Higher Baseline CD4 Research Articles

The factors associated with natural disease progression from HIV to AIDS in the absence of ART, a propensity score matching analysis.

This study aimed at comparing the factors associated with the natural progression between typical progressors (TPs) and rapid progressors (RPs) in HIV-infected individuals. A retrospective study was conducted on 2095 eligible HIV-infected individuals from 1995 to 2016 in a high-risk area of Henan Province, China. Propensity score matching was used to balance covariates, and the conditional logistic regression analyses were performed to explore the factors of natural disease progression among HIV infectors. A total of 379 pairs of RPs and TPs were matched. The standardised difference values of all covariates were less than 10%. HIV-infected individuals transmitted through sexual transmission (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.36-0.85) were more likely to progress to AIDS compared with those infected through contaminated blood. Older age at diagnosis of HIV-infected individuals (OR 0.72, 95% CI 0.58-0.89) exhibited a faster progression to AIDS. HIV-infected individuals identified through a unique survey (OR 7.01, 95% CI 2.99-16.44) were less likely to progress to AIDS compared with those identified through medical institutions. HIV-infected individuals who had higher baseline CD4+T cell counts (OR 3.37, 95% CI 2.59-4.38) had a slower progression to AIDS. These findings provide evidence for natural disease progression from HIV to AIDS between TPs and RPs.

Factors associated with CD4+/CD8+ T lymphocyte ratio normalization in acquired immunodeficiency syndrome patients after antiretroviral therapy

Objective To investigate the factors associated with CD4+ /CD8+ T lymphocyte ratio normalization in acquired immunodeficiency syndrome (AIDS) patients after antiretroviral therapy (ART). Methods The data of 1 188 human immunodeficiency virus (HIV)/AIDS patients from the national ART reporting system in Yuxi City, Yunnan Province between January 1, 2006 and December 31, 2016 were retrospectively collected and analyzed. The rate of CD4+ /CD8+ T lymphocyte ratio normalization after ART was calculated by lifetable. Cox proportional hazard models were used to analyze the factors associated with CD4+ /CD8+ T lymphocyte normalization in AIDS patients after ART. The Wilcoxon rank sum test was used for comparison between groups. Results The follow-up time was 3.8 (1.0-10.8) years. CD4+ /CD8+ T lymphocyte ratio normalization was documented in 95 patients with the rate of 1.89 per 100 person-years (95% confidence interval(CI) 1.52-2.27) after ART. The average time from ART to CD4+ /CD8+ T lymphocyte ratio normalized was 9.4 years. The cumulative normalization rate was 0.02 for the first year, 0.06 for the third year, 0.11 for the fifth year, 0.19 for the seventh year and 0.37 for the ninth year. By Cox proportional hazard models, the probability of CD4+ /CD8+ T lymphocyte ratio normalization in patients infected HIV by heterosexual contacts was 3.709 (95%CI 1.781-7.726) times higher than those by intravenous injection. The probability of CD4+ /CD8+ T lymphocyte ratio normalization in patients with baseline CD4+ T lymphocytes of 350-499 and more than 500 cell/μL groups were 2.792 (95%CI 1.196-6.519) and 3.832 (95%CI 1.648-8.913) times higher than those with baseline CD4+ T lymphocytes less than 200 cell/μL, respectively. The probability of normalization after ART in patients with higher baseline CD4+ /CD8+ T lymphocyte ratio was higher than those with baseline CD4+ /CD8+ T lymphocyte ratio≤ 0.20 (hazard ratio>1, all P<0.01). Conclusion The CD4+ /CD8+ T lymphocyte ratio normalization in AIDS patients after ART is associated with baseline CD4+ T lymphocyte counts, baseline CD4+ /CD8+ T lymphocyte ratio and HIV transmission mode. Key words: Acquired immunodeficiency syndrome; CD4-positive T-lymphocytes; CD8-positive T-lymphocytes; Antiretroviral therapy; Influencing factors

A longitudinal study on latent TB infection screening and its association with TB incidence in HIV patients

