One-carbon metabolism supplementation improves outcome after stroke in aged male MTHFR-deficient mice.

The prevalence of stroke increases with age and the ability to absorb all nutrients from our diets decreases with age. Nutrition is a modifiable risk factor for stroke, which is a leading cause of death and disability in world-wide. Deficiencies in one­carbon metabolism, including in methyltetrahydrofolate reductase (MTHFR), have been linked to increased risk of stroke. The Mthfr+/- mice mouse model mimic the phenotype of the MTHFR677C➔T polymorphism, such as elevated levels of homocystine. Using this mouse model, the aim of this study was to investigate the impact of dietary supplementation with 5-methylTHF, vitamin B12, and choline after ischemic stroke. Male Mthfr+/- and wildtype littermate control mice were aged (~1.5-year-old) and were placed on control diet (CD) 4-weeks prior to sensorimotor cortex damage using photothrombosis (PT), a model for ischemic stroke. Post-operatively, one group of Mthfr+/- and wildtype littermate mice were placed on 5-methylTHF, vitamin B12, and choline supplemented diet (SD). Four weeks after PT and SD motor function was assessed using the accelerating rotarod, forepaw asymmetry, and ladder beam walking tasks. Total homocysteine and cysteine levels were measured in blood. Brain tissue was processed to assess lesion volume and investigate biochemical and molecular changes. After PT and SD, Mthfr+/- mice were able to stay on the accelerating rotarod longer and used their impaired forepaw to explore more when compared to CD animals. Furthermore, total homocysteine levels in plasma and lesion volume were reduced in Mthfr+/+ and Mthfr+/- SD mice. Within the damage site, there were reduced levels of apoptotic cell death and increased neuroprotective cellular response in the brains of SD treated Mthfr+/- mice. This study reveals a critical role for one­carbon supplementation, with 5-methylTHF, vitamin B12, and choline, in supporting improvement after ischemic stroke damage.

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.

Antibiotic usage in a South African paediatric medical ward following the introduction of an antibiotic prescription chart.

Introduction: the global rise in antibiotic resistance (ABR), coupled with a dry pipeline for the discovery of new antibiotics requires the conservation of currently available antibiotics. Antimicrobial stewardship (AMS) interventions are being implemented to optimize antibiotic use including the use of antibiotic prescription charts. This study reviewed the use of antibiotics before and after the introduction of an antibiotic prescription chart in a paediatric medical ward of an academic tertiary hospital in Johannesburg. Methods: a cross-sectional retrospective review of patient records was conducted for patients admitted to a paediatric medical ward of an academic tertiary hospital over two study periods; before and after the introduction of an antibiotic prescription chart. Data were captured on a Microsoft® Excel (2010) spreadsheet and analyzed using Stata/IC 15.1 (StataCorp, USA). Results: antibiotic use decreased significantly by 7.04% following the introduction of the antibiotic prescription chart (p=0.027). Fields often left unfilled on the antibiotic prescription chart include age (100%), a record of renal function (GFR/CrCl) (97.46%), time of antibiotic prescribing (83.62%) and a record of culture and sensitivity results (80.17%). Conclusion: the findings of this study show an improvement in antibiotic use, the frequency of culture and sensitivity testing and documentation of relevant parameters after the introduction of the antibiotic prescription chart. The use of an antibiotic prescription chart is a practical way to achieve optimal antibiotic use and to encourage proper detailing of the clinical components necessary for antibiotic selection in a hospital setting in a developing country.

An audit of adherence to cervical cancer screening guidelines in a tertiary-level HIV clinic.

Background: Cervical cancer is the most common malignancy affecting South African women aged 15-44 years, with a higher prevalence among women living with HIV (WLWH). Despite recommendations for a screening target of 70%, the reported rate of cervical cancer screening in South Africa is 19.3%. Objectives: To investigate the adherence of healthcare workers to cervical cancer screening guidelines in a tertiary-level HIV clinic. Method: A retrospective cross-sectional record audit of women attending the Charlotte Maxeke Johannesburg Academic Hospital HIV Clinic over a 1-month period. Results: Out of 403 WLWH who attended the clinic, 180 (44.7%) were screened for cervical cancer in the 3 years prior to the index consultation. Only 115 (51.6%) of those women with no record of prior screening were subsequently referred for screening. Women who had undergone screening in the previous 3 years were significantly older (47 years vs 44 years, P = 0.046) and had a longer time since diagnosis of their HIV (12 years vs 10 years, P = 0.001) compared to women who had not undergone screening. There was no significant difference in CD4 count or viral suppression between women who had and had not undergone screening. Conclusion: The rate of cervical cancer screening in our institution is below that recommended by the World Health Organization and the South African National Department of Health.

