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Millions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes using WHO-recommended standardised regimens. Recent WHO guidelines recommend a boosted protease inhibitor plus raltegravir as an alternative second-line combination. We assessed whether this treatment option offers any advantage over the standard protease inhibitor plus two nucleoside reverse-transcriptase inhibitors (NRTIs) second-line combination after 144 weeks of follow-up in typical programme settings. We analysed the 144-week outcomes at the completion of the EARNEST trial, a randomised controlled trial done in HIV-infected adults or adolescents in 14 sites in five sub-Saharan African countries (Uganda, Zimbabwe, Malawi, Kenya, Zambia). Participants were those who were no longer responding to non-NRTI-based first-line ART, as assessed with WHO criteria, confirmed by viral-load testing. Participants were randomly assigned to receive a ritonavir-boosted protease inhibitor (lopinavir 400 mg with ritonavir 100 mg, twice per day) plus two or three clinician-selected NRTIs (protease inhibitor plus NRTI group), protease inhibitor plus raltegravir (400 mg twice per day; protease inhibitor plus raltegravir group), or protease inhibitor monotherapy (plus raltegravir induction for first 12 weeks, re-intensified to combination therapy after week 96; protease inhibitor monotherapy group). Randomisation was by computer-generated randomisation sequence, with variable block size. The primary outcome was viral load of less than 400 copies per mL at week 144, for which we assessed non-inferiority with a one-sided α of 0·025, and superiority with a two-sided α of 0·025. The EARNEST trial is registered with ISRCTN, number 37737787. Between April 12, 2010, and April 29, 2011, 1837 patients were screened for eligibility, of whom 1277 patients were randomly assigned to an intervention group. In the primary (complete-case) analysis at 144 weeks, 317 (86%) of 367 in the protease inhibitor plus NRTI group had viral loads of less than 400 copies per mL compared with 312 (81%) of 383 in the protease inhibitor plus raltegravir group (p=0·07; lower 95% confidence limit for difference 10·2% vs specified non-inferiority margin 10%). In the protease inhibitor monotherapy group, 292 (78%) of 375 had viral loads of less than 400 copies per mL; p=0·003 versus the protease inhibitor plus NRTI group at 144 weeks. There was no difference between groups in serious adverse events, grade 3 or 4 adverse events (total or ART-related), or events that resulted in treatment modification. Protease inhibitor plus raltegravir offered no advantage over protease inhibitor plus NRTI in virological efficacy or safety. In the primary analysis, protease inhibitor plus raltegravir did not meet non-inferiority criteria. A regimen of protease inhibitor with NRTIs remains the best standardised second-line regimen for use in programmes in resource-limited settings. European and Developing Countries Clinical Trials Partnership (EDCTP), UK Medical Research Council, Instituto de Salud Carlos III, Irish Aid, Swedish International Development Cooperation Agency, Instituto Superiore di Sanita, Merck, ViiV Healthcare, WHO.

Temperature increases due to climatic changes have been increasingly recognized as posing significant public health challenges, with wide-ranging socio-economic implications. This scoping review examines the relationship between high temperatures and violence against women (VAW) globally. Nine studies from both high-income and low- and middle-income countries were included in this review. The findings suggest an overall positive association between high temperatures and rates of VAW. Theoretical frameworks, including the temperature–aggression hypothesis and routine activity theory, offer insights into the mechanisms driving this relationship. Key risk factors such as socioeconomic status, urban heat island effects, rurality, patriarchal norms, and alcohol consumption were considered to be risk factors affecting rates of VAW. Despite growing evidence, research gaps persist, particularly in regions with high rates of VAW and in the form of qualitative studies that capture women’s lived experiences. The positive associations between temperature and VAW underscore the urgency of integrating gender-sensitive strategies into climate adaptation policies to mitigate the compounding risks of climate change and gender-based violence.

Preeclampsia (PE) is a significant obstetric complication associated with adverse maternal and fetal outcomes. Zambia, like several Sub-Saharan African nations, experiences a high prevalence of pregnancy-related hypertension, with PE being a major contributor to maternal and foetal mortality. This study aimed to identify the factors associated with the development of PE. We conducted a cross-sectional study at Livingstone University Teaching Hospital in Zambia (LUTH). PE was defined as new-onset hypertension with systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg occurring after 20 weeks of gestation, accompanied by proteinuria with dipstick reading of 1 + . Data from patients' most recent hospital visits was collected by trained research assistants using medical record abstraction. A total of 1018 participants were included. Demographic, clinical, and haematological parameters were analysed. We conducted both descriptive and inferential analyses using Stata version 17. Univariable and multivariable logistic regression were employed to investigate factors associated with PE. The median age of participants was 27 years (IQR: 21-33). The prevalence of PE was 12.2% (n = 124). Among the 17.7% (n = 172) of participants who were employed, 19.1% (n = 33) had PE. Factors positively associated with PE included increasing age (Adjusted Odds Ratio [AOR]: 1.07, 95% Confidence Interval [CI]: 1.02-1.12, p = 0.002), a previous history of PE (AOR: 30.8, 95% CI: 8.7-108.6, p < 0.001), and a family history of PE (AOR: 9.97, 95% CI: 2.53-39.27, p = 0.001). Conversely, a unit (week) increase in gestational age was negatively associated with PE (AOR: 0.89, 95% CI: 0.83-0.97, p = 0.007). This study identifies maternal age, family history, and prior obstetric history as key associated factors for PE, emphasizing the need for targeted screening and early intervention. Enhanced prenatal care, including routine risk assessments, patient education, and regular monitoring through blood pressure checks, urine protein testing, and fetal growth assessments, is cardinal for early detection and effective management of high-risk individuals.

