Critical illness due to infection in people living with HIV.

People living with HIV comprise a substantial number of the patients admitted to intensive care. This number varies according to geography, but all areas of the world are affected. In lower-income and middle-income countries, the majority of intensive care unit (ICU) admissions relate to infections, whereas in high-income countries, they often involve HIV-associated non-communicable diseases diagnoses. Management of infections potentially resulting in admission to the ICU in people living with HIV include sepsis, respiratory infections, COVID-19, cytomegalovirus infection, and CNS infections, both opportunistic and non-opportunistic. It is crucial to know which antiretroviral therapy (ART) is appropriate, when is the correct time to administer it, and to be aware of any safety concerns and potential drug interactions with ART. Although ART is necessary for controlling HIV infections, it can also cause difficulties relevant to the ICU such as immune reconstitution inflammatory syndrome, and issues associated with ART administration in patients with gastrointestinal dysfunction on mechanical ventilation. Managing infection in people with HIV in the ICU is complex, requiring collaboration from a multidisciplinary team knowledgeable in both the management of the specific infection and the use of ART. This team should include intensivists, infectious disease specialists, pharmacists, and microbiologists to ensure optimal outcomes for patients.

The influence of smoking and HIV infection on pulmonary function.

Background: Prevalence of HIV, smoking, and pulmonary infections in South Africa are high. Objectives: We investigated the role of smoking and HIV status on lung function. Methods: This is a secondary analysis of a cross-sectional study conducted in South Africa. Data included demographics, pulmonary risk factors and a spirometry test to obtain the forced expiratory volume in one second (FEV1) and the ratio of FEV1/forced vital capacity (FVC). In the initial multivariable regression analysis, the effect of smoking on pulmonary function in HIV-positive adults was assessed. The analysis was repeated, assessing the influence of HIV status on lung function in both HIV-negative and HIV-positive smokers. The models were adjusted for age, sex, body mass index (BMI), time since HIV diagnosis, antiretroviral treatment (ART) use, occupational hazards, history of tuberculosis or pneumonia, indoor smoking and the presence of an indoor fireplace during childhood. Results: This study included 524 people living with HIV (PLWH, 66.7% female, mean age 40.9 years [s.d.; 9.4]) and 79 HIV-negative smokers (77.2% male, mean age 34.4 years [s.d.: 12.1]). Of the PLWH, 118 (22.5%) were past or current smokers and 406 (77.5%) were non-smokers. Smoking was not associated with changes in the FEV1 or FEV1/FVC ratio in multivariable regression analysis. In the second analysis, HIV status was also not associated with reduced pulmonary function following adjustment for confounders. Conclusion: Neither smoking nor being HIV-positive was associated with decreased pulmonary function in this relatively young population. These findings should be confirmed in a longitudinal study, including an older population.

Corrigendum: The influence of HIV infection and antiretroviral treatment on pulmonary function in individuals in an urban setting in sub-Saharan Africa.

[This corrects the article DOI: 10.4102/sajhivmed.v22i1.1312.].

Erratum: Unexpected low frequency of respiratory symptoms in an HIV-positive urban sub-Saharan population compared to an HIV-negative control group.

[This corrects the article DOI: 10.4102/sajhivmed.v20i1.1010.].

Comparison of outcomes in HIV-positive and HIV-negative patients with COVID-19.

BACKGROUND: South Africa has the highest prevalence of HIV in the world and to date has recorded the highest number of cases of COVID-19 in Africa. There is uncertainty as to what the significance of this dual infection is, and whether people living with HIV (PLWH) have worse outcomes compared to HIV-negative patients with COVID-19. This study compared the outcomes of COVID-19 in a group of HIV-positive and HIV-negative patients admitted to a tertiary referral centre in Johannesburg, South Africa. METHODS: Data was collected on all adult patients with known HIV status and COVID-19, confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), admitted to the medical wards and intensive care unit (ICU) between 6 March and 11 September 2020. The data included demographics, co-morbidities, laboratory results, severity of illness scores, complications and mortality, and comparisons were made between the HIV-positive and HIV negative groups. RESULTS: Three-hundred and eighty-four patients, 108 HIV-positive and 276 HIV-negative, were included in the study. Median 4C score was significantly higher in the HIV-positive patients compared to the HIV-negative patients, but there was no significant difference in mortality between the HIV-positive and HIV-negative groups (15% vs 20%, p = 0.31). In addition, HIV-positive patients who died were younger than their HIV-negative counterparts, but this was not statistically significant (47.5 vs 57 years, p = 0.06). CONCLUSION: Our findings suggest that HIV is not a risk factor for moderate or severe COVID-19 disease neither is it a risk factor for mortality. However, HIV-positive patients with COVID-19 requiring admission to hospital are more likely to be younger than their HIV-negative counterparts. These findings need to be confirmed in future, prospective, studies.

