How varying CD4 criteria for treatment initiation was associated with mortality of HIV-patients? A retrospective analysis of electronic health records from Andhra Pradesh, India.
ABSTRACT: Background:HIV treatment and care services were scaled up in 2007 in India with objective to increase HIV-care coverage. CD4 count based criteria was mainly used for treatment initiation with increasing threshold in later years. Therefore, this paper aimed to evaluate the survival by varying CD4 criteria for antiretroviral treatment (ART) initiation among of HIV-positive patients, and independent factors associated with the mortality. Methods:This retrospective cohort study included 127?949 HIV-positive patients aged ?15 years, who initiated ART between 2007 and 2013 in Andhra Pradesh state, India. The patient's demographic and clinical characteristics were extracted from the patient's health records from electronic Computerized Management Information System Software (CMIS). Incidence of mortality/100 person-years was calculated for CD4 and treatment initiation categories. Kaplan-Meier and multivariable Cox-regression analyses were used to explore the association. Results:Median CD4 count was 172 (inter-quartile range (IQR)?=?102-240) at the time of treatment initiation, and 19.3% of them had ??100 CD4 count. Incidence of mortality for the period 2007-08 (CD4???200 cells/mm3) was 8.5/100 person-years compared to 6.4/100 person-years at risk for the period 2012 onwards (CD4???350 cells/mm3). Earlier thresholds for treatment initiation showed higher risk of mortality (2007-08 (CD4???200 cells/mm3), adjusted hazard ratio (HR): 1.86, 95% confidence interval (CI): 1.68-2.07; 2009-11 (CD4???250 cells/mm3), HR?=?1.67, 95% CI?=?1.51-1.85) compared to 2012 onwards (CD4???350 cells/mm3) criteria for treatment initiation. Conclusions:Increasing CD4 threshold for treatment initiation over time was independently associated with lower risk of mortality. More efforts are required to detect and treat early, monitoring of follow-ups, promote health education to improve ART adherence, and provide supportive environment that encourages HIV-infected patients to disclose their HIV status in confidence.
Project description:Current WHO guidelines recommend initiating ART regardless of CD4+ cell count. In response, we conducted an observational cohort study to assess the effects of pre-ART CD4+ cell count levels on death, attrition, and death or attrition in HIV treated patients. This large HIV treatment cohort study (n?=?49,155) from 2010 to 2015 was conducted in Guangxi, China. We used a Cox regression model to analyze associations between pre-ART CD4+ cell counts and death, attrition, and death or attrition. The average mortality and ART attrition rates among all treated patients were 2.63 deaths and 5.32 attritions per 100 person-years, respectively. Compared to HIV patients with <350 CD4+ cells/mm3 at ART initiation, HIV patients with >500 CD4+ cells/mm3 at ART initiation had a significantly lower mortality rate (Adjusted hazard ratio: 0.56, 95% CI: 0.40-0.79), but significantly higher ART attrition rate (AHR: 1.17, 95% CI: 1.03-1.33). Results from this study suggest that HIV patients with high CD4+ cell counts at the time of ART initiation may be at greater risk of treatment attrition. To further reduce ART attrition, it is imperative that patient education and healthcare provider training on ART adherence be enhanced and account for CD4 levels at ART initiation.
Project description:In Cape Town, the roll-out of antiretroviral therapy (ART) has increased over the last decade with an estimated coverage of 63% of HIV- positive patients in 2013. The influence of ART on the characteristics of the population of HIV-positive patients presenting to the primary care TB programme is unknown. In this study, we examined trends in CD4 count distribution, ART usage and treatment outcomes among HIV-positive TB patients in Cape Town from 2009 to 2013.Data from the electronic TB register on all newly registered drug-sensitive TB patients ?18 years were analyzed retrospectively. Descriptive statistics were used to compare baseline characteristics, the CD4 count distribution and TB treatment outcomes both by year of treatment and ART status at the start of TB treatment. Survival analyses were used to assess the change in mortality risk during TB treatment over time, stratified by ART status at start of TB treatment.118,989 patients were treated over 5 years. HIV prevalence among TB patients decreased from 50.9% in 2009 to 49.0% in 2013. The absolute number of HIV-positive TB cases declined by 13.2% between 2010 and 2013. More patients entered the TB programme on ART in 2013 compared to 2009 (30.0% vs 9.9%). Among these, the CD4 count distribution showed a year by year shift to higher CD4 counts. In 2013, over 75% of ART-naïve TB patients still had a CD4 count <?350 cells/mm3. ART initiation among ART-naive patients increased from 37.0 to 77.7% and TB case fatality declined from 7.4 to 5.2% (p?<?0.001). In multivariate analysis a decrease in TB mortality was most strongly associated with CD4 count (Adjusted HR 0.82 per increase of 50 cells/mm3, 95% CI: 0.81-0.83, p?<?001) and the initiation of ART during TB treatment (Adjusted HR 0.39, 95% CI: 0.35-0.42, p?<?0.001).Comprehensive changes in the ART and TB treatment programmes resulted in incremental increases in ART coverage for HIV-positive TB patients and a subsequent decrease in TB case fatality due to increased ART uptake in HIV-positive ART-naïve patients. However TB still remained a major presenting opportunistic infection with the majority of cases occurring at low CD4 counts.
