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.

Assessing index CD4 and associated outcomes at 1-year in a tertiary HIV clinic, KwaZulu-Natal.

BACKGROUND:  Human immunodeficiency virus (HIV) management guidelines have evolved from initiating therapy at CD4 counts of ≤ 200 cells/m3 to implementing universal test and treat (UTT). This study aimed to assess whether in clinical practice, patients are presenting with higher baseline CD4 counts, describe the incidence of opportunistic infections and the proportion that achieved viral suppression. METHODS:  A retrospective cohort design with convenience sampling was conducted. Cohort 1 included patients initiated on antiretroviral therapy (ART) between 01 January 2014 and 31 December 2014, when criteria were set at CD4 count ≤ 350 cells/mm3. Cohort 2 included patients initiated on ART between 01 January 2019 and 31 December 2019, during the UTT era. RESULTS:  At ART initiation, the median CD4 cell was 170 cells/mm3 (interquartile range [IQR]: 85.5-287) in Cohort 1 cells/mm3 and 243 cells/mm3 (IQR: 120-411) in Cohort 2. Tuberculosis was the predominant OI in the group with CD4 cell count ≤ 200 cells/m3 in both Cohort 1 (26.8%) and Cohort 2 (27.9%), p = 0.039. At 1 year, virological suppression was achieved in only 77.7% and 84.7% of Cohorts 1 and 2 patients. CONCLUSION:  A notable portion of patients at King Edward VIII Hospital's HIV clinic commenced ART with CD4 counts significantly below the recommended guideline thresholds.Contribution: The research revealed a delay in initiating ART. A comprehensive reevaluation is essential to pinpoint the factors contributing to this delay and to devise customised interventions.

Risk factors for death in hospitalized COVID-19 patients in Africa: A systematic review and meta-analysis.

BACKGROUND: The coronavirus disease 2019 has quickly spread worldwide since it first appeared in Wuhan, China, in late 2019. The most affected country in Africa was South Africa. This study aimed to identify the risk factors for death in hospitalized COVID-19 patients in Africa. METHODS: We conducted a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. We searched articles from the following database: PubMed, Embase, Cochrane Library, Medline, and COVID-19 Research Database. We used Google Scholar for gray literature. The language used in this article was English. The last search was conducted on January 15, 2023. Pooled HRs, or ORs, and 95% confidence intervals, were calculated separately to identify the risk factors for death in hospitalized COVID-19 patients. Heterogeneity was assessed by Cochran's Q statistic and the I2 test. The Egger test was used to assess publication bias. Subgroup analysis was performed to determine the source of heterogeneity. Data analysis was performed using Stata version 17. A P value < .05 was considered significant. RESULTS: A total of 16,600 articles were obtained from the database search; finally, 16 articles met the inclusion criteria and were eligible for data extraction. The analysis revealed that the pooled prevalence of mortality in hospitalized COVID-19 patients was 13.9%. Advanced age was a significant risk factor for death in hospitalized COVID-19 patients, with the pooled coronavirus mortality HR and OR being 3.73 (95% CI: 2.27-5.19) and 1.04 (95% CI: 1.02-1.06), respectively. In addition, male gender (pOR 1.23; 95% CI: 1.07-1.40), patients with diabetes mellitus (DM) (pOR 1.26; 95% CI: 1.01-1.51), hypertension (HTN) (pOR 1.56; 95% CI: 1.27-1.85), chronic kidney disease (CKD) (pHR 5.43; 95% CI: 0.18-10.67), severe or critical conditions (pOR 9.04; 95% CI: 3.14-14.94) had a significantly increased risk of coronavirus-related mortality. The main limitations of the present study stem from the predominant use of published studies, which could introduce publication bias. CONCLUSION: According to this study, advanced age, male gender, hypertension, diabetes mellitus, chronic kidney disease, and severe or critical condition were clinical risk factors associated with death outcomes in hospitalized COVID-19 patients in Africa.

Protocol: Implementation evaluation of a combination intervention for sustainable blood pressure control in rural KwaZulu-Natal, South Africa (IMPACT BP): A three-arm, unblinded, parallel group individually randomized clinical trial.