Clinical and laboratory features of patients with Candida auris cultures, compared to other Candida, at a South African Hospital.

INTRODUCTION: Multidrug resistant Candida auris is an emerging threat worldwide. It has been identified in Africa, however, there is minimal data available comparing C. auris to other Candida species in Africa. METHODOLOGY: Retrospective, case control study at a tertiary South African Hospital. Clinical and laboratory features of patients with positive C. auris clinical cultures from 1 January 2015 to 31 August 2018 were compared to patients who cultured C. albicans and C. glabrata. RESULTS: Forty-five clinical cases with C. auris cultures were identified. The median age was 32 years (IQR = 26-46). The median duration of hospital stay was 64 days (IQR = 39-88) and median time from admission to diagnosis 35 days (IQR = 21-53). Indwelling devices and previous antibiotic exposure were found to be significant risk factors. All C. auris isolates were susceptible to amphotericin B and micafungin. Patients treated with amphotericin B alone, had a higher mortality (73.33%, n = 11/15) than patients treated with an echinocandin (54.55%, n = 6/11), however this was not statistically significant. All C. auris isolates were healthcare associated with 80% (n = 36/45) acquired in ICU. The 30-day all-cause in-patient mortality was 42% (n = 19/45) for C. auris, 36% (n = 16/45) for C. albicans and 53% (n = 24/45) for C. glabrata. CONCLUSIONS: C. auris is an emerging multi drug resistant threat in South Africa. Improved access to echinocandins and improvement of infection prevention and control strategies are imperative to prevent further morbidity and mortality due to this pathogen.

Comparing posttraumatic growth in mothers after stillbirth or early miscarriage.

The possibility of posttraumatic growth in the aftermath of pregnancy loss has received limited attention to date. This study investigated posttraumatic growth in mothers following stillbirth compared to early miscarriage. It was hypothesised that mothers following stillbirth will demonstrate more posttraumatic growth, challenge to assumptive beliefs, and disclosure than mothers following early miscarriage. The study also sought to understand how theoretically-derived variables of the Model of Growth in Grief (challenge to assumptive beliefs and disclosure) explained unique variance in posttraumatic growth when key factors were controlled for. One-hundred and twenty women who had experienced a stillbirth (N = 57) or early miscarriage (N = 63) within the last two to six years completed validated questionnaires in an online survey relating to posttraumatic growth and key variables relevant to emotional adjustment post-bereavement. Participants who had experienced a stillbirth demonstrated significantly higher levels of posttraumatic growth, posttraumatic stress symptoms, perinatal grief, disclosure, challenge to assumptive beliefs and rumination than participants who had experienced an early miscarriage (Cohen's d ranged .38-.94). In a hierarchical stepwise regression analysis, challenge to assumptive beliefs alone predicted 17.5% of the variance in posttraumatic growth. Intrusive and deliberate rumination predicted an additional 5.5% of variance, with urge to talk, reluctance to talk, and actual self-disclosure predicting a further 15.3%. A final model including these variables explained 47.9% of the variance in posttraumatic growth. Interventions targeting challenge to assumptive beliefs, disclosure, and rumination are likely to be clinically useful to promote psychological adjustment in mothers who have experienced stillbirth and early miscarriage.

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.].

Outcomes of flucytosine-containing combination treatment for cryptococcal meningitis in a South African national access programme: a cross-sectional observational study.