Latent TB infection (LTBI) in HIV patients, its treatment, and immunological recovery following highly active antiretroviral therapy (HAART) could interact and impact TB disease progression. We aim to examine the factors associated with LTBI and TB disease development among HIV patients. Longitudinal clinical and laboratory data were accessed from the largest HIV specialist clinic in Hong Kong, where HAART and yearly LTBI screening are routinely provided for HIV patients. Between 2002 and mid-2017, among 2079 HIV patients with 14119 person-years (PY) of follow-up, 32% of LTBI screened patients (n = 1740) were tested positive. The overall TB incidence was 1.26/100 PY from HIV diagnosis to HAART initiation, falling to 0.37/100 PY. A lower risk of TB disease progression was associated with local residence, Chinese ethnicity, negative baseline LTBI result, being on HAART, LTBI treatment, higher baseline CD4 and CD4/CD8 ratio. A positive test at baseline, but not subsequent testing results, was significantly associated with TB disease development. Baseline LTBI screening is an important strategy for identifying HIV patients at risk of TB disease progression. Routine repeat LTBI screening on an annual basis might not give additional benefits to patients on HAART with good immunological responses. Such practice should require re-evaluation.

Recording of HIV viral loads and viral suppression in South African patients receiving antiretroviral treatment: a multicentre cohort study.

Viral suppression in patients on antiretroviral treatment (ART) is critical to reducing HIV transmission and HIV-related mortality. Although many studies have evaluated factors associated with viral suppression, few have assessed the extent to which missing viral load data may bias results. We included data on all patients starting ART from 2005 to 2019 in eight South African cohorts participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration. Multivariable logistic regression models were used to determine factors associated with having a viral load measurement within 2 months of a scheduled testing date and having a viral load <400 RNA copies/ml ('viral suppression'). In a sensitivity analysis, missing viral loads were imputed based on patients' clinical and demographic characteristics and outcomes. Viral load tests were scheduled in 603,549 and 77,423 intervals in adults and children, respectively, but test results were recorded in only 40.7% and 41.2%, respectively. The proportion of recorded results suppressed was 85.7% in adults and 72.4% in children. After imputation of missing viral load measurements, viral suppression reduced slightly in adults (85.3%) and increased in children (73.2%). Predictors of virological suppression in adults, which included female sex, older age, higher baseline CD4+ T-cell count and recent testing year, were similar in the main analysis and after imputing missing viral loads. Although viral load information was frequently missing in the South African setting, estimates of viral suppression and predictors of viral suppression did not change substantially after adjusting for missing data.

Predictors of serological cure after treatment in patients with early syphilis: A retrospective observational study in Thailand.

Some patients with early syphilis who receive appropriate treatment do not reach a serological cure and have a persistent titer which does not meet the criteria for treatment failure (serofast state). This retrospective study aimed to determine the prevalence of serological cure and the serofast state as well as the factors associated with serological cure after treatment of patients with early syphilis. A serological cure was defined as occurring when there was a ≥4-fold decrease in nontreponemal titer, whereas patients with a ≥4-fold increase were considered as having either a treatment failure or reinfection. Nontreponemal titers that neither increased nor decreased ≥4-fold after treatment were considered to be in a serofast state. Seroreversion was defined as occurring when there was a negative test within 12 months of treatment. There were 179 patients with a mean age of 31.9 years; 174 (97.2%) were men, and 125 (70%) were HIV patients. Of the total, 174 (98%; 95% confidence interval 94.82-99.42%) patients achieved a serological cure, whereas five were in a serofast state 12 months after treatment. Those five serofast patients were all HIV-positive men, of which 4 (80%) had secondary-stage syphilis, a CD4 count ≤200 cells/μl and a titer <1:8. In a bivariate analysis, a serological cure was associated with a baseline Venereal Disease Research Laboratory >1:16 titers (P = 0.018), and a CD4 cell count >200 cells/μl in 6 months preceding treatment (P = 0.016). The median time to a serological cure was 96 days. Only 22 (12.3%) of the patients achieved seroreversion at 12 months after treatment. A retrospective medical record review is likely to have a selection bias, and in our study, 196 (52%) patients were excluded due to missing information. Most patients with early syphilis who achieved a serological cure at 12 months after treatment had high baseline Venereal Disease Research Laboratory titers and CD4 cell counts. However, only 22 (12.3%) had a negative Venereal Disease Research Laboratory titer after 1 year of treatment.