Project description:Prompt initiation of combination antiretroviral therapy (ART) is important to reduce comorbidity and mortality among people living with HIV, especially for those with a low CD4 cell count. However there is evidence that not everyone receives prompt initiation of ART after enrolling into HIV care. The current study investigated factors associated with failure to initiate ART within two years of entering into care among those with a CD4 count at or below 350 cells/mm3. The sample included 4,907 ART-naive patients with a CD4 count at or below 350 cells/mm3 enrolled between January 1, 2003 and December 31, 2012 at any of eight clinical sites in the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). The two-year risk of delayed ART initiation was estimated using a log-binomial regression model with stabilized inverse probability of censoring weights for those lost to follow-up. Adjusting for other factors, an earlier enrollment date was the sole demographic characteristic associated with an increased risk of delayed ART initiation. Higher CD4 count, lower viral load, and a prevalent AIDS diagnosis were clinical characteristics associated with delayed ART initiation. Gender, age, race/ethnicity and HIV risk factors such as reported male-to-male sexual contact and injection drug use were not associated with delayed ART initiation. This study identified characteristics of patients for whom treatment was strongly to moderately recommended but who did not initiate ART within two years of entering care. Despite the known benefits of early antiretroviral therapy initiation, a lower viral load measurement may continue to be an important clinical characteristic in the more recent era with current ART initiation guidelines. These findings provide a target for closer monitoring and intervention to reduce disparities in HIV care.
Project description:To estimate the impact of late ART initiation on HIV transmission among men who have sex with men (MSM) in Mexico.An HIV transmission model was built to estimate the number of infections transmitted by HIV-infected men who have sex with men (MSM-HIV+) MSM-HIV+ in the short and long term. Sexual risk behavior data were estimated from a nationwide study of MSM. CD4+ counts at ART initiation from a representative national cohort were used to estimate time since infection. Number of MSM-HIV+ on treatment and suppressed were estimated from surveillance and government reports. Status quo scenario (SQ), and scenarios of early ART initiation and increased HIV testing were modeled.We estimated 14239 new HIV infections per year from MSM-HIV+ in Mexico. In SQ, MSM take an average 7.4 years since infection to initiate treatment with a median CD4+ count of 148 cells/mm3(25th-75th percentiles 52-266). In SQ, 68% of MSM-HIV+ are not aware of their HIV status and transmit 78% of new infections. Increasing the CD4+ count at ART initiation to 350 cells/mm3 shortened the time since infection to 2.8 years. Increasing HIV testing to cover 80% of undiagnosed MSM resulted in a reduction of 70% in new infections in 20 years. Initiating ART at 500 cells/mm3 and increasing HIV testing the reduction would be of 75% in 20 years.A substantial number of new HIV infections in Mexico are transmitted by undiagnosed and untreated MSM-HIV+. An aggressive increase in HIV testing coverage and initiating ART at a CD4 count of 500 cells/mm3 in this population would significantly benefit individuals and decrease the number of new HIV infections in Mexico.
Project description:<h4>Background</h4> The number of HIV infected children receiving antiviral treatment in Guangxi is increasing. Understanding factors and trends of mortality and attrition in HIV-infected children under antiretroviral therapy (ART) was an urgent need to improve treatment outcomes. This study aimed to estimate mortality and attrition rates and identify factors that were associated with mortality and attrition after ART initiation among children with HIV in Guangxi, China between 2004 and 2018. <h4>Methods</h4> Cohort study data were extracted from the National Free Antiretroviral Treatment Program (NFATP) database, which has standard guidelines for core treatment indicators and other data at all HIV/AIDS treatment facilities in Guangxi. A total of 901 HIV-infected children who have started ART were included in the study. The study collected the following data: age, gender, WHO clinic stages before ART, CD4 cell count before ART, Cotrimoxazole prophylaxis (CTX) use before ART, initial ART regimen, malnutrition before ART, abnormal liver function before ART, abnormal kidney function before ART, severe anemia before ART, and the time lag between an HIV diagnosis and ART initiation. <h4>Results</h4> HIV-infected children under ART had a mortality rate of 0.87 per 100 person-years [95% Confidence Interval (CI) 0.63–1.11], and an attrition rate of 3.02 per 100 person-years (95% CI 2.57–3.47). Mortality was lower among children with a CD4 count between 200 and 500 copies/ml [Adjusted Hazard Ratio (AHR) 0.22, 95% CI 0.09–0.55], and CD4 count ≥500 copies/ml (AHR 0.10, 95% CI 0.03–0.29); but higher among children with late ART initiation at 1–3 months (AHR 2.30, 95% CI 1.07–4.94), and at ≥3 months (AHR 2.22, 95% CI 1.04–4.74). Attrition was lower among children with a CD4 count ≥500 copies/ml (AHR 0.62, 95% CI 0.41–0.95), but higher among children with late ART initiation at 1–3 months (AHR 1.55, 95% CI 1.05–2.30). <h4>Conclusion</h4> Supportive programs are needed to educate children's families and parents on early ART, link HIV-infected children to care and retain them in care among other programs that treat and manage the medical conditions of HIV-infected children before ART initiation.
