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We determined the effect of HIV infection on deaths among persons >18 months of age with culture-confirmed candidemia at 29 sentinel hospitals in South Africa during 2012-2017. Of 1,040 case-patients with documented HIV status and in-hospital survival data, 426 (41%) were HIV-seropositive. The in-hospital case-fatality rate was 54% (228/426) for HIV-seropositive participants and 37% (230/614) for HIV-seronegative participants (crude odds ratio [OR] 1.92, 95% CI 1.50-2.47; p<0.001). After adjusting for relevant confounders (n = 907), mortality rates were 1.89 (95% CI 1.38-2.60) times higher among HIV-seropositive participants than HIV-seronegative participants (p<0.001). Compared with HIV-seronegative persons, the stratum-specific adjusted mortality OR was higher among HIV-seropositive persons not managed in intensive care units (OR 2.27, 95% CI 1.47-3.52; p<0.001) than among persons who were (OR 1.56, 95% CI 1.00-2.43; p = 0.05). Outcomes among HIV-seropositive persons with candidemia might be improved with intensive care. [ABSTRACT FROM AUTHOR]

Background: Sensory neuropathy (SN) is a common and often painful neurological condition associated with HIV‐infection and its treatment. However, data on the incidence of SN in neuropathy‐free individuals initiating combination antiretroviral therapies (cART) that do not contain the neurotoxic agent stavudine are lacking. Aims: We investigated the 6‐month incidence of SN in ART naïve individuals initiating tenofovir (TDF)‐based cART, and the clinical factors associated with the development of SN. Methods: 120 neuropathy‐free and ART naïve individuals initiating cART at a single center in Johannesburg, South Africa were enrolled. Participants were screened for SN using clinical signs and symptoms at study enrolment and approximately every 2‐months for a period of ~6‐months. Diagnostic criteria for symptomatic SN was defined by the presence of at least one symptom (pain/burning, numbness, paraesthesias) and at least two clinical signs (reduced vibration sense, absent ankle reflexes or pin‐prick hypoaesthesia). Diagnostic criteria for asymptomatic SN required at least two clinical signs only (as above). Results: A total of 88% of the cohort completed three visits within the 6‐month period. The 6‐month cumulative incidence of neuropathy was 140 cases per 1000 patients (95% CI: 80‐210) at an incidence rate of 0.37 (95% CI: 0.2‐0.5) per person year. Height and active tuberculosis (TB) disease were independently associated with the risk of developing SN (P <.05). Interpretation: We found that within the first 6 months of starting cART, incident SN persists in the post‐stavudine era, with 11 (9%) of individuals developing asymptomatic SN, and 9 (8%) developing symptomatic SN. [ABSTRACT FROM AUTHOR]

Background: HIV-infected persons are at increased risk of opportunistic infections, including invasive nontyphoidal Salmonella (iNTS) infections; antiretroviral therapy (ART) reduces this risk. We explored changing iNTS incidence associated with increasing ART availability in South Africa. Methods: Laboratory-based surveillance for iNTS was conducted in Gauteng Province, South Africa, with verification using the National Health Laboratory Service’s Central Data Warehouse (CDW), between 2003 and 2013. Isolates were serotyped at the Centre for Enteric Diseases. CDW data on patient numbers obtaining HIV viral load measurements provided estimates of numbers of HIV-infected patients receiving ART. A Poisson regression model was used to measure the changing incidence of iNTS infection from 2003 to 2013. The correlation between the incidence of iNTS and ART use from 2004 to 2013 was determined using Pearson’s correlation coefficient. Results: From 2003–2013, the incidence of iNTS per 100,000 population per year decreased from 5.0 to 2.2 (p < .001). From 2004 to 2013, the incidence per 100,000 population of HIV viral load testing increased from 75.2 to 3,620.3 (p < .001). The most common serotypes causing invasive disease were Salmonella enterica serovar Typhimurium (Salmonella Typhimurium), and Salmonella Enteritidis: 2,469 (55.4%) and 1,156 (25.9%) of 4,459 isolates serotyped, respectively. A strong negative correlation was observed between decreasing iNTS incidence and increasing ART use from 2004 to 2013 (r = -0.94, p < .001). Similarly, decreasing incidence of invasive Salmonella Typhimurium infection correlated with increasing ART use (r = -0.93, p < .001). Incidence of invasive Salmonella Enteritidis infection increased, however (r = 0.95, p < .001). Between 2003 and 2004, fewer adult men than women presented with iNTS (male-to-female rate ratio 0.73 and 0.89, respectively). This was reversed from 2005 through 2013 (ranging from 1.07 in 2005 to 1.44 in 2013). Adult men accessed ART less (male-to-female rate ratio ranging from 0.61 [2004] to 0.67 [2013]). Conclusions: The incidence of iNTS infections including Salmonella Typhimurium decreased significantly in Gauteng Province in association with increased ART utilization. Adult men accessed ART programs less than women, translating into increasing iNTS incidence in this group. Monitoring iNTS incidence may assist in monitoring the ART program. Increasing incidence of invasive Salmonella Enteritidis infections needs further elucidation. [ABSTRACT FROM AUTHOR]

