259 research outputs found
Progress in prevention of mother-to-child transmission of HIV infection in Ukraine: results from a birth cohort study
No full textBackground: Ukraine was the epicentre of the HIV epidemic in Eastern Europe, which has the most rapidly accelerating HIV epidemic world-wide today; national HIV prevalence is currently estimated at 1.6%. Our objective was to evaluate the uptake and effectiveness of interventions for prevention of mother-to-child transmission (PMTCT) over an eight year period within operational settings in Ukraine, within the context of an ongoing birth cohort study.Methods: The European Collaborative Study (ECS) is an ongoing birth cohort study in which HIV-infected pregnant women identified before or during pregnancy or at delivery were enrolled and their infants prospectively followed. Three centres in Ukraine started enrolling in 2000, with a further three joining in September 2006.Results: Of the 3356 women enrolled, 21% (689) reported current or past injecting drug use (IDU). Most women were diagnosed antenatally and of those, the proportion diagnosed in the first/second trimester increased from 47% in 2000/01 (83/178) to 73% (776/1060) in 2006/07 (p < 0.001); intrapartum diagnosis was associated with IDU (Adjusted odds ratio 4.38; 95% CI 3.19-6.02). The percentage of women not receiving any antiretroviral prophylaxis declined from 18% (36/205) in 2001 to 7% in 2007 (61/843) p < 0.001). Use of sdNVP alone substantially declined after 2003, with a concomitant increase in zidovudine prophylaxis. Median antenatal zidovudine prophylaxis duration increased from 24 to 72 days between 2000 and 2007. Elective caesarean section (CS) rates were relatively stable over time and 34% overall. Mother-to-child transmission (MTCT) rates decreased from 15.2% in 2001 (95% CI 10.2-21.4) to 7.0% in 2006 (95% CI 2.6-14.6). In adjusted analysis, MTCT risk was reduced by 43% with elective CS versus vaginal delivery and by 75% with zidovudine versus no prophylaxis.Conclusion: There have been substantial improvements in use of PMTCT interventions in Ukraine, including earlier diagnosis of HIV-infected pregnant women and increasing coverage with antiretroviral prophylaxis and the initial MTCT rate has more than halved. Future research should focus on hard-to-reach populations such as IDU and on missed opportunities for further reducing the MTCT rate
Pregnancy is associated with elevation of liver enzymes in HIV-positive women on antiretroviral therapy.
No full textThe objective of this study is to assess whether pregnancy is associated with an increased risk of liver enzyme elevation (LEE) and severe LEE in HIV-positive women on antiretroviral therapy (ART)
Durability of viral suppression with first-line antiretroviral therapy in patients with HIV in the UK: an observational cohort study.
No full textBACKGROUND: The length of time that people with HIV on antiretroviral therapy (ART) with viral load suppression will be able to continue before developing viral rebound is unknown. We aimed to investigate the rate of first viral rebound in people that have achieved initial suppression with ART, to determine factors associated with viral rebound, and to use these estimates to predict long-term durability of viral suppression. METHODS: The UK Collaborative HIV Cohort (UK CHIC) Study is an ongoing multicentre cohort study that brings together in a standardised format data on people with HIV attending clinics around the UK. We included participants who started ART with three or more drugs and who had achieved viral suppression (≤50 copies per mL) by 9 months after the start of ART (baseline). Viral rebound was defined as the first single viral load of more than 200 copies per mL or treatment interruption (for ≥1 month). We investigated factors associated with viral rebound with Poisson regression. These results were used to calculate the rate of viral rebound according to several key factors, including age, calendar year at start of ART, and time since baseline. RESULTS: Of the 16 101 people included, 4519 had a first viral rebound over 58 038 person-years (7·8 per 100 person-years, 95% CI 7·6-8·0). Of the 4519 viral rebounds, 3105 (69%) were defined by measurement of a single viral load of more than 200 copies per mL, and 1414 (31%) by a documented treatment interruption. The rate of first viral rebound declined substantially over time until 7 years from baseline. The other factors associated with viral rebound were current age at follow-up and calendar year at ART initiation (p<0·0001) and HIV risk group (p<0·0001); higher pre-ART CD4 count (p=0·0008) and pre-ART viral load (p=0·0003) were associated with viral rebound in the multivariate analysis only. For 1322 (29%) of the 3105 people with observed viral rebound, the next viral load value after rebound was 50 copies per mL or less with no regimen change. For HIV-positive men who have sex with men, our estimates suggest that the probability of first viral rebound reaches a plateau of 1·4% per year after 45 years of age, and 1·0% when accounting for the fact that 29% of viral rebounds are temporary elevations. INTERPRETATION: A substantial proportion of people on ART will not have viral rebound over their lifetime, which has implications for people with HIV and the planning of future drug development. FUNDING: UK Medical Research Council
Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy.