Project description:In attaining UNAIDS targets of 90-90-90 to achieve epidemic control, understanding who the current utilizers of HIV treatment services are will inform efforts aimed at reaching those not being reached. A retrospective chart review of CAPRISA AIDS Treatment Program (CAT) patients between 2004 and 2013 was undertaken. Of the 4043 HIV-infected patients initiated on ART, 2586 (64.0%) were women. At ART initiation, men, compared to women, had significantly lower median CD4+ cell counts (113 vs 131 cells/mm3, p <0.001), lower median body mass index (BMI) (21.0 vs 24.2 kg/m2, p<0.001), higher mean log viral load (5.0 vs 4.9 copies/ml, p<0.001) and were significantly older (median age: 35 vs. 32 years, p<0.001). Men had higher mortality rates compared to women, 6.7 per 100 person-years (p-y), (95% CI: 5.8-7.8) vs. 4.4 per 100 p-y, (95% CI: 3.8-5.0); mortality rate ratio: 1.54, (95% CI: 1.27-1.87), p <0.001. Age-standardised mortality rate was 7.9 per 100 p-y (95% CI: 4.1-11.7) for men and 5.7 per 100 p-y (95% CI: 2.7 to 8.6) for women (standardised mortality ratio: 1.38 (1.15 to 1.70)). Mean CD4+ cell count increases post-ART initiation were lower in men at all follow-up time points. Men presented later in the course of their HIV disease for ART initiation with more advanced disease and experienced a higher mortality rate compared to women.
Project description:BACKGROUND:People who are asymptomatic and feel healthy, including pregnant women, may be less motivated to initiate ART or achieve high adherence. We assessed whether ART initiation, and viral suppression 6, 12 and 24-months after ART initiation, were lower in HIV-infected members of serodiscordant couples who initiated during pregnancy or with higher CD4 counts. METHODS:We used data from the Partners Demonstration Project, an open-label study of the delivery of integrated PrEP and ART (at any CD4 count) for HIV prevention among high-risk HIV serodiscordant couples in Kenya and Uganda. Differences in viral suppression (HIV RNA <400 copies/ml) among people initiating ART at different CD4 count levels (?350, 351-500, and >500 cells/mm3) and during pregnancy were estimated using Poisson regression. RESULTS:Of 865 HIV-infected participants retained after becoming eligible for ART during study follow-up, 95% initiated ART. Viral suppression 24-months after ART initiation was high overall (97%), and comparable among those initiating ART at CD4 counts >500, 351-500 and ?350 cells/mm3 (96% vs 97% vs 97%; relative risk [RR] 0.98; 95% CI: 0.93-1.03 for CD4 >500 vs <350 and RR 0.99; 95% CI: (0.93-1.06) for CD4 351-500 vs ?350). Viral suppression was as likely among women initiating ART primarily to prevent perinatal transmission as ART initiation for other reasons (p=0.9 at 6 months and p=0.5 at 12 months). CONCLUSIONS:Nearly all HIV-infected partners initiating ART were virally suppressed by 24 months, irrespective of CD4 count or pregnancy status. These findings suggest that people initiating ART at high CD4 counts or due to pregnancy can adhere to ART as well as those starting treatment with symptomatic HIV disease or low CD4 counts.
