ABSTRACT
BACKGROUND: In resource-limited settings, holding regimens such as lamivudine monotherapy (LAM) have been used to manage HIV-positive children failing combination antiretroviral therapy to mitigate the risk of drug resistance developing, while adherence barriers are addressed or when access to second- or third-line regimens is restricted. South African HIV treatment guidelines previously advocated the use of LAM to manage HIV-infected children with virological failure. However, the outcomes of patients on LAM compared with those who continued on a failing regimen have not been well described. Objectives. To investigate characteristics of a large cohort of children placed on LAM and their outcomes. Methods. This was a retrospective review of children with virological failure and the documented M184V drug resistance mutation who were placed on LAM v. a control group of children who continued on a failing regimen despite persistent virological failure. Virological and immunological outcomes of LAM were compared with those in patients who remained on a failing regimen. Results. A total of 179 children were included in the analysis, with 92 in the LAM group and 87 in the control group. The median (interquartile range (IQR)) age at baseline was 9.2 (5.4 - 12) years, the median CD4 count was 384 (184 - 622) cells/µL, and the median HIV viral load was 4.7 (IQR 3.7 - 5.3) log10. Twenty-two children (25.6%) in the LAM group and 15 (17.4%) in the control group experienced immunological deterioration. There was no statistical difference between the two groups with regard to overall time to immunological deterioration (log-rank p-value 0.4810). Conclusion. Given that a higher proportion of children in the LAM group experienced immunological failure, the LAM strategy may be a useful short-term one but should be restricted to children with limited treatment options. Managing children with virological failure will continue to be a challenge until improved adherence strategies are available.
Subject(s)
Anti-HIV Agents , HIV Infections , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , Child , Child, Preschool , HIV Infections/drug therapy , Humans , Lamivudine/therapeutic use , Public Sector , South Africa , Treatment Failure , Viral LoadABSTRACT
We describe a case of prolonged SARS-CoV-2 RNA shedding in an HIV-negative 21-year-old man recovering from abdominal and thoracic trauma. Nasopharyngeal (NP) swabs collected at 12 time points over a 95-day span all tested positive for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR). Genotyping revealed canonical beta-variant E484K and N501Y mutations at earlier time points. Human rhinovirus, coronavirus NL63 and respiratory syncytial virus B were detected at different time points by RT-PCR. Full blood analysis at time point 9 (day 82) showed leukopenia with lymphocytosis. The patient's NP swab tested negative for SARS-CoV-2 by RT-PCR 101 days after the first positive test. The prolonged duration of SARS-CoV-2 RNA shedding in the context of trauma presented here is unique and has important implications for COVID-19 diagnosis, management and policy guidelines.
Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Pneumothorax/physiopathology , SARS-CoV-2/isolation & purification , Genotype , Humans , Male , RNA, Viral/isolation & purification , SARS-CoV-2/genetics , Time Factors , Virus Shedding , Young AdultABSTRACT
We describe a case of prolonged SARS-CoV-2 RNA shedding in an HIV-negative 21-year-old man recovering from abdominal and thoracic trauma. Nasopharyngeal (NP) swabs collected at 12 time points over a 95-day span all tested positive for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR). Genotyping revealed canonical beta-variant E484K and N501Y mutations at earlier time points. Human rhinovirus, coronavirus NL63 and respiratory syncytial virus B were detected at different time points by RT-PCR. Full blood analysis at time point 9 (day 82) showed leukopenia with lymphocytosis. The patient's NP swab tested negative for SARS-CoV-2 by RT-PCR 101 days after the first positive test. The prolonged duration of SARS-CoV-2 RNA shedding in the context of trauma presented here is unique and has important implications for COVID-19 diagnosis, management and policy guidelines
Subject(s)
Humans , Male , Adult , Pneumothorax , COVID-19 Nucleic Acid Testing , SARS-CoV-2 , COVID-19ABSTRACT
BACKGROUND: Large cohorts of HIV-1 perinatally infected children with long-term follow-up in developing countries are limited. OBJECTIVES: To explore rates and predictors of virological failure in a paediatric cohort. METHODS: A 10-year retrospective study was conducted from January 2004 to December 2013 to determine the incidence of and factors associated with virological failure among 1 659 HIV perinatally infected children in a public sector setting in South Africa (SA). Children aged <17 years who initiated first-line antiretroviral therapy between 1 January 2004 and 31 December 2013 and had at least 5 years of HIV viral load measurements were eligible. RESULTS: The 1 659 children contributed 7 075 person-years of follow-up (PYFU). In the initial cohort of 2 024 children, 51.0% were male and 62.0% were aged <5 years. The incidence of virological failure was 18.7 per 100 PYFU. Virological failure was associated with male gender, death of the mother, concurrent tuberculosis treatment and World Health Organization stage IV disease. Of the 320 HIV isolates successfully amplified, 249 (77.8%) had drug resistance mutations. CONCLUSIONS: We observed high rates of virological failure and emergence of HIV drug resistance mutations. Despite gains made by SA in the treatment of HIV, such results challenge the country's ability to meet global targets of 90% viral suppression by 2020.