BACKGROUND: Although flucytosine is a key component of WHO-recommended induction treatment for HIV-associated cryptococcal meningitis, this antifungal agent is not widely available in low-income and middle-income countries due to limited production and cost. In 2018, a national flucytosine access programme was initiated in South Africa. We aimed to determine the effectiveness of flucytosine-containing induction regimens in routine care to motivate for the urgent registration of flucytosine and its inclusion in treatment guidelines. METHODS: In this cross-sectional study, we compared outcomes of adults aged 18 years and older with incident laboratory-confirmed cryptococcal meningitis treated with or without flucytosine-containing regimens at 19 sentinel hospitals in South Africa. A case of cryptococcosis was defined as illness in an adult with: (1) positive cerebrospinal fluid (CSF) India ink microscopy; (2) a positive CSF cryptococcal antigen test; or (3) culture of Cryptococcus neoformans or Cryptococcus gattii from CSF or any other specimen. We excluded patients without a case report form, those with an unknown or negative HIV serology result, those with a recurrent episode, and those who did not receive antifungal treatment in hospital. We assessed cumulative in-hospital mortality at 14 days and 30 days and calculated the overall crude in-hospital case-fatality ratio. We used random-effects logistic regression to examine the association between treatment group and in-hospital mortality. FINDINGS: From July 1, 2018, to March 31, 2020, 10 668 individuals were diagnosed with laboratory-confirmed cryptococcal meningitis, 7787 cases diagnosed at non-enhanced surveillance sites and 567 cases from eight enhanced surveillance sites with no access to flucytosine were excluded. Of 2314 adults with a first episode of cryptococcosis diagnosed at 19 facilities with access to flucytosine, 1996 had a case report form and of these, 1539 received induction antifungal treatment and were confirmed HIV-seropositive first-episode cases. Of 1539 patients who received antifungal therapy, 596 (38·7%) individuals received a flucytosine-containing regimen and 943 (61·3%) received another regimen. The median age was 36 years (IQR 32-43) and 906 (58·9%) participants were male and 633 (41·1%) were female. The crude in-hospital case-fatality ratio was 23·9% (95% CI 20·0-27·0; 143 of 596) in those treated with flucytosine-containing regimens and 37·2% (95% CI 34·0-40·0; 351 of 943) in those treated with other regimens. Patients admitted to non-academic hospitals (adjusted odds ratio [aOR] 1·95 [95% CI 1·53-2·48]; p<0·0001) and those who were antiretroviral treatment-experienced (aOR 1·30 [1·02-1·67]; p=0·033) were more likely to receive flucytosine. After adjusting for relevant confounders, flucytosine treatment was associated with a 53% reduction in mortality (aOR 0·47 [95% CI 0·35-0·64]; p<0·0001). Among survivors, the median length of hospital admission in the flucytosine group was 11 days (IQR 8-15) versus 17 days (13-21) in the comparison group (p=0·0010). INTERPRETATION: In-hospital mortality among patients treated with a flucytosine-containing regimen was comparable to reduced mortality reported in patients receiving a flucytosine-containing regimen in a recent multicentre African clinical trial. Flucytosine-based treatment can be delivered in routine care in a middle-income country with a substantial survival benefit. FUNDING: National Institute for Communicable Diseases, a Division of the National Health Laboratory Service. TRANSLATION: For the Zulu translation of the abstract see Supplementary Materials section.

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.

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.

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.

Examining the levels of acetylation, DNA methylation and phosphorylation in HIV-1 positive and multidrug-resistant TB-HIV patients.

OBJECTIVES: In this study, we examined the impact of epigenetic modifications on host gene functioning by assessing the expression of seven candidate genes in three separate groups including healthy, multidrug-resistant (MDR) TB-HIV co-infected and HIV-1 positive individuals. METHODS: Ten patients with MDR TB and HIV-1 co-infection on TB and HIV therapy and a cohort comprised of 10 newly diagnosed individuals with HIV-1 infection were recruited from the TB and HIV clinics at the Charlotte Maxeke Johannesburg Academic Hospital. Notably, the HIV-1 positive individuals were not placed on antiretroviral therapy (ART) at the time of recruitment and blood collection. A third group consisting of 10 healthy participants without MDR TB or HIV infection was recruited from the University of the Witwatersrand. Blood samples collected from all three cohorts were employed for extraction of plasma, total RNA and genomic DNA. RESULTS: Our data indicated that the expression of DNA methyltransferase 1 (DNMT1) and Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) genes was significantly increased in HIV-1 positive patients and was lowest in MDR TB-HIV co-infected patients. By contrast, histone acetyltransferase (HAT), histone deacetylase (HDAC), protein tyrosine kinase (PtkA) and protein tyrosine phosphatase (PtpA) mRNA expression levels were substantially enhanced in HIV-1 infected and were lowest in healthy individuals. Conversely, Dicer expression levels were comparable among all three study groups. CONCLUSION: Promising preliminary data emanating from this investigation may potentially be used for generation of novel vaccines and therapeutic compounds capable of neutralising MDR TB-HIV and HIV-1 infection.