Project description:Antiretroviral treatment (ART) for HIV-positive patients has expanded rapidly in Asia over the last 10 years. Our study aimed to describe the time trends and risk factors for overall survival in patients receiving first-line ART in Asia.We included HIV-positive adult patients who initiated ART between 2003-2013 (n=16,546), from seven sites across six Asia-Pacific countries. Patient follow-up was to May 2014. We compared survival for each country and overall by time period of ART initiation using Kaplan-Meier curves. Factors associated with mortality were assessed using Cox regression, stratified by site. We also summarized first-line ART regimens, CD4+ T-cell count at ART initiation, and CD4+ T-cell and HIV viral load testing frequencies.There were 880 deaths observed over 54,532 person-years of follow-up, a crude rate of 1.61 (95% CI 1.51, 1.72) per 100 person-years. Survival significantly improved in more recent years of ART initiation. The survival probability at 4 years follow-up for those initiating ART in 2003-2005 was 92.1%, 2006-2009 was 94.3% and 2010-2013 was 94.5% (P<0.001). Factors associated with higher mortality risk included initiating ART in earlier time periods, older age, male sex, injecting drug use as HIV exposure and lower pre-ART CD4+ T-cell count. Concurrent with improved survival was increased tenofovir use, ART initiation at higher CD4+ T-cell counts and greater monitoring of CD4+ T-cells and HIV viral load.Our results suggest that HIV-positive patients from Asia have improved survival in more recent years of ART initiation. This is likely a consequence of improvements in treatment, patient management and monitoring over time.
Project description:INTRODUCTION:Up to 30% of individuals treated with antiretroviral therapy (ART) during chronic HIV fail to recover CD4 counts to >500 cells/mm3 despite plasma viral suppression. We investigated the frequency and associations of suboptimal CD4 recovery after ART started during acute HIV infection (AHI). METHODS:Participants who started ART in Fiebig I to V AHI with ?48 weeks of continuous documented HIV-RNA < 50 copies/mL were stratified by CD4 count at latest study visit to suboptimal immune recovery (SIR; CD4 < 350 cells/mm3 ), intermediate immune recovery (IIR; 350 ? CD4 < 500) and complete immune recovery (CIR; CD4 ? 500). Clinical and laboratory parameters were assessed at pre-ART baseline and latest study visit. Additional inflammatory and neurobehavioral endpoints were examined at baseline and 96 weeks. RESULTS:Of 304 participants (96% male, median 26 years old) evaluated after median 144 (range 60 to 420) weeks of ART initiated at median 19 days (range 1 to 62) post-exposure, 3.6% (n = 11) had SIR and 14.5% (n = 44) had IIR. Pre-ART CD4 count in SIR compared to CIR participants was 265 versus 411 cells/mm3 (p = 0.002). Individuals with SIR or IIR had a slower CD4 rate of recovery compared to those with CIR. Timing of ART initiation by Fiebig stage did not affect CD4 count during treatment. Following ART, the CD8+ T cell count (p = 0.001) and CD4/CD8 ratio (p = 0.047) were lower in SIR compared to CIR participants. Compared to the CIR group at week 96, the combined SIR and IIR groups had higher sCD14 (p = 0.008) and lower IL-6 (p = 0.04) in plasma, without differences in neuropsychological or psychiatric indices. CONCLUSIONS:Despite immediate and sustained treatment in AHI, suboptimal CD4 recovery occurs uncommonly and is associated with low pre-ART CD4 count as well as persistent low CD8 count and CD4/CD8 ratio during treatment.
Project description:The risk of HIV-1 related mortality is strongly related to CD4 count. Guidance on optimal timing for initiation of antiretroviral therapy (ART) is still evolving, but the contribution of HIV-1 infection to excess mortality at CD4 cell counts above thresholds for HIV-1 treatment has not been fully described, especially in resource-poor settings. To compare mortality among HIV-1 infected and uninfected members of HIV-1 serodiscordant couples followed for up to 24 months, we conducted a secondary data analysis examining mortality among HIV-1 serodiscordant couples participating in a multicenter, randomized controlled trial at 14 sites in seven sub-Saharan African countries.Predictors of death were examined using Cox regression and excess mortality by CD4 count and plasma HIV-1 RNA was computed using Poisson regression for correlated data.Among 3295 HIV serodiscordant couples, we observed 109 deaths from any cause (74 deaths among HIV-1 infected and 25 among HIV-1 uninfected persons). Among HIV-1 infected persons, the risk of death increased with lower CD4 count and higher plasma viral levels. HIV-1 infected persons had excess mortality due to medical causes of 15.2 deaths/1000 person years at CD4 counts of 250 - 349 cells/?l and 8.9 deaths at CD4 counts of 350 - 499 cells/?l. Above a CD4 count of 500 cells/?l, mortality was comparable among HIV-1 infected and uninfected persons.Among African serodiscordant couples, there is a high rate of mortality attributable to HIV-1 infection at CD4 counts above the current threshold (200 - 350 cells/?l) for ART initiation in many African countries. These data indicate that earlier initiation of treatment is likely to provide clinical benefit if further expansion of ART access can be achieved.Clinicaltrials.gov (NCT00194519).