BACKGROUND: Hypertension is the primary risk factor for stroke and heart disease, which are leading causes of death in South Africa. Despite the availability of treatments, there is an implementation gap in how best to deliver hypertension care in this resource-limited region. METHODS: We describe a three-arm parallel group individually randomized control trial to evaluate the effectiveness and implementation of a technology-supported, community-based intervention to improve blood pressure control among people with hypertension in rural KwaZulu-Natal. The study will compare three strategies: 1) standard of care (SOC arm) clinic-based management, 2) home-based blood pressure management supported by community blood pressure monitors (CBPM arm) and a mobile health application to record blood pressure readings and enable clinic-based nurses to remotely manage care, and 3) an identical strategy to the CBPM arm, except that participants will use a cellular blood pressure cuff, which automatically transmits completed readings over cellular networks directly to clinic-based nurses (eCBPM+ arm). The primary effectiveness outcome is change in blood pressure from enrollment to 6 months. The secondary effectiveness outcome is the proportion of participants with blood pressure control at 6 months. Acceptability, fidelity, sustainability, and cost-effectiveness of the interventions will also be assessed. CONCLUSIONS: In this protocol, we report the development of interventions in partnership with the South Africa Department of Health, a description of the technology-enhanced interventions, and details of the study design so that our intervention and evaluation can inform similar efforts in rural, resource-limited settings. PROTOCOL: Version 3 November 9th, 2022. CLINICALTRIALS: gov Trial Registration: NCT05492955 SAHPRA Trial Number: N20211201. SANCTR Number: DOH-27-112,022-4895.

Tuberculosis remains a major burden in systemic lupus erythematosus patients in Durban, South Africa.

Objective: Infections are common in systemic lupus erythematosus (SLE), with tuberculosis (TB) being important in an endemic environment. We studied the prevalence and spectrum of TB in SLE in Durban, South Africa. Methods: A medical records review of SLE patients seen over 13-year period, and the demographic data, clinical manifestations, laboratory findings, treatment and outcome were noted. Results: There were 512 SLE patients and 72 (14.1%) had TB. Thirty (41.7%) had pulmonary TB (PTB) and 42 (58.3%) had extra-pulmonary TB (EPTB). The prevalence of TB among the different ethnic groups was 36/282 (12.8%) for Indian people, 29/184 (15.8%) Black African people, 7/26 (26.9%) admixed African people and none among the 18 White people. Comparison of the 72 SLE-TB patients with 72 SLE controls showed no difference in gender, age at SLE diagnosis and disease duration. The SLE-TB patients had a significant increase in the clinical and laboratory features of disease activity (arthritis, mucocutaneous lesions, renal involvement, vasculitis, low complement, raised ds-DNA antibodies), and cumulative prednisone use over the preceding 3 months.Compared to PTB, the EPTB patients were significantly younger, developed TB earlier after SLE diagnosis, and had higher disease activity. The EPTB patients also had increase in features of disease activity (renal, thrombocytopenia, ds-DNA antibodies), and increase in ever use of intravenous methylprednisolone (IV-MP) and mycophenolate mofetil (MMF). On multivariate analysis, the independent risk factors for EPTB were ever use of MMF (p = 0.003) and IV-MP (p = 0.027). Analysis of the cumulative SLE criteria showed renal involvement was an independent risk factor for EPTB. The outcome was similar in both groups. Conclusion: We show an increased prevalence of TB (14.1%) and EPTB (58.3%) in SLE in an endemic area and confirm that features of disease activity and use of immunosuppressive therapy are the major risk factors. Renal involvement (as a cumulative criterion) is an independent risk factor for EPTB.

Antihistamines for motion sickness.