The influence of HIV infection and antiretroviral treatment on pulmonary function in individuals in an urban setting in sub-Saharan Africa.

BACKGROUND: With the roll-out of antiretroviral treatment (ART), the life expectancy of people with HIV and, hence, morbidity from non-communicable diseases, including pulmonary diseases, have increased. OBJECTIVES: This research study aims to investigate whether HIV infection and ART use are associated with pulmonary function, given the high frequency of pulmonary infections, including tuberculosis (TB), associated with HIV. METHOD: Adults living with HIV (ART-naïve, on first- or second-line ART), and age and sex matched HIV-negative controls were included in a cross-sectional study in Johannesburg, South Africa. Spirometry was performed to determine lung function, measuring the forced expiratory volume in one second (FEV1), the forced vital capacity (FVC) and the FEV1/FVC ratio before (pre), and after (post), short-acting bronchodilator. The association of HIV infection and ART use with pulmonary function was analysed using linear regression models, adjusting for age, gender, body surface area (BSA), employment, education, smoking and TB. RESULTS: Overall, 548 participants (62% women) were included with a mean age of 38 (standard deviation [s.d.] 9.5) years. No effect of HIV or ART on post-FEV1 was observed in adjusted analysis. Additional adjustment for TB resulted in a higher post-FEV1 in participants on ART compared with HIV-negative participants, whereas TB was associated with a lower FEV1. No effect of HIV and ART on post-FEV1/FVC was observed. CONCLUSION: HIV infection and ART use were not associated with reduced pulmonary function in this urban African population. Tuberculosis showed a mediating effect on the association between HIV, ART and pulmonary function.

Predictors of impaired pulmonary function in people living with HIV in an urban African setting.

BACKGROUND: Studies have associated HIV with an increased risk of obstructive lung disease (OLD). OBJECTIVES: We aimed to identify the predictive factors for impaired lung function in an urban, African, HIV-positive population. METHOD: A cross-sectional study was performed in Johannesburg, South Africa, from July 2016 to November 2017. A questionnaire was administered and pre- and post-bronchodilator spirometry conducted. The predictors investigated included age, sex, antiretroviral treatment (ART) duration, body mass index, history of tuberculosis (TB) or pneumonia, occupational exposure, environmental exposure, smoking and symptoms of OLD (cough, wheeze, mucus and dyspnoea). Impaired lung function was defined as a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of < 0.70, or below the 20th percentile of normal. RESULTS: The 98 ART-naïve participants (mean age = 34.0, standard deviation [s.d.] = 8.2), 85 participants on first-line ART (mean age = 36.9, s.d. = 6.6) and 189 participants on second-line ART (mean age = 43.5, s.d. = 7.9) were predominantly female (65.6%). Of the participants, 64 (17.2%) had impaired lung function and 308 had normal lung function. Linear regression identified age (ß = -0.003, P < 0.01), male sex (ß = -0.016, P = 0.03) and history of TB or pneumonia (ß = -0.024, P < 0.01) as independent predictors of a lower FEV1/FVC ratio. Following logistic regression, only a history of TB or pneumonia (odds ratio = 2.58, 95% confidence interval = 1.47-4.52) was significantly related to impaired lung function (area under the receiver operating characteristic curve = 0.64). CONCLUSION: Our data show that a history of TB or pneumonia predicts impaired lung function. In order to improve timely access to spirometry, clinicians should be alert to the possibility of impaired lung function in people with a history of TB or pneumonia.

Epidemiology of lower respiratory tract infections in adults.

