Virologic failure and second-line antiretroviral therapy in children in South Africa--the IeDEA Southern Africa collaboration

Article approval pendingWith expanding pediatric antiretroviral therapy (ART) access, children will begin to experience treatment failure and require second-line therapy. We evaluated the probability and determinants of virologic failure and switching in children in South Africa

Monitoring the South African National Antiretroviral Treatment Programme, 2003-2007: the IeDEA Southern Africa collaboration.

OBJECTIVES: To introduce the combined South African cohorts of the International epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration as reflecting the South African national antiretroviral treatment (ART) programme; to characterise patients accessing these services; and to describe changes in services and patients from 2003 to 2007. DESIGN AND SETTING: Multi-cohort study of 11 ART programmes in Gauteng, Western Cape, Free State and KwaZulu-Natal. SUBJECTS: Adults and children (<16 years old) who initiated ART with > or =3 antiretroviral drugs before 2008. RESULTS: Most sites were offering free treatment to adults and children in the public sector, ranging from 264 to 17,835 patients per site. Among 45,383 adults and 6,198 children combined, median age (interquartile range) was 35.0 years (29.8-41.4) and 42.5 months (14.7-82.5), respectively. Of adults, 68% were female. The median CD4 cell count was 102 cells/microl (44-164) and was lower among males than females (86, 34-150 v. 110, 50-169, p<0.001). Median CD4% among children was 12% (7-17.7). Between 2003 and 2007, enrolment increased 11-fold in adults and 3-fold in children. Median CD4 count at enrolment increased for all adults (67-111 cells/microl, p<0.001) and for those in stage IV (39-89 cells/microl, p<0.001). Among children <5 years, baseline CD4% increased over time (11.5-16.0%, p<0.001). CONCLUSIONS: IeDEA-SA provides a unique opportunity to report on the national ART programme. The study describes dramatically increased enrolment over time. Late diagnosis and ART initiation, especially of men and children, need attention. Investment in sentinel sites will ensure good individual-level data while freeing most sites to continue with simplified reporting

The future of viral infections

Since the onset of the COVID-19 pandemic there is increasing scientific interest in animal viruses and their future cross-species transmission potential. Although viruses are the most diverse and abundant of living organisms, we know less about their diversity, evolution, and cross-species transmission potential than other living organisms. Few animal species, mainly those located in the phylum Chordata have been surveyed for viruses, while surveillance among invertebrate species has mainly focussed on common disease vectors such as ticks and mosquitoes, both located in the phylum arthropoda, one of 21 invertebrate phyla. The recent advent of metagenomic next-generation sequencing has however begun to advance the study of the animal virome, revealing novel biodiversity insights. For example, while bats and rodents have been shown to harbour a wide range of coronaviruses, recent molecular explorations have documented coronaviruses in other vertebrates such as amphibians and fish

Guidelines for the management of HIV-infected children (National Department of Health, South Africa, 2005): A summary of antiretroviral treatment guidelines

National guidelines for the management of HIV-infected children in South Africa have been developed as a consensus document by practising HIV clinicians around the country. Guidelines for antiretroviral (ARV) management of children appear in a booklet distributed by the National Department of Health (DoH) since mid-2004 (National Antiretroviral Treatment Programme Guideline for Carers, National Department of Health, South Africa, 2004). A comprehensive booklet on management of HIV-infected children has also been produced for the DoH which includes recommendations on management with antiretroviral (ARV) therapy. The South African national paediatric guidelines are based on the recommendations provided by the World Health Organization (WHO) (Scaling up antiretroviral therapy in resource limited settings; treatment guidelines for a public health approach WHO 2003). It is important to note that WHO are updating their recommendations. Based on this some amendments, e.g. the staging system, have already been incorporated into the final version of the South African national guidelines. Other recommendations are more recent and have yet to undergo broader review. These have therefore not formed part of the printed version of the South African guidelines. It is anticipated that a process of updating the guidelines needs to be put in place urgently. The national guidelines are available on the government website (www.health.gov.za), and clinicians are advised to update themselves regularly at this website for any amendments that may be made to the guidelines

Early mortality and loss to follow-up in HIV-infected children starting antiretroviral therapy in Southern Africa.