BACKGROUND: Motion sickness is a syndrome that occurs as a result of passive body movement in response to actual motion, or the illusion of motion when exposed to virtual and moving visual environments. The most common symptoms are nausea and vomiting. Antihistamines have been used in the management of motion sickness for decades, however studies have shown conflicting results regarding their efficacy. OBJECTIVES: To assess the effectiveness of antihistamines in the prevention and treatment of motion sickness in adults and children. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 7 December 2021. SELECTION CRITERIA: Randomised controlled trials (RCTs) in susceptible adults and children in whom motion sickness was induced under natural conditions such as air, sea and land transportation. We also included studies in which motion sickness was induced under experimental conditions (analysed separately). Antihistamines were included regardless of class, route or dosage and compared to no treatment, placebo or any other pharmacological or non-pharmacological interventions. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1) the proportion of susceptible participants who did not experience any motion sickness symptoms; 2) the proportion of susceptible participants who experienced a reduction or resolution of existing symptoms. Secondary outcomes were 1) physiological measures (heart rate, core temperature and gastric tachyarrhythmia (electrogastrography)) and 2) adverse effects (sedation, impaired cognition, blurred vision). We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included nine RCTs (658 participants). Studies were conducted across seven countries, with an overall age range of 16 to 55 years. Motion sickness was induced naturally in six studies and experimentally in four studies (rotating chair). All the naturally induced studies only evaluated first-generation antihistamines (cinnarizine and dimenhydrinate). Risk of bias across the studies varied, with mostly low risk for random sequence generation and allocation concealment, and mostly high risk for selective reporting. Only the experimentally induced studies measured physiological parameters and only the naturally induced studies evaluated adverse effects. There were no studies that clearly assessed the paediatric population. Antihistamines versus placebo or no treatment Antihistamines are probably more effective than placebo at preventing motion sickness symptoms under natural conditions (symptoms prevented: 25% placebo; 40% antihistamines) (risk ratio (RR) 1.81, 95% confidence interval (CI) 1.23 to 2.66; 3 studies; 240 participants) (moderate-certainty). The evidence is very uncertain about the effect of antihistamines on preventing motion sickness under experimental conditions (standardised mean difference (SMD) 0.32, 95% CI -0.18 to 0.83; 2 studies; 62 participants) (very low-certainty). No studies reported results on the resolution of existing motion sickness symptoms. Antihistamines may result in little or no difference in gastric tachyarrhythmia under experimental conditions (mean difference (MD) -2.2, 95% CI -11.71 to 7.31; 1 study; 42 participants) (low-certainty). No studies reported results for any other physiological measures. When compared to placebo, antihistamines may be more likely to cause sedation (sedation: 44% placebo; 66% antihistamines) (RR 1.51, 95% CI 1.12 to 2.02; 2 studies; 190 participants) (low-certainty); they may result in little or no difference in blurred vision (blurred vision: 12.5% placebo; 14% antihistamines) (RR 1.14, 95% CI 0.53 to 2.48; 2 studies; 190 participants) (low-certainty); and they may result in little or no difference in terms of impaired cognition (impaired cognition: 33% placebo; 29% antihistamines) (RR 0.89, 95% CI 0.58 to 1.38; 2 studies; 190 participants) (low-certainty). Antihistamines versus scopolamine The evidence is very uncertain about the effect of antihistamines on preventing motion sickness under natural conditions when compared to scopolamine (symptoms prevented: 81% scopolamine; 71% antihistamines) (RR 0.89, 95% CI 0.68 to 1.16; 2 studies; 71 participants) (very low-certainty). No studies were performed under experimental conditions. No studies reported results on the resolution of existing motion sickness symptoms. The evidence is very uncertain about the effect of antihistamines on heart rate under natural conditions (narrative report, 1 study; 20 participants; "No difference in pulse frequency"; very low-certainty). No studies reported results for any other physiological measures. When compared to scopolamine, the evidence is very uncertain about the effect of antihistamines on sedation (sedation: 21% scopolamine; 30% antihistamines) (RR 0.82, 95% CI 0.07 to 9.25; 2 studies; 90 participants) (very low-certainty) and on blurred vision (narrative report: not a significant difference; 1 study; 51 participants; very low-certainty). No studies evaluated impaired cognition. Antihistamines versus antiemetics Antihistamines may result in little or no difference in the prevention of motion sickness under experimental conditions (MD -0.20, 95% CI -10.91 to 10.51; 1 study; 42 participants) (low-certainty). The evidence is of low certainty due to imprecision as the sample size is small and the confidence interval crosses the line of no effect. No studies assessed the effects of antihistamines versus antiemetics under natural conditions. No studies reported results on the resolution of existing motion sickness symptoms. Antihistamines may result in little or no difference in gastric tachyarrhythmia (MD 4.56, 95% CI -3.49 to 12.61; 1 study; 42 participants) (low-certainty). No studies reported results for any other physiological measures. No studies evaluated sedation, impaired cognition or blurred vision. One study reported physiological data for this outcome, evaluating gastric tachyarrhythmia specifically. Antihistamines may result in little or no difference in gastric tachyarrhythmia (MD 4.56, 95% CI -3.49 to 12.61; 1 study; 42 participants; low-certainty evidence). This evidence is of low certainty due to imprecision as the sample size is small and the confidence interval crosses the line of no effect. Antihistamines versus acupuncture The evidence is very uncertain about the effects of antihistamines on the prevention of motion sickness under experimental conditions when compared to acupuncture (RR 1.32, 95% CI 1.12 to 1.57; 1 study; 100 participants) (very low-certainty). This study did not assess the prevention of motion sickness under natural conditions, nor the resolution of existing motion sickness symptoms. There was no study performed under natural conditions. Physiological measures and adverse effects were not reported. AUTHORS' CONCLUSIONS: There is probably a reduction in the risk of developing motion sickness symptoms under naturally occurring conditions of motion when using first-generation antihistamines, in motion sickness-susceptible adults, compared to placebo. Antihistamines may be more likely to cause sedation when compared to placebo. No studies evaluated the treatment of existing motion sickness, and there are few data on the effect of antihistamines in children. The evidence for all other outcomes and comparisons (versus scopolamine, antiemetics and acupuncture) was of low or very low certainty and we are therefore uncertain about these effects of antihistamines.