Introduction: Lower respiratory tract infections (LRTIs) are the leading infectious disease cause of death in the world and the fifth overall cause of death. From an epidemiological point of view, most consider pneumonia, influenza, bronchitis (including acute exacerbations in chronic obstructive pulmonary disease [AECOPD]), and bronchiolitis to be the most important LRTIs. Areas covered: This review will describe the epidemiology of LRTIs in adults focusing on community-acquired pneumonia, influenza, and AECOPD, utilizing data from the more recent literature. Expert commentary: LRTIs remain exceedingly common, although there have been significant changes in their epidemiology over recent years, both with regard to their frequency and the infecting pathogens. Part of the change in the epidemiology may relate to changing population demographics, the varying prevalence of smoking, and the introduction of the pneumococcal conjugate vaccine in children and patterns of vaccine usage. Furthermore, antigenic variations in the influenza viruses dictate the frequency and characteristics of the influenza epidemics and pandemics.

Unexpected low frequency of respiratory symptoms in an HIV-positive urban sub-Saharan population compared to an HIV-negative control group.

BACKGROUND: Chronic respiratory illnesses and respiratory infections are common in HIV-positive populations. It seems reasonable that HIV-positive people experience more respiratory symptoms, such as coughing and breathlessness, than those who are HIV-negative. OBJECTIVES: This study aims to determine the frequency of respiratory symptoms in an urban African HIV-positive population. METHOD: A cross-sectional study was conducted in Johannesburg, South Africa, in 2016-2017. Four groups of participants were included: HIV-positive participants (1) not yet on antiretroviral therapy (ART), (2) on first-line ART, (3) on second-line ART and (4) age- and sex-matched HIV-negative controls. Data were collected on socio-demographics, respiratory risk factors and respiratory symptoms. A logistic regression analysis was performed to determine if respiratory symptoms differed between groups and to identify determinants associated with symptoms. RESULTS: Overall, 547 participants were included, of whom 62% were women, with a median age of 37 years. Of these patients, 63% (347) were HIV-positive, 26% were ART-naïve, 24% were on first-line ART and 50% were on second-line ART. Cough and/or productive cough was reported by 27 (5%), wheezing by 9 (2%) and breathlessness by 118 (22%) of the participants. The frequency of these symptoms did not differ by HIV status after adjustment for age and sex. Breathlessness was associated with age, female sex, obesity, a history of respiratory infection and a history of airway hyper-reactivity. CONCLUSION: The frequency of respiratory symptoms was low in our study population except for breathlessness. HIV-positive participants, whether or not on ART, did not experience more symptoms than HIV-negative participants.

How and when to use common biomarkers in community-acquired pneumonia.

Community-acquired pneumonia (CAP) is a leading cause of death in both the developed and developing world. The very young and elderly are especially vulnerable. Even with appropriate early antibiotics we still have not improved the outcomes in these patients since the 1950s, with 30-day case fatality rates of between 10-12%. Interventions to improve outcomes include immunomodulatory agents such as macrolides and corticosteroids. Treating doctors identify CAP patients who are likely to have poor outcomes by using severity scores such as the pneumonia severity index and CURB-65, which allows these patients to be placed in ICU settings from the start of the admission. Another novel way to identify these patients is with the use of biomarkers. This review illustrates how various biomarkers have been shown to predict mortality, complications and response to treatment in CAP patients. The evidence using either procalcitonin or C-reactive protein to demonstrate response to treatment and hence that the antibiotics chosen are appropriate can play an important role in antibiotic stewardship.

A comparison of the pharmacokinetics of Aspen Ceftriaxone and Rocephin in community-acquired meningitis.

BACKGROUND: Community-acquired bacterial meningitis (CABM) is a life-threatening condition that is common among immunocompromised individuals. Intravenous ceftriaxone, of which Rocephin (ROC) is the originator brand, is recommended as first-line therapy in South Africa. Despite concerns regarding therapeutic equivalence with generic agents, this is the first study that has been conducted comparing clinical pharmacokinetics (PK) of a generic ceftriaxone formulation with the originator. OBJECTIVE: To compare the PK and safety of Aspen Ceftriaxone (AC) and ROC in the treatment of adult CABM.Methods. A total of 63 eligible patients were randomised 1:1 to receive 2 g of either medication twice daily for a duration based on the identity of the causative organism and their physician's clinical judgment. The primary endpoint of this study was the comparison of clinical PK, specifically the concentrations of each drug in the cerebrospinal fluid with corresponding paired plasma samples. While this study was underpowered to assess efficacy, safety could be evaluated on the basis of reported adverse events. RESULTS: The two patient groups were epidemiologically similar. There were no statistically significant differences in PK between either agent, nor any difference with regard to safety. CONCLUSION: AC can be considered as equivalent to ROC with regard to PK and safety in patients with CABM.