Safety, adherence, and HIV-1 seroconversion among women using the dapivirine vaginal ring (DREAM): an open-label, extension study.

BACKGROUND: The Ring Study, a phase 3 trial in 1959 sexually active women (randomised 2:1), showed a favourable safety profile and a 31% HIV-1 infection risk reduction for a vaginal ring containing 25 mg of dapivirine, compared with a placebo ring. We report here the DREAM study, which aimed to evaluate safety, adherence, and HIV-1 incidence in those using the dapivirine vaginal ring (DVR) in open-label use. METHODS: The DREAM study is an open-label extension of The Ring Study, done at five research centres in South Africa and one research centre in Uganda. Former participants from The Ring Study, who remained HIV-negative and who did not discontinue the study due to an adverse event or safety concern that was considered to be related to the investigational product, were eligible. Women who were pregnant, planning to become pregnant, or breastfeeding at screening for DREAM were excluded. All participants received the DVR for insertion at the enrolment visit. Participants attended a 1-month follow-up visit and could either proceed with visits once every 3 months or attend monthly visits up to month 3 and then continue with visits once every 3 months. At each visit, HIV testing and safety evaluations were done, and residual dapivirine measured in used rings (approximately 4 mg is released from the DVR over 28 days of consistent use). HIV-1 incidence was compared descriptively with the simulated incidence rate obtained from bootstrap sampling of participants in the placebo group of The Ring Study, matched for research centre, age, and presence of sexually transmitted infections at enrolment. This study is registered with ClinicalTrials.gov, NCT02862171. FINDINGS: Between July 12, 2016, and Jan 11, 2019, 1034 former participants from The Ring Study were screened, 941 were enrolled and 848 completed the trial. 616 (65·5%) of 941 participants reported treatment-emergent adverse events. Of these, six (0·6%) had events considered to be treatment-related. No treatment-related serious adverse events were reported. Measurements of monthly ring residual amounts in participants enrolled in both trials showed consistently lower mean values in DREAM than in The Ring Study. Arithmetic mean ring residual amounts of participants in The Ring Study DVR group who enrolled in DREAM were 0·25 mg lower (95% CI 0·03-0·47; p=0·027) than the mean ring residual amounts of these participants in The Ring Study. 18 (1·9%) HIV-1 infections were confirmed during DVR use, resulting in an incidence of 1·8 (95% CI 1·1-2·6) per 100 person-years, 62% lower than the simulated placebo rate. INTERPRETATION: Although efficacy estimation is limited by the absence of a placebo group, the observed low HIV-1 incidence and improved adherence observed in DREAM support the hypothesis that increased efficacy due to improved adherence occurs when women know the demonstrated safety and efficacy of the DVR. The feasibility of a visit schedule of once every 3 months was shown, indicating that the DVR can be used in a real-world situation in usual clinical practice. FUNDING: The Ministry of Foreign Affairs (MFA) Denmark, Flanders MFA, Irish Aid, Dutch MFA, UK Aid from the UK Government's Foreign, Commonwealth and Development Office, and the US President's Emergency Plan for AIDS Relief through the US Agency for International Development.

Health and educational achievement of school-aged children: The impact of anaemia and iron status on learning.

BACKGROUND: Anaemia is a common blood disorder in children and is known to cause complications such as lethargy and stress on bodily organs. Children from disadvantaged communities often fail to achieve their age-related potential with iron deficiency anaemia stated as a risk factor through causing inattentiveness and learning problems. Limited evidence exists for the adverse effects of iron deficiency anaemia on the developing child's brain from South African studies. AIM: The objective of this study was to determine the local prevalence of anaemia and iron deficiency and to examine their association with psychomotor development and school performance in school-aged children. SETTING: This study was conducted in a peri-urban disadvantaged community from KwaZulu-Natal, South Africa. METHODS: Children aged 6 to 8 years from KwaZulu-Natal were enrolled (n = 184). Three parameters of assessment were used: clinical data, biochemical data (haemoglobin levels and iron studies) and school performance (interviews with caregivers, teachers and the children). Anaemia presence and iron deficiency were the hypothesised mediating variables through which growth, development and school performance were influenced. RESULTS: A high point prevalence of anaemia (23.4%), iron deficiency anaemia (4.9%) and helminth infection (27.1%) was identified. Impaired cognitive assessment scores (20.7%) were prevalent in the children sampled. Behavioural problems (4.3%), poor memory function (4.3%) and impaired attention (1.1%) were of low prevalence. Anaemia and iron deficiency were both associated with impaired fine motor skills (p < 0.05). Anaemia was significantly associated with low cognitive scores (p = 0.01). Neither anaemia, iron status nor helminth infection significantly predicted school performance in the children sampled. CONCLUSIONS: The point prevalence of anaemia and iron deficiency among the sampled children was higher than the national prevalence. The sample size was however inadequate for drawing statistical conclusions about psychomotor development and school performance because of the low prevalence of the different outcomes that were examined. Practical challenges faced in conducting this investigation in rural South African schools were discussed.