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.

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.

Omicron infection of vaccinated individuals enhances neutralizing immunity against the Delta variant.

Omicron variant (B.1.1.529) infections are rapidly expanding worldwide, often in settings where the Delta variant (B.1.617.2) was dominant. We investigated whether neutralizing immunity elicited by Omicron infection would also neutralize the Delta variant and the role of prior vaccination. We enrolled 23 South African participants infected with Omicron a median of 5 days post-symptoms onset (study baseline) with a last follow-up sample taken a median of 23 days post-symptoms onset. Ten participants were breakthrough cases vaccinated with Pfizer BNT162b2 or Johnson and Johnson Ad26.CoV2.S. In vaccinated participants, neutralization of Omicron increased from a geometric mean titer (GMT) FRNT50 of 28 to 378 (13.7-fold). Unvaccinated participants had similar Omicron neutralization at baseline but increased from 26 to only 113 (4.4-fold) at follow-up. Delta virus neutralization increased from 129 to 790, (6.1-fold) in vaccinated but only 18 to 46 (2.5-fold, not statistically significant) in unvaccinated participants. Therefore, in Omicron infected vaccinated individuals, Delta neutralization was 2.1-fold higher at follow-up relative to Omicron. In a separate group previously infected with Delta, neutralization of Delta was 22.5-fold higher than Omicron. Based on relative neutralization levels, Omicron re-infection would be expected to be more likely than Delta in Delta infected individuals, and in Omicron infected individuals who are vaccinated. This may give Omicron an advantage over Delta which may lead to decreasing Delta infections in regions with high infection frequencies and high vaccine coverage.

Immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Ad26.CoV2.S Vaccination in People Living With Human Immunodeficiency Virus (HIV).

BACKGROUND: People living with HIV (PLWH) have been reported to have a higher risk of more severe COVID-19 disease and death. We assessed the ability of the Ad26.CoV2.S vaccine to elicit neutralizing activity against the Delta variant in PLWH relative to HIV-negative individuals. We also examined effects of HIV status and suppression on Delta neutralization response in SARS-CoV-2-infected unvaccinated participants. METHODS: We enrolled participants who were vaccinated through the SISONKE South African clinical trial of the Ad26.CoV2.S vaccine in healthcare workers (HCWs). PLWH in this group had well-controlled HIV infection. We also enrolled unvaccinated participants previously infected with SARS-CoV-2. Neutralization capacity was assessed by a live virus neutralization assay of the Delta variant. RESULTS: Most Ad26.CoV2.S vaccinated HCWs were previously infected with SARS-CoV-2. In this group, Delta variant neutralization was 9-fold higher compared with the infected-only group and 26-fold higher relative to the vaccinated-only group. No decrease in Delta variant neutralization was observed in PLWH relative to HIV-negative participants. In contrast, SARS-CoV-2-infected, unvaccinated PLWH showed 7-fold lower neutralization and a higher frequency of nonresponders, with the highest frequency of nonresponders in people with HIV viremia. Vaccinated-only participants showed low neutralization capacity. CONCLUSIONS: The neutralization response of the Delta variant following Ad26.CoV2.S vaccination in PLWH with well-controlled HIV was not inferior to HIV-negative participants, irrespective of past SARS-CoV-2 infection. In SARS-CoV-2-infected and nonvaccinated participants, HIV infection reduced the neutralization response to SARS-CoV-2, with the strongest reduction in HIV viremic individuals.

Cause of hospitalization and death in the antiretroviral era in Sub-Saharan Africa published 2008-2018: A systematic review.

