and 64% on R-CHOP, with a 2-year disease-free survival (DFS) for CHOP of 42% and 50% for R-CHOP. CONCLUSION: Although the clinical characteristics and laboratory findings are similar to other higher-income cohorts, there was a difference in gender and incidence of marrow involvement. The low incidence of marrow involvement has prompted more routine use of immunohistochemistry and flow cytometry in staging marrows of HAL locally. Further randomized studies are required for the establishment of locally validated, cost-effective treatment guidelines.