Clinical indicators of Pneumocystis jiroveci pneumonia (PCP) in South African children infected with human immunodeficiency virus

Includes bibliographical references (leaves 53-60).Pneumocystis pneumonia (PCP) is an important cause of morbidity and mortality amongst HIV-infected children in Africa. Definitive diagnostic resources for PCP in Africa are limited due to their expense and technical difficulty, however recognising and treating children at risk is essential. As management decisions for children with pneumonia are made primarily on a clinical basis in many African regions, it is important to attempt to define a valid clinical diagnostic technique for PCP that could be used by clinicians to determine the use of correct empirical antibiotic therapy. The objectives of this study were to identify clinical features (associated with PCP in HIV-infected children hospitalised with pneumonia, to determine the combination of features that best predicts PCP in these children, and to calculate the diagnostic accuracy of these features. This study was a re-analysis of a database of a prospective study. Consecutive children below ten years of age, with a primary diagnosis of pneumonia or severe pneumonia, and who were known to be HIV-infected or were suspected of having HIV infection, were included prospectively over a 12 month period. Clinical data and diagnostic testing for PCP were obtained on admission. Bi­ and multivariate analysis of associations of the clinical variables with PCP were performed using logistic regression, to identify the combination of variables that best predicted PCP. The diagnostic accuracy of the best predicted features were calculated

Antiretroviral treatment outcomes amongst older adults in a large multicentre cohort in South Africa

Introduction Increasing numbers of patients are starting antiretroviral treatment (ART) at advanced age or reaching advanced age while on ART. We compared baseline characteristics and ART outcomes of older adults (aged ≥55 years) vs. younger adults (aged 25-54 years) in routine care settings in South Africa. METHODS: A multicentre cohort study of ART-naïve adults starting ART at 89 public sector facilities was conducted. Mortality, loss to follow-up (LTFU), immunological and virological outcomes until five years of ART were compared using competing-risks regression, generalised estimating equations and mixed-effects models. RESULTS: 4065 older adults and 86,006 younger adults were included. There were more men amongst older adults; 44.7% vs. 33.4%; RR = 1.34 (95% CI: 1.29-1.39). Mortality after starting ART was substantially higher amongst older adults, adjusted sub-hazard ratio (asHR) = 1.44 over 5 years (95% CI: 1.26-1.64), particularly for the period 7-60 months of treatment, asHR = 1.73 (95% CI: 1.44-2.10). LTFU was lower in older adults, asHR = 0.87 (95% CI: 0.78-0.97). Achievement of virological suppression was greater in older adults, adjusted odds ratio = 1.42 (95% CI: 1.23-1.64). The probabilities of viral rebound and confirmed virological failure were both lower in older adults, adjusted hazard ratios = 0.69 (95% CI: 0.56-0.85) and 0.64 (95% CI: 0.47-0.89), respectively. The rate of CD4 cell recovery (amongst patients with continuous viral suppression) was 25 cells/6 months of ART (95% CI: 17.3-33.2) lower in older adults. CONCLUSIONS: Although older adults had better virological outcomes and reduced LTFU, their higher mortality and slower immunological recovery warrant consideration of age-specific ART initiation criteria and management strategies

Adolescent and young pregnant women at increased risk of mother-to-child transmission of HIV and poorer maternal and infant health outcomes: A cohort study at public facilities in the Nelson Mandela Bay Metropolitan district, Eastern Cape, South Africa

BACKGROUND: South Africa (SA) has the highest burden of childhood HIV infection globally, and has high rates of adolescent and youth pregnancy OBJECTIVE: To explore risks associated with pregnancy in young HIV-infected women, we compared mother-to-child transmission (MTCT) of HIV and maternal and infant health outcomes according to maternal age categories METHODS: A cohort of HIV-positive pregnant women and their infants were followed up at three sentinel surveillance facilities in the Nelson Mandela Bay Metropolitan (NMBM) district, Eastern Cape Province, SA. Young women were defined as 24 years as the comparison group RESULTS: Of 956 mothers, 312 (32.6%) were young women; of these, 65 (20.8%) were adolescents. The proportion of young pregnant women increased by 24% between 2009/10 and 2011/12 (from 28.3% to 35.1%). Young women had an increased risk of being unaware of their HIV status when booking (adjusted risk ratio (aRR) 1.37; 95% confidence interval (CI) 1.21 - 1.54), a reduced rate of antenatal antiretroviral therapy (ART) uptake (adjusted hazard ratio 0.46; 95% CI 0.31 - 0.67), reduced early infant HIV diagnosis (aRR 0.94; 95% CI 0.94 - 0.94), and increased MTCT (aRR 3.07; 95% CI 1.18 - 7.96; adjusted for ART use). Of all vertical transmissions, 56% occurred among young women. Additionally, adolescents had increased risks of first presentation during labour (aRR 3.78; 95% CI 1.06 - 13.4); maternal mortality (aRR 35.1; 95% CI 2.89 - 426) and stillbirth (aRR 3.33; 95% CI 1.53 - 7.25 CONCLUSION: An increasing proportion of pregnant HIV-positive women in NMBM were young, and they had increased MTCT and poorer maternal and infant outcomes than older women. Interventions targeting young women are increasingly needed to reduce pregnancy, HIV infection and MTCT and improve maternal and infant outcomes if SA is to attain its Millennium Development Goal