BACKGROUND: Worldwide despite the availability of antiretroviral therapy, human immunodeficiency virus/acquired immunodeficiency syndrome still causes morbidity and mortality among patients. In Sub-Saharan Africa, human immunodeficiency virus/acquired immunodeficiency syndrome remains a major public health concern. The aim of this study was to identify the causes of morbidity and mortality in the modern antiretroviral therapy era in Sub-Saharan Africa. METHODS: We conducted a systematic review according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We searched relevant studies from 3 databases which are Google Scholar, PubMed, and CINAHL. Two review authors independently screened titles, abstracts, and full-text articles in duplicate, extracted data, and assessed bias. Discrepancies were resolved by discussion or arbitration of a third review author. R software version 3.6.2 was used to analyze the data. Maximum values were used in order to show which disease was mostly spread out by looking at the highest prevalence reported. This systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO). RESULTS: A total of 409 articles were obtained from the database search, finally 12 articles met the inclusion criteria and were eligible for data extraction. Among them, 3 were conducted in Nigeria, 2 were conducted in Uganda, 3 were conducted in South Africa, 1 in Gabon, 1 in Ethiopia, 1 in Ghana, and 1 in Burkina Faso. In most of the included studies, tuberculosis was the leading cause of hospitalization which accounted for between 18% and 40.7% and it was also the leading cause of death and accounted for between 16% and 44.3%, except in 1 which reported anemia as the leading cause of hospitalization and in 2 which reported wasting syndrome and meningitis respectively as the leading causes of death. Opportunistic malignancies accounted between for 1.8% to 5% of hospitalization and 1.2% to 9.8% of deaths. CONCLUSIONS: Tuberculosis is the commonest cause of hospitalization and death in Sub-Saharan Africa, but it is always followed by other infectious disease and other non-AIDS related causes.

Treatment outcomes of Gene Xpert positive tuberculosis patients in KwaMashu Community Health Centre, KwaZulu-Natal, South Africa: A retrospective review.

BACKGROUND: We sought to investigate the relationship between tuberculosis (TB) treatment outcomes and its predictors in the KwaMashu region in KwaZulu-Natal (KZN). This area is currently a hotbed for TB and human immunodeficiency virus (HIV) co-infection. METHOD: A retrospective study design was adopted to characterise adult patients diagnosed with Gene Expert (GXP) positive pulmonary TB from 01 January 2016 to 31 December 2017. Tuberculosis treatment outcomes were assessed after two months and five months according to the standard World Health Organization (WHO) criteria. Multiple logistic regression analysis was used to calculate the odds ratio (OR) of the possible determinants associated with unsuccessful treatment outcomes. RESULTS: Amongst the 596 patients diagnosed, 57.4% (95% confidence interval [CI]: 53.3-61.4; 342 of 596) had successful treatment outcomes. Of these reported cases, 88.89% (85.1-92.0; 304 of 342) were cured. For the unsuccessful treatment outcomes, 52.4% (46.0-58.6; 133 of 254) patients were lost to follow-up, 20.9% (16.0-26.4; 53 of 254) failed treatment, 1.2% (0.2-3.4; 3 of 254) died and 25.6% (20.3-31.4; 65 of 254) of the patients could not be accounted for. Patients with unknown HIV status were more likely to have unsuccessful treatment outcomes (adjusted OR [aOR] = 4.94 [1.83-13.36]). Patients who had sputum conversion at 2 months (aOR = 1.94 [1.27-2.96]) were significantly more likely to exhibit unsuccessful treatment outcomes. CONCLUSION: Treatment success rate was 57.4% which was below the target set by the WHO. This underscores the urgent need to strengthen treatment adherence strategies to improve outcomes, especially in high HIV burden settings.

Risk factors for COVID-19-related in-hospital mortality in a high HIV and tuberculosis prevalence setting in South Africa: a cohort study.