Health and educational achievement of school-aged children: The impact of anaemia and iron status on learning

Background: Anaemia is a common blood disorder in children and is known to cause complications such as lethargy and stress on bodily organs. Children from disadvantaged communities often fail to achieve their age-related potential with iron deficiency anaemia stated as a risk factor through causing inattentiveness and learning problems. Limited evidence exists for the adverse effects of iron deficiency anaemia on the developing child's brain from South African studies. Aim: The objective of this study was to determine the local prevalence of anaemia and iron deficiency and to examine their association with psychomotor development and school performance in school-aged children. Setting: This study was conducted in a peri-urban disadvantaged community from KwaZulu-Natal, South Africa. Methods: Children aged 6 to 8 years from KwaZulu-Natal were enrolled (n = 184). Three parameters of assessment were used: clinical data, biochemical data (haemoglobin levels and iron studies) and school performance (interviews with caregivers, teachers and the children). Anaemia presence and iron deficiency were the hypothesised mediating variables through which growth, development and school performance were influenced. Results: A high point prevalence of anaemia (23.4%), iron deficiency anaemia (4.9%) and helminth infection (27.1%) was identified. Impaired cognitive assessment scores (20.7%) were prevalent in the children sampled. Behavioural problems (4.3%), poor memory function (4.3%) and impaired attention (1.1%) were of low prevalence. Anaemia and iron deficiency were both associated with impaired fine motor skills (p < 0.05). Anaemia was significantly associated with low cognitive scores (p = 0.01). Neither anaemia, iron status nor helminth infection significantly predicted school performance in the children sampled. Conclusions: The point prevalence of anaemia and iron deficiency among the sampled children was higher than the national prevalence. The sample size was however inadequate for drawing statistical conclusions about psychomotor development and school performance because of the low prevalence of the different outcomes that were examined. Practical challenges faced in conducting this investigation in rural South African schools were discussed

Anaemia control and the interpretation of biochemical tests for iron status in children.

BACKGROUND: Anaemia is one of the world's most prevalent child health problems. Its control in Africa and other developing nations has been hindered by uncertainty regarding its cause. Anaemia control has been particularly problematic in regions where the non-iron deficiency causes of anaemia, are projected to be substantial. The implementation of effective interventions to reduce the anaemia prevalence, requires improved documentation on iron status and other causes of anaemia for target populations. METHODS: This cross-sectional study enrolled n = 184 children, aged 6-8 years from Kwazulu-Natal, South Africa. Tests of haemoglobin, serum ferritin, soluble transferrin receptor and C-reactive protein were performed. These conventional measures of iron status were used to calculate body iron and to categorize the children into different groups of anaemia profiles. RESULTS: Anaemia prevalence was high, 43/184 (23.4%). Iron deficiency anaemia contributed 7/43 (16.3%) to the anaemia prevalence compared to non-iron deficiency anaemia 34/43 (79.1%) and mixed anaemia 2/43 (4.7%). In total 47/184 (25.5%) of the sampled children had either iron deficiency or anaemia. Information about the presence of inflammation was used to adjust serum ferritin concentrations, resulting in improved diagnosis of iron deficiency. CONCLUSION: Appropriate investigations for iron status and inflammation/infection screening, need to be integral in the evaluation of anaemia and its causes before anaemia control interventions are implemented. Interventions that target the multifactorial nature of anaemia in school-aged children need to be strengthened. Additionally, regular screening of anaemia in school-aged children from disadvantaged communities is recommended.