Survey of Patient's Experience of Altruistic Nondirected Kidney Donation.

The scarcity of organs for donation is an ongoing issue. Change in legislative framework allows for altruistic donations in the UK, but, whereas the number of donations from deceased donors has increased, there has been a slow decline in altruistic living donors. The aim of this study was to review perspectives of altruistic nondirected kidney donors (ANDKD) at our center and outcome of all enquiries to inform service improvement and increase the numbers of donors. All enquiries by potential ANDKD at our center from September 2005 to September 2017 were analyzed. Donor assessment was performed as per the UK Guidelines, prior to obtaining Human Tissue Authority approval. The outcome of donation and results of questionnaires sent to 50 ANDKD were analyzed. During the period, 51 of the 180 enquiries (28.3%) resulted in kidney donation. Questionnaire responses were: 66% donors were retired; most heard about altruistic donation through media (60%); 72% thought psychological or psychiatric assessment was necessary; 95% found the information provided prior to donation adequate; 82% rated their overall experience as good/excellent; and 90% would recommend kidney donation to others. Thirteen of 50 donated kidneys were fed into the kidney exchange program. The mean ± standard error of the mean of the duration from human tissue authority approval to donation were 60.4 ± 5.4 and 131.2 ± 11.2 days, respectively (P = 0.00001). A significant proportion of enquiries for altruistic donation would result in donation but the assessment process needs to be quicker. ANDKD is useful way of priming the National Living Donor Kidney Sharing Scheme.

Distinct epigenetic regulation in patients with multidrug-resistant TB-HIV co-infection and uninfected individuals.

BACKGROUND: Mycobacterium tuberculosis (Mtb) is an airborne pathogenic microorganism that causes tuberculosis (TB). This pathogen invades lung tissues causing pulmonary infections and disseminates into other host organs. The Bacillus Calmette-Guérin (BCG) vaccine is employed to provide immune protection against TB; however, its efficacy is dependent on the age, immune status and geographic location of vaccinated individuals. Advanced diagnostic approaches such as GeneXpert MTB/RIF® and line probe assays (LPAs) have allowed rapid detection of drug-resistant, multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb strains. However, in sub-Saharan Africa, public and private health institutions are further burdened by the high prevalence of Human Immunodeficiency Virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS) and TB co-infections across different age groups. Epigenetic mechanisms have been widely exploited by Mtb and HIV to bypass the host's innate and adaptive immune responses, leading to microbial proliferation and disease manifestation. In the current study, we investigated the impact of epigenetic mechanisms in regulating target gene expression in healthy and patients co-infected with MDR TB-HIV.

Morbidity Following Hand-Assisted Laparoscopic Donor Nephrectomy.

Background: The incidence of morbidity and readmission rate after hand-assisted laparoscopic donor nephrectomy (HALDN) is not clear. Aims: Our study aims to review our experience with HALDN, mainly the reasons for patient readmissions. Methods: Prospectively collected data on all patients undergoing HALDNs between August 2007 and June 2015 were retrieved. The primary outcome was 30-day readmission rate. Secondary outcomes were complications and readmission etiology. Results: There were 161 nephrectomies with a median age of 51 years, 72 (44.7%) men, and 114 (70.8%) left-sided operations. Twenty-one (13%) individuals were readmitted within 30 days. There were total 25 (15.5%) readmissions during the study period. The characteristics of patients readmitted and patients not readmitted were broadly similar. Nine of 21 (43%) individuals readmitted had nonspecific findings (nonspecific findings on imaging, negative blood cultures, and raised inflammatory markers). The reasons for readmission were unrelated to nephrectomy in 24% and 19% required surgery for complications unrelated to nephrectomy. Conclusion: We observed a high readmission rate after HALDN. A significant proportion of readmissions were due to nonspecific abdominal pain associated with raised inflammatory markers and no obvious source of sepsis. Living donors should be fully informed about the risks including the possibility of complications unrelated to HALDN.