WHO 2013 guidelines recommend universal treatment for HIV-infected children younger than 5 years. No paediatric trials have compared nucleoside reverse-transcriptase inhibitors (NRTIs) in first-line antiretroviral therapy (ART) in Africa, where most HIV-infected children live. We aimed to compare stavudine, zidovudine, or abacavir as dual or triple fixed-dose-combination paediatric tablets with lamivudine and nevirapine or efavirenz. In this open-label, parallel-group, randomised trial (CHAPAS-3), we enrolled children from one centre in Zambia and three in Uganda who were previously untreated (ART naive) or on stavudine for more than 2 years with viral load less than 50 copies per mL (ART experienced). Computer-generated randomisation tables were incorporated securely within the database. The primary endpoint was grade 2–4 clinical or grade 3/4 laboratory adverse events. Analysis was intention to treat. This trial is registered with the ISRCTN Registry number, 69078957. Between Nov 8, 2010, and Dec 28, 2011, 480 children were randomised: 156 to stavudine, 159 to zidovudine, and 165 to abacavir. After two were excluded due to randomisation error, 156 children were analysed in the stavudine group, 158 in the zidovudine group, and 164 in the abacavir group, and followed for median 2·3 years (5% lost to follow-up). 365 (76%) were ART naive (median age 2·6 years vs 6·2 years in ART experienced). 917 grade 2–4 clinical or grade 3/4 laboratory adverse events (835 clinical [634 grade 2]; 40 laboratory) occurred in 104 (67%) children on stavudine, 103 (65%) on zidovudine, and 105 (64%), on abacavir (p=0·63; zidovudine vs stavudine: hazard ratio [HR] 0·99 [95% CI 0·75–1·29]; abacavir vs stavudine: HR 0·88 [0·67–1·15]). At 48 weeks, 98 (85%), 81 (80%) and 95 (81%) ART-naive children in the stavudine, zidovudine, and abacavir groups, respectively, had viral load less than 400 copies per mL (p=0·58); most ART-experienced children maintained suppression (p=1·00). All NRTIs had low toxicity and good clinical, immunological, and virological responses. Clinical and subclinical lipodystrophy was not noted in those younger than 5 years and anaemia was no more frequent with zidovudine than with the other drugs. Absence of hypersensitivity reactions, superior resistance profile and once-daily dosing favours abacavir for African children, supporting WHO 2013 guidelines. European Developing Countries Clinical Trials Partnership.

Abstract Objective Immune activation is associated with morbidity and mortality during human immunodeficiency virus (HIV) infection, despite receipt of antiretroviral therapy (ART). We investigated whether microbial translocation drives immune activation in HIV-infected Ugandan children. Methods Nineteen markers of immune activation and inflammation were measured over 96 weeks in HIV-infected Ugandan children in the CHAPAS-3 Trial and HIV-uninfected age-matched controls. Microbial translocation was assessed using molecular techniques, including next-generation sequencing. Results Of 249 children included, 142 were infected with HIV; of these, 120 were ART naive, with a median age of 2.8 years (interquartile range [IQR], 1.7–4.0 years) and a median baseline CD4+ T-cell percentage of 20% (IQR, 14%–24%), and 22 were ART experienced, with a median age of 6.5 years (IQR, 5.9–9.2 years) and a median baseline CD4+ T-cell percentage of 35% (IQR, 31%–39%). The control group comprised 107 children without HIV infection. The median increase in the CD4+ T-cell percentage was 17 percentage points (IQR, 12–22 percentage points) at week 96 among ART-naive children, and the viral load was <100 copies/mL in 76% of ART-naive children and 91% of ART-experienced children. Immune activation decreased with ART use. Children could be divided on the basis of immune activation markers into the following 3 clusters: in cluster 1, the majority of children were HIV uninfected; cluster 2 comprised a mix of HIV-uninfected children and HIV-infected ART-naive or ART-experienced children; and in cluster 3, the majority were ART naive. Immune activation was low in cluster 1, decreased in cluster 3, and persisted in cluster 2. Blood microbial DNA levels were negative or very low across groups, with no difference between clusters except for Enterobacteriaceae organisms (the level was higher in cluster 1; P < .0001). Conclusion Immune activation decreased with ART use, with marker clustering indicating different activation patterns according to HIV and ART status. Levels of bacterial DNA in blood were low regardless of HIV status, ART status, and immune activation status. Microbial translocation did not drive immune activation in this setting. Clinical Trials Registration ISRCTN69078957. We found no evidence of an association between microbial translocation and immune activation in Ugandan human immunodeficiency virus (HIV)–infected children over time during receipt of antiretroviral therapy or in comparison to HIV-uninfected controls. In this setting, other factors may be driving immune activation in both infected and uninfected children.