BACKGROUND: Many HIV-infected children in Southern Africa have been started on antiretroviral therapy (ART), but loss to follow up (LTFU) can be substantial. We analyzed mortality in children retained in care and in all children starting ART, taking LTFU into account. PATIENTS AND METHODS: Children who started ART before the age of 16 years in 10 ART programs in South Africa, Malawi, Mozambique, and Zimbabwe were included. Risk factors for death in the first year of ART were identified in Weibull models. A meta-analytic approach was used to estimate cumulative mortality at 1 year. RESULTS: Eight thousand two hundred twenty-five children (median age 49 months, median CD4 cell percent 11.6%) were included; 391 (4.8%) died and 523 (7.0%) were LTFU in the first year. Mortality at 1 year was 4.5% [95% confidence interval (CI): 2.8% to 7.4%] in children remaining in care, but 8.7% (5.4% to 12.1%) at the program level, after taking mortality in children and LTFU into account. Factors associated with mortality in children remaining in care included age [adjusted hazard ratio (HR) 0.37; 95% CI: 0.25 to 0.54 comparing > or =120 months with <18 months], CD4 cell percent (HR: 0.56; 95% CI: 0.39 to 0.78 comparing > or =20% with <10%), and clinical stage (HR: 0.12; 95% CI: 0.03 to 0.45 comparing World Health Organization stage I with III/IV). CONCLUSIONS: In children starting ART and remaining in care in Southern Africa mortality at 1 year is <5% but almost twice as high at the program level, when taking LTFU into account. Age, CD4 percentage, and clinical stage are important predictors of mortality at the individual level

Ralstonia Mannitolilytica: An increasingly recognized healthcare-associated pathogen

Ralstonia&nbsp;species are more frequently being recognised as causative agents of serious healthcare-associated infection especially among immunocompromised individuals. Ralstonia species are environmental, non-fermenting, aerobic, Gram-negative bacilli typically found in water and soil. Ralstonia mannitolilytica,&nbsp;Ralstonia pickettii&nbsp;and&nbsp;Ralstonia insidiosa have been responsible for human infections such as bacteraemia and bone infection. Central nervous system infection and infection in immune competent individuals are uncommon. We report a case of ventriculoperitoneal shunt infection and meningitis caused by&nbsp;R. mannitolilytica in an immune competent 11-month-old female.&nbsp;&nbsp

Neurological and neurocognitive function of HIV-infected children commenced on antiretroviral therapy

Aim: To describe neurological and neurocognitive deficits in HIV-infected children and the short-term effect of highly active antiretroviral therapy (HAART) on the observed deficits. Methods: In this prospective study, 39 children (15 females) were evaluated before the start of HAART and 30 reassessed 6 months later. The subjects were evaluated with a range of cognitive tests used in everyday clinical practice. Results: At enrolment, the mean (±SD) age was 60±46 months, 17 (44%) and 22 (56%) had Centers for Disease Control (CDC) clinical category B and C disease respectively, and 36 (92%) had severe immunosuppression. At the start of HAART no child had cranial nerve or cerebellar dysfunction, but 13/29 (33.3%) had evidence of motor dysfunction. By 6 months 1 child had developed cerebellar dysfunction, but there was no statistically significant change in the frequency of motor dysfunction. Mean baseline performances on cognitive testing were generally subnormal. Between 33% and 81% of the children recorded subnormal intelligence quotients on various cognitive tests. Mean performances did not change significantly after 6 months of HAART. Conclusion: Neurological and neurocognitive deficits are frequent in HIV-infected children. The prevalence and extent of deficits did not change significantly in response to short-term HAART, indicating neither spontaneous improvement nor deterioration during early treatment

HIV-infected infants born to women who tested HIV-negative during pregnancy

The prevention of mother-to-child transmission (PMTCT) programme in the Western Cape is said to have achieved 100% coverage.1 This implies that all pregnant women who attend an antenatal health care facility in the public sector are offered voluntary counselling and testing (VCT). Uptake varies but has been reported to be as high as 90% in the Guguletu district.1 Currently, women who test HIV-positive qualify for the nevirapine-based PMTCT programme. Transmission rates below 10% have been achieved in some health districts (Médecins sans Frontières — unpublished research). Mothers of several perinatally infected infants recently diagnosed in our institution have indicated that they tested HIV-negative during their pregnancy. In some cases we have verified their statements with clinical and laboratory documentation. There is a need to determine the frequency of this phenonomen. Pregnant women are encouraged to book at their nearest antenatal clinic before 5 months’ gestation, although this frequently does not occur. We are concerned about women who do book early and test HIV-negative. Some may be in the ‘window period’ of the infection or become infected from a sexual partner during the latter stages of pregnancy. At present, there is no provision within the PMTCT programme for repeat HIV testing during pregnancy. Some women may, therefore, be denied the benefits of prevention measures including counselling on infant feeding options