Low-dose ritonavir-boosted darunavir once daily versus ritonavir-boosted lopinavir for participants with less than 50 HIV RNA copies per mL (WRHI 052): a randomised, open-label, phase 3, non-inferiority trial.

BACKGROUND: Pilot studies suggest that ritonavir-boosted darunavir could show high efficacy at doses below those currently approved. We investigated whether switch to 400 mg of darunavir boosted with 100 mg ritonavir once daily could show equivalent efficacy to continuation of ritonavir-boosted lopinavir (a protease inhibitor commonly used in low-income and middle-income countries) for individuals with HIV RNA suppression. METHODS: In the WRHI 052 study, a randomised, parallel-group, open-label, non-inferiority phase 3 trial, adults who were HIV-1 positive were enrolled in Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa. Eligible participants were 18 years or older, who tolerated ritonavir-boosted lopinavir in combination with two nucleoside analogues (standard of care) for 6 months or more, and had plasma HIV-1 RNA of less than 50 copies per mL within 60 days of enrolment. We randomly assigned participants (1:1), using a computer-generated randomisation plan, to switch to darunavir (400 mg) boosted with ritonavir (100 mg) once daily or remain on ritonavir-boosted lopinavir (800 mg [plus 200 mg ritonavir]), with nucleoside analogues left unchanged. The primary endpoint was the proportion of patients with less than 50 HIV-1 RNA copies per mL at week 48 (US Food and Drug Administration snapshot algorithm; non-inferiority margin -4%). Primary and safety analyses included participants receiving at least one dose of darunavir boosted with ritonavir. This trial is registered with ClinicalTrials.gov, number NCT02671383. FINDINGS: Between June 30, 2016, and June 15, 2017, 148 participants were assigned to ritonavir-boosted darunavir 400 mg and 152 continued on their lopinavir-containing regimen. Four (3%) patients in the darunavir group and three (2%) in the lopinavir group discontinued before week 48. At week 48, darunavir was non-inferior to lopinavir for the primary outcome (142 [96%] of 148 participants on darunavir had <50 HIV-1 RNA copies per mL vs 143 [94%] of 152 participants on lopinavir; difference 1·9% [95% CI -3·4 to 7·3]), with a predefined margin of -4%. More participants taking darunavir (30 [20%] participants) had drug-related adverse events than those on lopinavir (eight [5%]), but the adverse events were generally asymptomatic and resolved when switching back to lopinavir. Elevated liver transaminase in three (1%; one symptomatic) darunavir participants led to study withdrawal; all transaminase elevations resolved on restarting lopinavir. INTERPRETATION: Low-dose ritonavir-boosted darunavir might be a safe and efficacious switch option to maintain HIV suppression for patients on lopinavir. However, an adequately powered and designed study in viraemic participants is needed. FUNDING: South African Medical Research Council, United States Agency for International Development, and US National Institute of Allergy and Infectious Diseases.

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.

First insights into species and genotypes of Echinococcus in South Africa.

Cystic echinococcosis is a serious and neglected parasitic zoonosis that is regarded as an emerging disease world-wide. Effective control of the disease is based on understanding the variability of Echinococcus granulosus (sensu lato), as genotypic characteristics may influence lifecycle patterns, development rate, and transmission. No molecular epidemiological research has previously been conducted to shed light on genotypes responsible for the disease in South Africa. To identify strains circulating in the country, parasite material was collected from patients between August 2010 and September 2012 and analyzed by PCR/RFLP methods. A total of 32 samples was characterized as E. granulosus sensu stricto (G1-G3) (81%), E. canadensis (G6/7) (16%) and E. ortleppi (G5) (3%). Furthermore, two co-amplifying G6/7 genotypes were confirmed as G7 by sequencing. This is the first report on genotyping of Echinococcus species in South Africa, and, to the best of our knowledge, the first report of the G5 and G7 genotypes from humans in Africa.