Introduction: Streptococcus pneumoniae is the commonest cause of bacteremic pneumonia among HIV-infected persons. As more countries with high HIV prevalence are implementing infant pneumococcal conjugate vaccine (PCV) programs, we aimed to describe the baseline clinical characteristics of adult invasive pneumococcal disease (IPD) in the pre-PCV era in South Africa in order to interpret potential indirect effects following vaccine use. Methods: National, active, laboratory-based surveillance for IPD was conducted in South Africa from 1 January 2003 through 31 December 2008. At 25 enhanced surveillance (ES) hospital sites, clinical data, including HIV serostatus, were collected from IPD patients ≥ 5 years of age. We compared the clinical characteristics of individuals with IPD in those HIV-infected and -uninfected using multivariable analysis. PCV was introduced into the routine South African Expanded Program on Immunization (EPI) in 2009. Results: In South Africa, from 2003–2008, 17 604 cases of IPD occurred amongst persons ≥ 5 years of age, with an average incidence of 7 cases per 100 000 person-years. Against a national HIV-prevalence of 18%, 89% (4190/4734) of IPD patients from ES sites were HIV-infected. IPD incidence in HIV-infected individuals is 43 times higher than in HIV-uninfected persons (52 per 100 000 vs. 1.2 per 100 000), with a peak in the HIV-infected elderly population of 237 per 100 000 persons. Most HIV-infected individuals presented with bacteremia (74%, 3 091/4 190). HIV-uninfected individuals were older; and had more chronic conditions (excluding HIV) than HIV-infected persons (39% (210/544) vs. 19% (790/4190), p<0.001). During the pre-PCV immunization era in South Africa, 71% of serotypes amongst HIV-infected persons were covered by PCV13 vs. 73% amongst HIV-uninfected persons, p = 0.4, OR 0.9 (CI 0.7–1.1). Conclusion: Seventy to eighty-five percent of adult IPD in the pre-PCV era were vaccine serotypes and 93% of cases had recognized risk factors (including HIV-infection) for pneumococcal vaccination. These data describe the epidemiology of IPD amongst HIV-infected and -uninfected adults during the pre-PCV era and provide a robust baseline to calculate the indirect effect of PCV in future studies. [ABSTRACT FROM AUTHOR]

Toxoplasmosis is an infection of warm-blooded vertebrates caused by one of the most common parasites of humans, Toxoplasma gondii. T. gondii is an obligate intracellular protozoan parasite with a worldwide distribution and a varying prevalence between different continents and countries, and even within the same country. There is little known about T. gondii prevalence in Africa. In South Africa, there is limited information about the disease and detailed recent demographic data of groups at risk are missing. The seroprevalences of T. gondii antibodies in samples of selected populations, namely HIV-positive male and female subjects, and HIV-negative pregnant women in the Gauteng province, were therefore investigated and found to be 9.8% (95% confidence interval: 7.1%-13.4%) and 12.8 % (CI: 8.9%-15.8%), respectively. A more general population sample (but biased towards pregnant women) showed a 6.4% (CI: 4.5%-9%) seroprevalence. These results show that T. gondii infection is present in South Africa, but its prevalence is much lower than previously reported in this region. While the burden of disease has been reduced in recent times, a low prevalence means that more previously unexposed people are at risk of acquiring an acute infection, which may cause congenital disease in pregnant women, or which, in reactivation form, may ultimately be life-threatening in HIV/AIDS patients. [ABSTRACT FROM AUTHOR]

Background: Highly active antiretroviral treatment (HAART) programs have been associated with declines in the burden of invasive pneumococcal disease (IPD) in industrialized countries. The aim of this study was to evaluate trends in IPD hospitalizations in HIV-infected adults in Soweto, South Africa, associated with up-scaling of the HAART program from 2003 to 2008. Methods: Laboratory-confirmed IPD cases were identified from 2003 through 2008 through an existing surveillance program. The period 2003-04 was designated as the early-HAART era, 2005-06 as the intermediate-HAART era and 2007-08 as the established-HAART era. The incidence of IPD was compared between the early-HAART and established-HAART eras in HIV-infected and-uninfected individuals. Results: A total of 2,567 IPD cases among individuals older than 18 years were reported from 2003 through 2008. Overall incidence of IPD (per 100,000) did not change during the study period in HIV-infected adults (207.4 cases in the early-HAART and 214.0 cases in the established-HAART era; p = 0.55). IPD incidence, actually increased 1.16-fold (95% CI: 1.01; 1.62) in HIV-infected females between the early-and established-HAART eras (212.1 cases and 246.2 cases, respectively; p = 0.03). The incidence of IPD remained unchanged in HIV-uninfected adults across the three time periods. Conclusion: Despite a stable prevalence of HIV and the increased roll-out of HAART for treatment of AIDS patients in our setting, the burden of IPD has not decreased among HIV-infected adults. The study indicates a need for ongoing monitoring of disease and HAART program effectiveness to reduce opportunistic infections in African adults with HIV/AIDS, as well as the need to consider alternate strategies including pneumococcal conjugate vaccine immunization for the prevention of IPD in HIV-infected adults. [ABSTRACT FROM AUTHOR]

