45 research outputs found
Predictive value of absolute CD4 cell count for disease progression in untreated HIV-1-infected children.
No full textOBJECTIVES: To describe the relationship between absolute CD4 cell count and the short-term risk of disease progression in HIV-1-infected children. DESIGN: A meta-analysis of individual longitudinal data on HIV-1-infected children enrolled in trials and cohort studies in Europe and the USA. METHODS: The risks of progression to death and AIDS (or death) within 12 months, in terms of age and the most recent CD4 cell count, were estimated using parametric survival models. The analysis was restricted to measurements before the start of antiretroviral therapy except zidovudine monotherapy. The values of the absolute CD4 cell count and percentage predicting selected levels of disease progression risk were determined from this and previous models. RESULTS: A total of 566 deaths was observed over 9128 person-years of follow-up, and 992 children progressed to AIDS or death over 7309 person-years of follow-up. In children older than 4 or 5 years, the estimated risk of disease progression increased sharply when the CD4 cell count fell below 200-300 cells/microl. As with other immunological markers, CD4 cell count was less prognostic in younger children. The CD4 cell count values predicting a 12-month risk of death of 2-5% and of AIDS of 5-10% were much more strongly influenced by age than equivalent CD4 cell percentage values. CONCLUSION: This study suggests it may be appropriate to extend CD4 cell count criteria for initiating antiretroviral therapy in HIV-1-infected adults to children as young as 4 or 5 years. Monitoring by CD4 cell count in younger children is problematical because age is a highly influential variable
Use of total lymphocyte count for informing when to start antiretroviral therapy in HIV-infected children: a meta-analysis of longitudinal data.
No full textBACKGROUND: Total lymphocyte count has been proposed as an alternative to the percentage of CD4+ T-cells to indicate when antiretroviral therapy should be started in children with HIV in resource-poor settings. We aimed to assess thresholds of total lymphocyte count at which antiretroviral therapy should be considered, and compared monitoring of total lymphocyte count with monitoring of CD4-cell percentage. METHODS: Longitudinal data on 3917 children with HIV infection were pooled from observational and randomised studies in Europe and the USA. The 12-month risks of death and AIDS by most recent total lymphocyte count and age were estimated by parametric survival models, based on measurements before antiretroviral therapy or during zidovudine monotherapy. Risks were derived and compared at thresholds of total lymphocyte count and CD4-cell percentage for starting antiretroviral therapy recommended in WHO 2003 guidelines. FINDINGS: Total lymphocyte count was a powerful predictor of the risk of disease progression despite a weak correlation with CD4-cell percentage (r=0.08-0.19 dependent on age). For children older than 2 years, the 12-month risk of death and AIDS increased sharply at values less than 1500-2000 cells per muL, with little trend at higher values. Younger children had higher risks and total lymphocyte count was less prognostic. Mortality risk was substantially higher at thresholds of total lymphocyte count recommended by WHO than at corresponding thresholds of CD4-cell percentage. When the markers were compared at the threshold values at which mortality risks were about equal, total lymphocyte count was as effective as CD4-cell percentage for identifying children before death, but resulted in an earlier start of antiretroviral therapy. INTERPRETATION: In this population, total lymphocyte count was a strong predictor of short-term disease progression, being only marginally less predictive than CD4-cell percentage. Confirmatory studies in resource-poor settings are needed to identify the most cost-effective markers to guide initiation of antiretroviral therapy
Current CD4 cell count and the short-term risk of AIDS and death before the availability of effective antiretroviral therapy in HIV-infected children and adults.