BACKGROUND: The interaction between COVID-19, non-communicable diseases, and chronic infectious diseases such as HIV and tuberculosis is unclear, particularly in low-income and middle-income countries in Africa. South Africa has a national HIV prevalence of 19% among people aged 15-49 years and a tuberculosis prevalence of 0·7% in people of all ages. Using a nationally representative hospital surveillance system in South Africa, we aimed to investigate the factors associated with in-hospital mortality among patients with COVID-19. METHODS: In this cohort study, we used data submitted to DATCOV, a national active hospital surveillance system for COVID-19 hospital admissions, for patients admitted to hospital with laboratory-confirmed SARS-CoV-2 infection between March 5, 2020, and March 27, 2021. Age, sex, race or ethnicity, and comorbidities (hypertension, diabetes, chronic cardiac disease, chronic pulmonary disease and asthma, chronic renal disease, malignancy in the past 5 years, HIV, and past and current tuberculosis) were considered as risk factors for COVID-19-related in-hospital mortality. COVID-19 in-hospital mortality, the main outcome, was defined as a death related to COVID-19 that occurred during the hospital stay and excluded deaths that occurred because of other causes or after discharge from hospital; therefore, only patients with a known in-hospital outcome (died or discharged alive) were included. Chained equation multiple imputation was used to account for missing data and random-effects multivariable logistic regression models were used to assess the role of HIV status and underlying comorbidities on COVID-19 in-hospital mortality. FINDINGS: Among the 219 265 individuals admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and known in-hospital outcome data, 51 037 (23·3%) died. Most commonly observed comorbidities among individuals with available data were hypertension in 61 098 (37·4%) of 163 350, diabetes in 43 885 (27·4%) of 159 932, and HIV in 13 793 (9·1%) of 151 779. Tuberculosis was reported in 5282 (3·6%) of 146 381 individuals. Increasing age was the strongest predictor of COVID-19 in-hospital mortality. Other factors associated were HIV infection (adjusted odds ratio 1·34, 95% CI 1·27-1·43), past tuberculosis (1·26, 1·15-1·38), current tuberculosis (1·42, 1·22-1·64), and both past and current tuberculosis (1·48, 1·32-1·67) compared with never tuberculosis, as well as other described risk factors for COVID-19, such as male sex; non-White race; underlying hypertension, diabetes, chronic cardiac disease, chronic renal disease, and malignancy in the past 5 years; and treatment in the public health sector. After adjusting for other factors, people with HIV not on antiretroviral therapy (ART; adjusted odds ratio 1·45, 95% CI 1·22-1·72) were more likely to die in hospital than were people with HIV on ART. Among people with HIV, the prevalence of other comorbidities was 29·2% compared with 30·8% among HIV-uninfected individuals. Increasing number of comorbidities was associated with increased COVID-19 in-hospital mortality risk in both people with HIV and HIV-uninfected individuals. INTERPRETATION: Individuals identified as being at high risk of COVID-19 in-hospital mortality (older individuals and those with chronic comorbidities and people with HIV, particularly those not on ART) would benefit from COVID-19 prevention programmes such as vaccine prioritisation as well as early referral and treatment. FUNDING: South African National Government.

A trio of infectious diseases and pulmonary embolism: A developing world's reality.

INTRODUCTION: Human immunodeficiency virus (HIV), Tuberculosis (TB) and coronavirus disease (COVID-19) infections independently possess the ability to trigger formation of venous thromboembolism (VTE) and pulmonary embolism (PE). To the authors' knowledge, this is the first case report describing the presence of PE in a patient with all three aforementioned infectious co-morbidities. PRESENTATION: A patient living with HIV with virological failure secondary to defaulting antiretroviral therapy (ART) presented with hypoxia, clinical and radiological features suggestive of community-acquired pneumonia (CAP) with raised inflammatory markers and D-dimer levels. MANAGEMENT: She was commenced on prophylactic anticoagulation, supplemental oxygen and empirical antibiotics targeting CAP and pneumocystis jiroveci pneumonia, swabbed for COVID-19 infection and had sputa sent for Gene Xpert® TB testing. A day later, COVID-19 results returned positive and the patient was transferred to isolation and added onto dexamethasone and therapeutic anticoagulation. Sputa returned positive for mycobacterium TB a day later, and anti-tuberculosis therapy was added. She remained persistently hypoxic, with a Well's score of 3 placing her at moderate risk for PE, which prompted for a computed tomography pulmonary angiogram (CTPA) being ordered, which demonstrated left lower lobe subsegmental PE. Warfarin was added to her regimen. She was discharged on day 18 with a therapeutic international normalised ratio (INR) and not requiring oxygen therapy. CONCLUSION: This scenario is relevant in low to middle-income countries. The utilisation of a raised D-Dimer in the setting of all four coexisting conditions in arriving at a definite diagnosis remains uncertain. We noted that despite our index patient being on thrombo-prophylaxis, she developed PE highlighting the need for increased vigilance in all COVID-19 patients, even those on prophylactic anticoagulation.

Association of predicted 10 years cardiovascular mortality risk with duration of HIV infection and antiretroviral therapy among HIV-infected individuals in Durban, South Africa.