Prevalence and trends of advanced HIV disease among antiretroviral therapy-naïve and antiretroviral therapy-experienced patients in South Africa between 2010-2021: A systematic review and meta-analysis

BACKGROUND: Despite the significant progress made in South Africa in getting millions of individuals living with HIV into care, many patients still present or re-enter care with Advanced HIV Disease (AHD). We aimed to estimate the prevalence of AHD among ART-naive and ART-experienced patients in South Africa using studies published between January 2010 and May 2022. METHODS: We searched for relevant data on PubMed, CINAHL, Scopus and other sources, with a geographical filters limited to South Africa, up to May 31, 2022. Two reviewers conducted all screening, eligibility assessment, data extraction, and critical appraisal. We synthesized the data using the inverse-variance heterogeneity model and Freeman-Tukey transformation. We assessed heterogeneity using the I RESULTS: We identified 2,496 records, of which 53 met the eligibility criteria, involving 11,545,460 individuals. The pooled prevalence of AHD among ART-naive and ART-experienced patients was 43.45% (95% CI 40.1-46.8%, n = 53 studies) and 58.6% (95% CI 55.7 to 61.5%, n = 2) respectively. The time trend analysis showed a decline of 2% in the prevalence of AHD among ART-naive patients per year. However, given the high heterogeneity between studies, the pooled prevalence should be interpreted with caution. CONCLUSION: Despite HIV\u27s evolution to a chronic disease, our findings show that the burden of AHD remains high among both ART-naive and ART-experienced patients in South Africa. This emphasizes the importance of regular measurement of CD4 cell count as an essential component of HIV care. In addition, providing innovative adherence support and interventions to retain ART patients in effective care is a crucial priority for those on ART

Outcomes of second-line antiretroviral therapy among children living with HIV: a global cohort analysis.

INTRODUCTION Limited data describe outcomes on second-line antiretroviral therapy (ART) among children globally. Our objective was to contribute data on outcomes among children living with HIV after initiation of second-line ART in the context of routine care within a large global cohort collaboration. METHODS Patient-level data from 1993 through 2015 from 11 paediatric HIV cohorts were pooled. Characteristics at switch and through two years of follow-up were summarized for children who switched to second-line ART after starting a standard first-line regimen in North America, Latin America, Europe, Asia, Southern Africa (South Africa & Botswana) and the rest of sub-Saharan Africa (SSA). Cumulative incidences of mortality and loss to follow-up (LTFU) were estimated using a competing risks framework. RESULTS Of the 85,389 children on first-line ART, 3,555 (4%) switched to second-line after a median of 2.8 years on ART (IQR: 1.6, 4.7); 69% were from Southern Africa or SSA and 86% of second-line regimens were protease inhibitor-based. At switch, median age was 8.4 years and 50% had a prior AIDS diagnosis. Median follow-up after switch to second-line ranged from 1.8 years in SSA to 5.3 years in North America. Median CD4 counts at switch to second-line ranged from 235 cells/mm3 in SSA to 828 cells/mm3 in North America. Improvements in CD4 counts were observed over two years of follow-up, particularly in regions with lower CD4 counts at second-line switch. Improvements in weight-for-age z-scores were not observed during follow-up. Cumulative incidence of LTFU at two years was <5% in all regions except SSA (7.1%) and Southern Africa (7.4%). Risk of mortality was <3% at two years of follow-up in all regions, except Latin America (4.9%) and SSA (5.5%). CONCLUSIONS Children switched to second-line ART experience CD4 count increases as well as low to moderate rates of LTFU and mortality within two years after switch. Severe immune deficiency at time of switch in some settings suggests need for improved recognition and management of treatment failure in children

Adolescent and young pregnant women at increased risk of mother-to-child transmission of HIV and poorer maternal and infant health outcomes: A cohort study at public facilities in the Nelson Mandela Bay Metropolitan district, Eastern Cape, South Africa