No full textBACKGROUND: Currently, there are no comparable estimates of the short-term risk of disease progression in the absence of effective antiretroviral therapy for human immunodeficiency virus (HIV)-infected adults and children. METHODS: A joint analysis of 2 large studies of children with vertically acquired HIV infection (the HIV Paediatric Prognostic Markers Collaborative Study) and adults with seroconversion (the CASCADE [Concerted Action on Sero-Conversion to AIDS and Death in Europe] collaboration) was conducted. Follow-up was censored at the end of 1995, before the introduction of combination antiretroviral therapy. The incidence rates of death and AIDS or death (AIDS/death) were estimated on the basis of age and current CD4 cell count. RESULTS: A total of 1260 deaths (over 20,500 person-years of follow-up) and 1894 initial AIDS events (over 17,200 person-years of follow-up) were observed among 6741 patients (3244 children [i.e., patients or = 5 years of age
Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection
Get PDFAlthough the pathogenesis of human immunodeficiency virus (HIV) infection and the general virologic and immunologic principles underlying the use of antiretroviral therapy are similar for all HIV-infected persons, there are unique considerations needed for HIV-infected infants, children, and adolescents, including; A acquisition of infection through perinatal exposure for many infected children, In utero, intrapartum, and/or postpartum neonatal exposure to zidovudine (ZDV) and other antiretroviral medications in most perinatally infected children, Requirement for use of HIV virologic tests to diagnose perinatal HIV infection in infants under age 15 to 18 months old, Age-specific differences in immunologic markers (i.e., CD4+ T cell count), Changes in pharmacokinetic parameters with age caused by the continuing development and maturation of organ systems involved in drug metabolism and clearance, Differences in the clinical and virologic manifestations of perinatal HIV infection secondary to the occurrence of primary infection in growing, immunologically immature persons, and Special considerations associated with adherence to antiretroviral treatment for infants, children and adolescents. This report addresses the pediatric-specific issues associated with antiretroviral treatment and provides guidelines to health care providers caring for infected infants, children, and adolescents. It is recognized that guidelines for antiretroviral use in pediatric patients are rapidly evolving. The Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children will review new data on an ongoing basis and provide regular updates to the guidelines
Survival, virological and immunological outcomes of HIV-infected children accessing ART at South African primary health care clinics
No full textIncludes bibliographical references.South Africa faces the world’s largest pediatric HIV epidemic. Combination antiretroviral therapy (ART) is the only effective treatment for HIV virus suppression. Pediatric HIV care has traditionally been provided in academic research and tertiary care facilities, however efforts to improve ART availability for children are ongoing through decentralization. Tygerberg Hospital physicians with training in pediatric HIV management are providing care in seven community-based primary health care (PHC) clinics in the greater Cape Town region. ART initiation and ongoing ART management for those down-referred from tertiary and district level facilities are provided. The HIV-related outcomes of this cohort have yet to be reported
Outcomes for efavirenz versus nevirapine-containing regimens for treatment of HIV-1 infection: a systematic review and meta-analysis.
Get PDFINTRODUCTION: There is conflicting evidence and practice regarding the use of the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) and nevirapine (NVP) in first-line antiretroviral therapy (ART). METHODS: We systematically reviewed virological outcomes in HIV-1 infected, treatment-naive patients on regimens containing EFV versus NVP from randomised trials and observational cohort studies. Data sources include PubMed, Embase, the Cochrane Central Register of Controlled Trials and conference proceedings of the International AIDS Society, Conference on Retroviruses and Opportunistic Infections, between 1996 to May 2013. Relative risks (RR) and 95% confidence intervals were synthesized using random-effects meta-analysis. Heterogeneity was assessed using the I(2) statistic, and subgroup analyses performed to assess the potential influence of study design, duration of follow up, location, and tuberculosis treatment. Sensitivity analyses explored the potential influence of different dosages of NVP and different viral load thresholds. RESULTS: Of 5011 citations retrieved, 38 reports of studies comprising 114 391 patients were included for review. EFV was significantly less likely than NVP to lead to virologic failure in both trials (RR 0.85 [0.73-0.99] I(2) = 0%) and observational studies (RR 0.65 [0.59-0.71] I(2) = 54%). EFV was more likely to achieve virologic success than NVP, though marginally significant, in both randomised controlled trials (RR 1.04 [1.00-1.08] I(2) = 0%) and observational studies (RR 1.06 [1.00-1.12] I(2) = 68%). CONCLUSION: EFV-based first line ART is significantly less likely to lead to virologic failure compared to NVP-based ART. This finding supports the use of EFV as the preferred NNRTI in first-line treatment regimen for HIV treatment, particularly in resource limited settings
Patterns and Predictors of CD4 T-Cell Counts Among Children Born to HIV-Infected Women in Tanzania.