BACKGROUND: South Africa has the largest population of human immunodeficiency virus (HIV) infected patients on antiretroviral therapy (ART) realising the benefits of increased life expectancy. However, this population may be susceptible to cardiovascular disease (CVD) development, due to the chronic consequences of a lifestyle-related combination of risk factors, HIV infection and ART. We predicted a 10-year cardiovascular mortality risk in an HIV-infected population on long-term ART, based on their observed metabolic risk factor profile. METHODS: We extracted data from hospital medical charts for 384 randomly selected HIV-infected patients aged ≥ 30 years. We defined metabolic syndrome (MetS) subcomponents using the International Diabetes Federation definition. A validated non-laboratory-based model for predicting a 10-year CVD mortality risk was applied and categorised into five levels, with the thresholds ranging from very low-risk (< 5%) to very high-risk scores (> 30%). RESULTS: Among the 384 patients, with a mean (± standard deviation) age of 42.90 ± 8.20 years, the proportion of patients that were overweight/obese was 53.3%, where 50.9% had low high-density lipoprotein (HDL) cholesterol and 21 (17.5%) had metabolic syndrome. A total of 144 patients with complete data allowed a definitive prediction of a 10-year CVD mortality risk. 52% (95% CI 44-60) of the patients were stratified to very low risk (< 5%) compared to 8% (95% CI 4-13) that were at a very high risk (> 30%) of 10-year CVD mortality. The CVD risk grows with increasing age (years), 57.82 ± 6.27 among very high risk and 37.52 ± 4.50; p < 0.001 in very low risk patients. Adjusting for age and analysing CVD risk mortality as a continuous risk score, increasing duration of HIV infection (p = 0.002) and ART (p = 0.007) were significantly associated with increased predicted 10 year CVD mortality risk. However, there was no association between these factors and categorised CVD mortality risk as per recommended scoring thresholds. CONCLUSIONS: Approximately 1 in 10 HIV-infected patients is at very high risk of predicted 10-year CVD mortality in our study population. Like uninfected individuals, our study found increased age as a major predictor of 10-year mortality risk and high prevalence of metabolic syndrome. Additional CVD mortality risk due to the duration of HIV infection and ART was seen in our population, further studies in larger and more representative study samples are encouraged. It recommends an urgent need for early planning, prevention and management of metabolic risk factors in HIV populations, at the point of ART initiation.

Improvement in Muscular Strength in HIV-Infected Individuals Receiving Antiretroviral Therapy.

PURPOSE: This study investigated (1) the effect of a progressive resistance training (PRT) program and whey protein intake on maximal muscle strength in human immunodeficiency virus (HIV)-infected individuals receiving antiretroviral therapy (ART) and (2) alterations in maximal strength 12 wks after the cessation of PRT with continued supplementation. METHODS: Sixty HIV-infected individuals were recruited. Whole body PRT was performed twice weekly for 12 wks. Participants received, in a double-blind placebo controlled manner, either 20 g whey or placebo (maltodextrin) before and immediately after each session. Both PRT groups continued to take either whey protein or placebo for a further 12 wks following the exercise intervention to examine the effects of detraining. RESULTS: Forty participants (mean and standard deviation (SD) age 40.8 (±7.7) years, weight 70.8 (±16) kg, body mass index (BMI) 30.9 (±7.2) kg m2); whey protein /PRT (n = 13), placebo/PRT (n = 17), and a control group (n = 10) completed the study. A significant main effect for time occurred for the bench press (p = 0.02), the squat (p < 0.0001), the deadlift (p = 0.001) and the shoulder press (p = 0.02) one-repetition maximum (1RM) in the intervention groups. CONCLUSION: The PRT program increased maximal strength regardless of whey protein intake. The detraining period demonstrated minimal strength loss, which is beneficial to this population.

Risk factors and co-morbidities associated with changes in renal function among antiretroviral treatment-naïve adults in South Africa: A chart review.

INTRODUCTION: Our systematic scoping review has demonstrated a research gap in antiretroviral treatment (ART) nephrotoxicity as well as in the long-term outcomes of renal function for patients on ART in South Africa. Bearing in mind the high prevalence of human immunodeficiency virus (HIV) in South Africa, this is of great concern. OBJECTIVES: To determine the risk factors and co-morbidities associated with changes in renal function in HIV-infected adults in South Africa. METHODS: We conducted a retrospective study of 350 ART-naïve adult patients attending the King Edward VIII HIV clinic, Durban, South Africa. Data were collected at baseline (pre-ART) and at six, 12, 18 and 24 months on ART. Renal function was assessed in the 24-month period using the Modification of Diet in Renal Disease equation and was categorised into normal renal function (estimated glomerular filtration rate [eGFR] ≥ 60), moderate renal impairment (eGFR 30-59), severe renal impairment (eGFR 15-29) and kidney failure (eGFR < 15 mL/min/1.73 m2). Generalised linear models for binary data were used to model the probability of renal impairment over the five time periods, controlling for repeated measures within participants over time. Risk ratios and 95% confidence intervals (CI) were reported for each time point versus baseline. RESULTS: The cohort was 64% female, and 99% were Black. The median age was 36 years. At baseline, 10 patients had hypertension (HPT), six had diabetes, 61 were co-infected with tuberculosis (TB) and 157 patients had a high body mass index (BMI) with 25.4% being categorised as overweight and 19.4% as obese. The majority of the patients (59.3%) were normotensive. At baseline, the majority of the patients (90.4%) had normal renal function (95% CI: 86% - 93%), 7.0% (CI: 5% - 10%) had moderate renal impairment, 1.3% (CI: 0% - 3%) had severe renal impairment and 1.3% (CI: 0% - 3%) had renal failure. As BMI increased by one unit, the risk of renal impairment increased by 1.06 (CI: 1.03-1.10) times. The association of HPT with abnormal renal function was found to be insignificant, p > 0.05. The vast majority of patients were initiated on tenofovir disoproxil fumarate (TDF) (90.6%), in combination with lamivudine (3TC) (100%) and either efavirenz (EFV) (56.6%) or nevirapine (NVP) (43.4%). CONCLUSION: This study reports a low prevalence of baseline renal impairment in HIV-infected ART-naïve outpatients. An improvement in renal function after the commencement of ART has been demonstrated in this population. However, the long-term outcomes of patients with HIV-related renal disease are not known.