Background. South Africa (SA) has the highest burden of childhood HIV infection globally, and has high rates of adolescent and youth pregnancy.Objective. To explore risks associated with pregnancy in young HIV-infected women, we compared mother-to-child transmission (MTCT) of HIV and maternal and infant health outcomes according to maternal age categories.Methods. A cohort of HIV-positive pregnant women and their infants were followed up at three sentinel surveillance facilities in the Nelson Mandela Bay Metropolitan (NMBM) district, Eastern Cape Province, SA. Young women were defined as ≤24 years old and adolescents as ≤19 years. The effect of younger maternal age categories on MTCT and maternal and child health outcomes was assessed using log-binomial and Cox regression controlling for confounding, using women aged &gt;24 years as the comparison group.Results. Of 956 mothers, 312 (32.6%) were young women; of these, 65 (20.8%) were adolescents. The proportion of young pregnant women increased by 24% between 2009/10 and 2011/12 (from 28.3% to 35.1%). Young women had an increased risk of being unaware of their HIV status when booking (adjusted risk ratio (aRR) 1.37; 95% confidence interval (CI) 1.21 - 1.54), a reduced rate of antenatal antiretroviral therapy (ART) uptake (adjusted hazard ratio 0.46; 95% CI 0.31 - 0.67), reduced early infant HIV diagnosis (aRR 0.94; 95% CI 0.94 - 0.94), and increased MTCT (aRR 3.07; 95% CI 1.18 - 7.96; adjusted for ART use). Of all vertical transmissions, 56% occurred among young women. Additionally, adolescents had increased risks of first presentation during labour (aRR 3.78; 95% CI 1.06 - 13.4); maternal mortality (aRR 35.1; 95% CI 2.89 - 426) and stillbirth (aRR 3.33; 95% CI 1.53 - 7.25).Conclusion. An increasing proportion of pregnant HIV-positive women in NMBM were young, and they had increased MTCT and poorer maternal and infant outcomes than older women. Interventions targeting young women are increasingly needed to reduce pregnancy, HIV infection and MTCT and improve maternal and infant outcomes if SA is to attain its Millennium Development Goals

A mechanistic model for long-term immunological outcomes in South African HIV-infected children and adults receiving ART.

Long-term effects of the growing population of HIV-treated people in Southern Africa on individuals and the public health sector at large are not yet understood. This study proposes a novel 'ratio' model that relates CD4+ T-cell counts of HIV-infected individuals to the CD4+ count reference values from healthy populations. We use mixed-effects regression to fit the model to data from 1616 children (median age 4.3 years at ART initiation) and 14,542 adults (median age 36 years at ART initiation). We found that the scaled carrying capacity, maximum CD4+ count relative to an HIV-negative individual of similar age, and baseline scaled CD4+ counts were closer to healthy values in children than in adults. Post-ART initiation, CD4+ growth rate was inversely correlated with baseline CD4+ T-cell counts, and consequently higher in adults than children. Our results highlight the impacts of age on dynamics of the immune system of healthy and HIV-infected individuals

Increased vulnerability of rural children on antiretroviral therapy attending public health facilities in South Africa: a retrospective cohort study

BACKGROUND: A large proportion of the 340,000 HIV-positive children in South Africa live in rural areas, yet there is little sub-Saharan data comparing rural paediatric antiretroviral therapy (ART) programme outcomes with urban facilities. We compared clinical, immunological and virological outcomes between children at seven rural and 37 urban facilities across four provinces in South Africa. METHODS: We conducted a retrospective cohort study of routine data of children enrolled on ART between November 2003 and March 2008 in three settings, namely: urban residence and facility attendance (urban group); rural residence and facility attendance (rural group); and rural residents attending urban facilities (rural/urban group). Outcome measures were: death, loss to follow up (LTFU), virological suppression, and changes in CD4 percentage and weight-for-age-z (WAZ) scores. Kaplan-Meier estimates, logrank tests, multivariable Cox regression and generalized estimating equation models were used to compare outcomes between groups. RESULTS: In total, 2332 ART-naive children were included, (1727, 228 and 377 children in the urban, rural and rural/urban groups, respectively). At presentation, rural group children were older (6.7 vs. 5.6 and 5.8 years), had lower CD4 cell percentages (10.0% vs. 12.8% and 12.7%), lower WAZ scores (-2.06 vs. -1.46 and -1.41) and higher proportions with severe underweight (26% vs.15% and 15%) compared with the urban and rural/urban groups, respectively. Mortality was significantly higher in the rural group and LTFU significantly increased in the rural/urban group. After 24 months of ART, mortality probabilities were 3.4% (CI: 2.4-4.8%), 7.7% (CI: 4.5-13.0%) and 3.1% (CI: 1.7-5.6%) p = 0.0137; LTFU probabilities were 11.5% (CI: 9.3-14.0%), 8.8% (CI: 4.5-16.9%) and 16.6% (CI: 12.4-22.6%), p = 0.0028 in the urban, rural and rural/urban groups, respectively. The rural group had an increased adjusted mortality probability, adjusted hazards ratio 2.41 (CI: 1.25-4.67) and the rural/urban group had an increased adjusted LTFU probability, aHR 2.85 (CI: 1.41-5.79). The rural/urban group had a decreased adjusted probability of virological suppression compared with the urban group at any timepoint on treatment, adjusted odds ratio 0.67 (CI: 0.48-0.93). CONCLUSIONS: Rural HIV-positive children are a vulnerable group, exhibiting delayed access to ART and an increased risk of poor outcomes while on ART. Expansion of rural paediatric ART programmes, with future research exploring improvements to rural health system effectiveness, is required