Get PDFWe assessed age-specific CD4 T-cell counts and their determinants among Tanzanian children born to HIV-infected mothers to address a major research gap. A total of 474 HIV-uninfected and 69 HIV-infected children were followed until age of 12 months. Maternal predictors were measured during pregnancy and child predictors at birth and throughout the follow up. Child CD4 T-cell counts were evaluated at the age of 3 months and subsequent 3-month intervals; they decreased linearly among HIV-infected (beta = -8 cells per week; 95% CI -12 to -4; P = 0.0003) and increased linearly among HIV-uninfected children (beta = 4 cells/week; 95% CI 2-7; P = 0.0008). Decreased child counts were predicted by low child anthropometry, maternal HIV stage > or =2, and maternal mid-upper arm circumference <27 cm among HIV-infected children; and by weight-for-height <-2 z-score, maternal HIV stage > or =2, maternal erythrocyte sedimentation rate <81 mm/h and maternal haemoglobin <8.5 g/dl among HIV-uninfected children. The maternal and child predictors described may serve as intervention targets among HIV-exposed children
Burden of HIV infection and HIV-associated morbidity in Zimbabwean adolescents
Get PDFThis thesis concerns the clinical epidemiology of HIV infection in Zimbabwean adolescents. Without treatment, there is a very high risk of death in the early years of life in HIV-infected infants. However, in recent years increasing numbers of adolescents have been presenting to health care services with symptomatic HIV infection and with features suggesting longstanding disease. Population-based surveys in Southern Africa have shown HIV prevalence rates among older children and adolescents to be much higher than would be anticipated if HIV-infants were not surviving early childhood. The burden and spectrum of HIV-associated morbidity among adolescents was investigated with two studies at secondary and primary care level, respectively. The main finding was of an extremely high prevalence of HIV infection at both levels of the health system, with HIV infection being the single most common cause of hospital admission and death among adolescents. Mother-to-child transmission was the most likely source of HIV infection in the majority, suggesting a substantial epidemic of older survivors of vertical HIV infection. Other countries with severe HIV epidemics may be experiencing a similar trend as their HIV epidemics mature. The lack of awareness of the possibility of survival to older childhood and adolescence with maternally-acquired, untreated HIV infection results in many missed opportunities for diagnosis, with HIV infection frequently not diagnosed until presentation with a severe HIV-related illness. The median CD4 count in 3 HIV-infected adolescents in primary care was 350cells/µl compared to a median CD4 count of 151cells/µl among hospitalised adolescents, suggesting that HIV testing in primary care identifies HIV-infected adolescents at an earlier stage of infection. Provider-initiated HIV testing and counselling in primary care was highly acceptable to adolescents and guardians. Provision of care has been adversely affected by under-appreciation of the numbers of surviving adolescents living with HIV, and the special needs of this age-group have not been distinguished from those of younger children. Young people who have acquired HIV perinatally are stigmatised by society who assume they must have acquired it through "bad" behaviour themselves, since it is not widely appreciated that long-term survival following vertical infection is possible. Immediate priorities are earlier diagnosis of HIV infection and improved management of HIV-infected adolescents. Possible areas of intervention are discussed in the final chapter. Similar studies are needed in neighbouring countries to investigate the generalisability of these findings
Modelling the demographic impact of HIV/AIDS in South Africa and the likely impact of interventions
Get PDFThis paper describes an approach to incorporating the impact of HIV/AIDS and the effects of HIV/AIDS prevention and treatment programmes into a cohort component projection model of the South African population. The modelled HIV-positive population is divided into clinical and treatment stages, and it is demonstrated that the age profile and morbidity profile of the HIV-positive population is changing significantly over time. HIV/AIDS is projected to have a substantial demographic impact in South Africa. Prevention programmes - social marketing, voluntary counselling and testing, prevention of mother-to-child transmission and improved treatment for sexually transmitted diseases - are unlikely to reduce AIDS mortality significantly in the short term. However, more immediate reductions in mortality can be achieved when antiretroviral treatment is introduced.antiretroviral treatment, demographic impact, HIV/AIDS prevention, simulation model, South Africa
Access to art, adherence and drug resistance among HIV-Positive patients in rural Tanzania
Get PDFHIV is one of the worst pandemics in recent times, having affected more than 70 million and with a mortality rate close to 50%. Antiretroviral drugs fight viral replication and has improved life of HIV infected patients since it was introduced. Although ART has the potential of transforming the fatal disease into a chronic condition, there are critical issues surrounding access, adherence and resistance to the dug. We have systematically studied these questions and proposed a way forward to make ART more effective.
The first study explores the stock-out experience in two districts in rural Tanzania at the time when ART decentralization had just taken place. Out of stock was not a strange phenomenon with all sites have experienced stock-out of HIV test kits. The patients in the CTCs experienced HIV drugs and cotrimoxazole stock-out in the year preceding the study. Some of the strategies used appear to aggravate problems.
The adherence studies were showed parental caretaking a strong predictor of adherence in children and poverty and proximity playing acted as barrier to optimal adherence. ART adherence reporting overtime shows, patients tend to have better adherence during agricultural season. De-stigmatization campaigns and Direct Observed Therapy (DOT) interventions to children at risk of non-adherence are may improve adherence.
In our last study on predictors of ART resistance, children were more likely than adults to have resistances mutations. This might be linked with either the previous use of a single dose nevirapine and/or with non-adherence as observed in the adherence study. Improving adherence and low cost viral load monitoring may be appropriate solutions