We investigated reasons for clinical follow-up and treatment discontinuation among HIV-infected individuals receiving antiretroviral therapy (ART) in a public-sector clinic and in a workplace clinic in South Africa. Participants in a larger cohort study who had discontinued clinical care by the seventh month of treatment were traced using previously provided locator information. Those located were administered a semistructured questionnaire regarding reasons for discontinuing clinical follow-up. Participants who had discontinued antiretroviral therapy were invited to participate in further in-depth qualitative interviews. Fifty-one of 144 (35.4%) in the workplace cohort had discontinued clinical follow-up by the seventh month of treatment. The median age of those who discontinued follow-up was 46 years and median educational level was five years. By contrast, only 16.5% (44/267) of the public-sector cohort had discontinued follow-up. Among them the median age was 37.5 years and median education was 11 years. Qualitative interviews were conducted with 17 workplace participants and 10 public-sector participants. The main reasons for attrition in the workplace were uncertainty about own HIV status and above the value of ART, poor patient-provider relationships and workplace discrimination. In the public sector, these were moving away and having no money for clinic transport. In the workplace, efforts to minimize the time between testing and treatment initiation should be balanced with the need to provide adequate baseline counseling taking into account existing concepts about HIV and ART. In the public sector, earlier diagnosis and ART initiation may help to reduce early mortality, while links to government grants may reduce attrition. [ABSTRACT FROM AUTHOR]

Background. Conflicting reports exist regarding the impact of human immunodeficiency virus (HIV) infection on the risk of severe malaria. We aimed to assess the effect of HIV infection status, advancing immunosuppression, and antimalarial immunity on the severity of malaria. Methods. A prospective cohort study was conducted. Consecutive hospitalized adult patients with falciparum malaria were tested for HIV antibodies and to determine CD4+ T cell count. Immunity to malaria was assessed by obtaining a history of childhood residence in an area where malaria is endemic. Patients were assessed for features of severe malaria. Results. Three hundred thirty-six patients were enrolled in the study, of whom 32 (10%) had severe malaria. The prevalence of HIV infection was 33%, and 111 patients (33%) were nonimmune to malaria. HIV-infected patients complained more frequently about respiratory and abdominal symptoms and less frequently about rigors and headache. Risk factors for severe malaria determined by multivariate analysis included being nonimmune to malaria, having a positive HIV serostatus, having an elevated parasite count, and having an increased white blood cell count. Risk of severe malaria was increased in HIV-infected patients with a CD4+ T cell count of <200×106 cells/L (P ⩽.001). Nonimmune HIV-infected patients were significantly more likely to have severe malaria (13 P ⩽.001 [36%] of 36 patients) than were nonimmune non-HIV-infected patients (9 [12%] of 75 patients; odds ratio, 4.15 [95% confidence interval, 1.57-10.97]; ). HIV serostatus did not affect risk of severe malaria in the group P = .003 from an area with endemicity (5 [7%] of 74 HIV-infected patients had severe malaria, and 5 [3%] of 151 non- HIV-infected patients had malaria; ). P = .248 Conclusions. HIV-infected nonimmune adults are at increased risk of sever malaria. This risk is associated with a low CD4+ T cell count. This interaction is of great public health importance. [ABSTRACT FROM AUTHOR]

The article presents a study that investigates the prevalence of Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations in HIV-positive patients with Pneumocystis Pneumonia in South Africa and its correlation with sulfa prophylaxis and clinical outcome. Results show that the general use of sulfa drugs is exerting a selective pressure on Pneumocystis jirovecii strains containing DHPS mutations.

In South Africa, patients should initiate ART according to the current national guideline.[1],[11],[12] Screening for subclinical cryptococcal disease has a proven mortality benefit among HIV-seropositive patients with low CD4 counts. The absence of symptoms of meningitis does not exclude CM: approximately one in three patients with asymptomatic cryptococcal antigenaemia has concurrent CM.[18] CrAg-positive patients who are subsequently identified as having CM should be managed as per Recommendation 3. If the patient does not have new symptoms or signs of meningitis, the clinician should ensure that the patient receives adequate fluconazole maintenance therapy (refer to Recommendation 3). Patients without focal neurological signs should then be referred to a centre where LP can be performed, while patients with focal neurological signs need to have a CT brain scan performed first followed by an LP (if this is not contraindicated by CT brain findings). Approximately 15% of patients with initially normal intracranial pressure will develop raised intracranial pressure during treatment; thus, all patients should be monitored daily for headache or signs of raised intracranial pressure that should prompt an LP. [Extracted from the article]

Investigated the knowledge, attitudes, beliefs and practices of HIV-infected individuals regarding HIV/AIDS and antiretroviral therapy (ART) in an HIV outpatient clinic in Soweto, South Africa. Potential barriers to ART adherence; High knowledge scores about HIV, including the cause, mode of transmission and progression of disease, among the study patients; Results suggesting an excessively high confidence in ART.