No full textThe objective of this study is to estimate life expectancies of HIV-positive patients conditional on response to antiretroviral therapy (ART)
Mortality and AIDS-defining events among young people following transition from paediatric to adult HIV care in the UK
No full textOBJECTIVES: To investigate risk of AIDS and mortality after transition from paediatric to adult care in a UK cohort of young people with perinatally acquired HIV. METHODS: Records of people aged ≥ 13 years on 31 December 2015 in the UK paediatric HIV cohort (Collaborative HIV Paediatric Study) were linked to those of adults in the UK Collaborative HIV Cohort (CHIC) cohort. We calculated time from transition to a new AIDS event/death, with follow-up censored at the last visit or 31 December 2015, whichever was the earliest. Cumulative incidence of and risk factors for AIDS/mortality were assessed using Kaplan-Meier and Cox regression. RESULTS: At the final paediatric visit, the 474 participants [51% female, 80% black, 60% born outside the UK, median (interquartile range) age at antiretroviral therapy (ART) initiation = 9 (5-13) years] had a median age of 18 (17-19) years and CD4 count of 471 (280-663) cell/μL; 89% were prescribed ART and 60% overall had a viral load ≤ 400 copies/mL. Over median follow-up in adult care of 3 (2-6) years, 35 (8%) experienced a new AIDS event (n = 25) or death (n = 14) (incidence = 1.8/100 person-years). In multivariable analyses, lower CD4 count at the last paediatric visit [adjusted hazard ratio = 0.8 (95% confidence interval: 0.7-1.0)/100 cells/μL increment] and AIDS diagnosis in paediatric care [2.7 (1.4-5.5)] were associated with a new AIDS event/mortality in adult care. CONCLUSIONS: Young people with perinatally acquired HIV transitioning to adult care with markers of disease progression in paediatric care experienced poorer outcomes in adult care. Increased investment in multidisciplinary specialized services is required to support this population at high risk of morbidity and mortality
Using age-specific mortality of HIV infected persons to predict anti-retroviral treatment need: a comparative analysis of data from five African population-based cohort studies.
No full textOBJECTIVES: To present a simple method for estimating population-level anti-retroviral therapy (ART) need that does not rely on knowledge of past HIV incidence. METHODS: A new approach to estimating ART need is developed based on calculating age-specific proportions of HIV-infected adults expected to die within a fixed number of years in the absence of treatment. Mortality data for HIV-infected adults in the pre-treatment era from five African HIV cohort studies were combined to construct a life table, starting at age 15, smoothed with a Weibull model. Assuming that ART should be made available to anyone expected to die within 3 years, conditional 3-year survival probabilities were computed to represent proportions needing ART. The build-up of ART need in a successful programme continuously recruiting infected adults into treatment as they age to within 3 years of expected death was represented by annually extending the conditional survival range. RESULTS: The Weibull model: survival probability in the infected state from age 15 = exp(-0.0073 × (age - 15)(1.69)) fitted the pooled age-specific mortality data very closely. Initial treatment need for infected persons increased rapidly with age, from 15% at age 20-24 to 32% at age 40-44 and 42% at age 60-64. Overall need in the treatment of naïve population was 24%, doubling within 5 years in a programme continually recruiting patients entering the high-risk period for dying. CONCLUSION: A reasonable projection of treatment need in an ART naive population can be made based on the age and gender profile of HIV-infected people
The effects of age on associations between markers of HIV progression and markers of metabolic function including albumin, haemoglobin and lipid concentrations.
No full textWe investigated whether age modified associations between markers of HIV progression, CD4 T lymphocyte count and HIV RNA viral load (VL), and the following markers of metabolic function: albumin, haemoglobin, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC)
Antiretroviral therapy and pregnancy outcome in HIV-infected women in the United Kingdom and Ireland
No full textThe aim of this thesis is to explore pregnancy and perinatal outcomes in diagnosed
HIV-infected women receiving antiretroviral therapy (ART) in the UK (United
Kingdom) and Ireland. Population-based surveillance data on HIV-infected pregnant
women and their children is collected through the National Study of HIV in
Pregnancy and Childhood (NSHPC), which includes information on over 8000
pregnancies delivered between 1990 and 2007. The majority of diagnosed infected
women now take highly active antiretroviral therapy (HAART) in pregnancy, which
reduces the risk of mother-to-child HIV transmission. However, there have been
concerns over the potential for maternal and fetal adverse effects, with conflicting
findings from European and American studies regarding the association between
HAART and premature delivery.