This dissertation focuses on the protection and promotion of the socio-economic rights of children with disabilities in South Africa. Socio-economic rights aim to ensure that material inequalities that are experienced by children with disabilities are addressed in a manner that acknowledges their dignity, freedom and equality. Particular attention is paid to the right to basic education and right to social services. The dissertation highlights how the protection and promotion of these rights has an impact on children with disabilities’ physical and mental development.An extensive desktop research investigated the manner in which obligations placed on the state are being implemented. Selected international and regional instruments, as well as the Constitution of the Republic of South Africa and relevant national legislation are examined in so far as they relate to the protection of children with disabilities. Thereafter, the implementation of these legally based obligations is discussed.The findings from the research show the existence of clearly expressed obligations in international and regional law, as well as commendable national legal frameworks that protect and promote the right to basic education and right to social services for children with disabilities. Despite this, children with disabilities still experience a number of discriminatory barriers that hinder their access to basic education and social services.The dissertation concludes that more needs to be done by way of state action to ensure better interpretation and implementation of international and regional law as well as national law. Recommendations are given in this regard. Interpretation and implementation should be strengthen to ensure that children with disabilities benefit fully from access to basic education and social services.

Abstract Objective : To compare effectiveness of different methods of monitoring intrapartum fetal heart rate. Design : Prospective randomised controlled trial. Setting : Referral maternity hospital, Harare,Zimbabwe. Subjects : 1255 women who were 37 weeks or more pregnant with singleton cephalic presentation and normal fetal heart rate before entry into study. Interventions : Intermittent monitoring of fetal heart rate by electronic monitoring, Doppler ultrasound, use of Pinard stethoscope by a research midwife, or routine use of Pinard stethoscope by attending midwife. Main outcome measures - Abnormal fetal heart rate patterns, need for operative delivery for fetal distress, neonatal mortality, Apgar scores, admission to neonatal unit, neonatal seizures, and hypoxic ischaemic encephalopathy. Results : Abnormalities in fetal heart rate were detected in 54% (172/318) of the electronic monitoring group, 32% (100/312) of the ultrasonography group, 15% (47/310) of the Pinard stethoscope group, and 9% (28/315) of the routine monitoring group. Caesarean sections were performed for 28% (89), 24% (76), 10% (32), and 15% (46) of the four groups respectively. Neonatal outcome was best in the ultrasonography group: hypoxic ischaemic encephalopathy occurred in two, one, seven, and 10 cases in the four groups respectively; neonatal seizures occurred only in the last two groups (six and nine cases respectively); and deaths occurred in eight,two, five, and nine cases respectively. Conclusions : Abnormalities in fetal heart rate were more reliably detected by Doppler ultrasonography than with Pinard stethoscope, and its use resulted in good perinatal outcome. The use ofrelatively cheap ultrasound monitors should be further evaluated and promoted in obstetric units caring for high risk pregnancies in developing countries with scarce resources.

The purpose of this study was to provide a better understanding of food security problems in Zambia from a rural household perspective. The study specifically addresses itself to how households meet target consumption levels on a yearly basis in the face of fluctuating production, prices and household incomes. The dissertation includes a descriptive analysis of the food grain production and distribution system in Zambia, followed by an investigation of rural households' food production and disposal behavior, including the utilization of on-farm storage facilities. The data used in the analysis were collected by the author from both primary and secondary sources. Primary data were collected from a sample of 132 rural households in Mumbwa District, between July and November 1985. Secondary data were collected from published and unpublished reports from a number of government departments, parastatal organizations and international agencies. Maize is the major food grain produced in Zambia and is also the main staple food commodity. Besides being the most important food item among the rural households, it is also the main source of income. Over 60 percent of the maize produced is used for home consumption, the rest is sold to the monopsonistic grain marketing board or cooperative unions that operate in each Zambian province. The government policy of pan-territorial and pan-seasonal pricing has made it unprofitable to store food crops on farms and has encouraged farmers to sell the grain following the harvest. This has made rural food deficit households more vulnerable to food insecurity. The public sector grain marketing system operates to move grain from rural areas to urban centers but have largely neglected the backflow of grain. Grain deficit households in rural areas mainly depend on other rural households for supplemental food supplies. The investigations also revealed that households undertake various actions to guard against poor food harvests. These include storing more grain than what is required in a single season, undertaking other agricultural activities that can raise income, such as growing vegetables and other cash crops, practicing mixed cropping or selling animals, beer and fish. Beer selling was particularly common among the low income households.