Serum procalcitonin levels predict acute kidney injury in critically ill patients.

AIM: To determine whether admission procalcitonin (PCT) was associated with the subsequent development of acute kidney injury (AKI) in a general population of critically ill patients. METHODS: The study was a retrospective observational study conducted in a multidisciplinary intensive care unit (ICU) over a period of 1 year. Adult patients who had a PCT performed on admission and who did not have chronic kidney disease (CKD) or AKI on admission, were evaluated for the development of AKI within the first week of ICU admission, according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The association between PCT on admission and the development of AKI was explored for the entire cohort and for septic and non-septic subgroups. RESULTS: Two hundred and one patients were included in the study. The incidence of AKI in the first 7 days of ICU admission was 36.8%. PCT, age, the presence of shock on admission, and sepsis were significantly associated with AKI on univariate analysis. Multivariable analysis of the entire cohort revealed that age, shock and sepsis remained independent predictors of AKI, while PCT was no longer significant. When the septic and non-septic patients were analyzed separately a PCT ≥10 ng/mL remained the only significant predictor of AKI in the non-septic patients (OR 4.430; 95% CI 1.464-13.399), but was not an independent predictor of AKI in septic patients. CONCLUSION: The main finding of this study was the significant association of an elevated PCT on admission with the development of AKI in the non-septic patient. An elevated PCT in a non-septic patient identifies a patient at increased risk of AKI. PCT requires further study as a novel biomarker of AKI in non-septic patients.

Incidence of chemotherapy-induced neutropenia in HIV-infected and uninfected patients with breast cancer receiving neoadjuvant chemotherapy.

BACKGROUND: Chemotherapy-induced neutropenia (CIN) can result in poor tolerance of chemotherapy, leading to dose reductions, delays in therapy schedules, morbidity and mortality. Actively identifying predisposing risk factors before treatment is of paramount importance. We hypothesised that chemotherapy is associated with a greater increase in CIN and its complications in HIV-infected patients than in those who are not infected. OBJECTIVE: To establish the incidence of CIN in HIV-infected and uninfected patients undergoing chemotherapy. METHODS: A retrospective chart review and analysis was conducted in the oncology departments at Inkosi Albert Luthuli Central Hospital and Addington Hospital, Durban, South Africa. The study population consisted of 65 previously untreated women of all ages with stage II - IV breast cancer and known HIV status treated with neoadjuvant chemotherapy from January 2012 to December 2015. RESULTS: HIV-infected patients formed 32.3% of the group, and 95.2% of them were on antiretroviral therapy. The mean age (standard deviation (SD)) of the cohort was 48.5 (13.2) years (40.6 (9.6) years for the HIV-infected group v. 52.0 (13.1) years for the uninfected group; p<0.001). Ninety-five neutropenia episodes were observed (rate 0.85 per 1 year of follow-up time). Following multivariate adjustment, patients with HIV infection were almost two times more likely to develop CIN (hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.06 - 2.92; p=0.029. A high baseline absolute neutrophil count (ANC) (HR 0.80, 95% CI 0.68 - 0.95; p=0.005) remained significantly associated with protection against CIN. CONCLUSIONS: HIV-infected patients were younger than those who were not infected, and presented at a more locally advanced stage of disease. HIV infection was an independent predictor for CIN. HIV-infected patients had an almost two-fold increased risk of developing CIN and developed neutropenia at a much faster rate. A high baseline white cell count and ANC were protective against CIN.