In this thesis, trends over time in the demographic characteristics of HIV-infected
pregnant women in the UK and Ireland are described, along with changes in the
uptake of interventions for preventing mother-to-child transmission. Transmission
rates are explored over a period when HAART was routinely available, and
subgroups of women managed in the context of regularly updated national guidelines
are compared with respect to their risk of transmission. Multivariable logistic
regression models are used to assess the association between type of ART exposure
in pregnancy and adverse outcomes including pre-eclampsia, prematurity, stillbirth,
neonatal death and congenital abnormality. In addition, using data from the European
Collaborative Study and the Pediatric Spectrum of HIV Disease project alongside the
UK and Ireland data, the effects of differences in populations and methodologies
(study design and analytical approach) on the observed association between HAART
and premature delivery are investigated, and a pooled analysis of individual motherchild
pairs is carried out. Finally, the risks and benefits of ART in terms of adverse
pregnancy outcomes and mother-to-child transmission were jointly modelled using
Monte Carlo simulation methods, to produce a risk-benefit ratio
The impact of a UK HIV-1 resistance database for the management and improvement of the clinical care of people living with HIV-1
No full textBackground: The introduction of highly active antiretroviral therapies (HAART) in 1996 to treat patients living with the human immunodeficiency virus type 1 (HIV-1), led to dramatic improvements in their mortality and morbidity. However, high levels of adherence to HAART regimens are required and due to the very nature of HIV-1: its high replicative capacity and lack of a proof reading mechanism, drug resistance mutations emerge, which impact on the ability of the drugs to suppress the patient’s circulating viruses. Genotypic resistance testing can determine whether mutations have developed which confer resistance to specific antiretrovirals (ARV) and thus enhance clinical care.
Methods: A clinical cohort database was developed to host the demographic, treatment and resistance mutation data for patients living with HIV-1 across the United Kingdom (UK) who had a genotypic resistance test (tests) conducted as part of their clinical care. These data were pooled and interrogated to determine the evolution and dynamics of resistance in targeted sub-groups of patients including treatment-naïve patients; treatment-experienced patients and their potential susceptibility to new ARV drugs; and the evolution of new subtype profiles within the clinical cohort and the impact of this on clinical outcomes. The over-riding aim of each of the studies was to improve the clinical care of patients with HIV-1 infection in the UK.
Results: In the treatment-naïve patient cohort (n=380), a resistance prevalence rate of 16.5% was determined. In the treatment-experienced cohort (n=1,786), the resistance prevalence rate was 68.1%. Of those treatment-experienced, 91.3% would be susceptible to the new ARV Etravirine (ETV) and 89.7% to Darunavir (DRV). In the subtype patient cohort (n=1,642), an increase in the prevalence of pure and recombinant non-B subtypes over time was demonstrated and characterised, as well as the identification of polymorphisms specific to non-B subtypes compared to subtype B.
Conclusions: The resistance prevalence rate of >10.0% in the treatment-naïve patient cohort supported the need to conduct genotypic resistance tests for all treatment-naïve patients with HIV-1 infection before commencement of HAART in order to ensure the patient was starting on the optimal first-line treatment regimen to control their virus. National and European guidelines were subsequently amended to reflect this requirement. The treatment-experienced patient cohort analyses confirmed the resistance mutations circulating within the treated HIV-1 community which are the source of transmitted resistance to the treatment-naïve patients. Further analyses of the treatment-experienced cohort suggested two new ARVs which were due to be licenced for use with HIV-1 patients would be “theoretically susceptible”, providing further treatment options for these patients with resistance mutations. The subtype patient cohort work determined that subtype characterisation should be introduced as part of clinical care due to the impact of non-B subtypes on the success of genotypic resistance testing, and the different mutational pathways which might occur, leading to resistance in different subtypes.
All these studies provided data and evidence of current issues which impacted on the clinical care of patients living with HIV-1 in the UK and influenced changes in guidelines on how best to manage and improve patient care
Treatment exhaustion of highly active antiretroviral therapy (HAART) among individuals infected with HIV in the United Kingdom: multicentre cohort study
No full textObjectives To investigate whether there is evidence that an increasing proportion of HIV infected patients is starting to experience increases in viral load and decreases in CD4 cell count that are consistent with exhaustion of available treatment options.Design Multicentre cohort study.Setting Six large HIV treatment centres in southeast England.Participants All individuals seen for care between. I January 1996 and 31 December 2002.Main outcome measures Exposure to individual antiretroviral drugs and drug classes, CD4 count, plasma HIV RNA burden.Results Information is available on 16 593 individuals (13 378 (80.6%) male patients, 10 340 (62.3%) infected via homosexual or bisexual sex, 4426 (26.7%) infected via heterosexual sex, median age 34 years). Overall, 10 207 of the 16 593 patients (61.5%) have been exposed to any antiretroviral therapy. This proportion increased from 41.2% of patients under follow up at the end of 1996 to 71.3% of those under follow up in 2002. The median CD4 count and HIV RNA burden of patients under follow up in each year changed from 270 cells/mm(3) and 4.34 log(10) copies/ml in 1996 to 408 cells/mm(3) and 1.89 log(10) copies/ml, respectively, in 2002. By 2002, 3060 (38%) of patients who had ever been treated with antiretroviral therapy had experienced all three main classes. Of these, around one quarter had evidence of "viral load failure" with all these three classes. Patients with three class failure were more likely to have an HIV RNA burden > 2.7 log(10) copies/ml and a CD4 count < 200 cells/mm(3).Conclusions The proportion of individuals with HfV infection in the United Kingdom who have been treated has increased gradually over time. A substantial proportion of these patients seem to be in danger of exhausting their options for antiretroviral treatment. New drugs with low toxicity, which are not associated with cross resistance to existing drugs, are urgently needed for such patients
- …