Acute HIV Infection and CD4/CD8 Ratio Normalization After Antiretroviral Therapy Initiation.

We estimated the effect of initiating virologically suppressive antiretroviral therapy (ART) during acute HIV infection versus chronic HIV infection (AHI vs. CHI) on CD4/CD8 ratio normalization. A prospective clinical cohort study. We included patients initiating ART with AHI and CHI between 2000 and 2015 and compared time from ART initiation to the first normal CD4/CD8 ratio (defined as CD4/CD8 ≥1) using Kaplan-Meier curves and multivariable Cox proportional hazards models. Patient time was censored at virologic failure, lost to follow-up, or death. We also characterized CD4, CD8, and CD4/CD8 trajectories over the first 3 years of ART. The 1198 patients were 27% female and 60% African American, with a median age of 37 years (interquartile range 28-47) at ART initiation. The 83 AHI patients were more likely male, younger, and of white race, than CHI patients. After 2 years of suppressive ART, 70% of AHI patients achieved a normal CD4/CD8 ratio, compared to 6%-38% of CHI patients, with greater likelihood of normalization at higher baseline CD4 counts. Time to normalization was shortest among AHI patients, followed by CHI patients with higher baseline CD4. The adjusted hazard ratio for time to normalization for AHI patients compared to CHI patients with baseline CD4 >350 was 4.33 (95% CI: 3.16 to 5.93). Higher baseline CD4/CD8 ratio was also associated with time to normalization (adjusted hazard ratio 1.54; 1.46, 1.63, per 0.1 increase in ratio). Initiating ART during AHI at higher baseline CD4 cell counts and CD4/CD8 ratios was associated with shorter time to CD4/CD8 ratio normalization.

Different Degrees of Immune Recovery Using Antiretroviral Regimens with Vonavir or Zidovudine/Lamivudine/Efavirenz in HIVPositive Patients Receiving First Line Treatment in Iran.

The initial antiretroviral therapy (ART) regimens recommended by most national treatment guidelines in resource-limited settings consist of two Nucleoside Reverse-Transcriptase Inhibitors (NRTIs) and one Non-Nucleoside Reverse- Transcriptase Inhibitor (NNRTI). The NRTIs are Zidovudine (AZT) or Stavudine (d4T) with Lamivudine (3TC); the NNRTI components are either Nevirapine (NVP) or Efavirenz (EFV). Existing data regarding the effectiveness of Vonavir compared to other first-line ART regimens in increasing CD4+ T cell counts are unsatisfactory. Immunological outcomes of 134 individuals who were on initial stage of antiretroviral therapy with Vonavir or a combination of Zidovudine/Lamivudine and Efavirenz were analyzed. The immunological response was then assessed during 28 weeks. Both groups demonstrated a significant increase in their CD4+ T cell count which was greater in Zidovudine/Lamivudine and Efavirenz treated group. We observed a noticeable increase in CD4+ T cells rates in the first three months of therapy; however, our results indicated a greater increase of cell counts in individuals with baseline CD4 lower than 100 cells/mm3 treated with Vonavir in first 12 weeks of treatment compared to those with higher baseline CD4. A rapid CD4+ Tcell increase occurred shortly after beginning ART consisting either Vonavir or combination of Zidovudine, Lamivudine and Efavirenz. Late increases in CD4+ T cell counts were more pronounced in therapy using Zidovudine/ Lamivudine and Efavirenz.

High Baseline CD4 Count and Exclusive Breastfeeding Are Associated with Lower Rates of Mother to Child HIV Transmission in Northwestern Uganda: A Two-Year Retrospective Cohort Study

Background. Under Option B plus, the transmission of Human Immunodeficiency Virus (HIV) along the Early Infant Diagnosis (EID) of HIV cascade remains unknown. We described HIV transmission along the EID cascade and determined associated factors at Arua Regional Referral Hospital, Northwestern Uganda. Methods. Data on 295 mother-baby pairs in EID care (January 2014 and April 2015) was extracted, cleaned, and analysed in STATA. Univariate, bivariate, and multivariate analyses were performed. Independently associated factors were stated in adjusted odds ratio (AOR), 95% confidence interval (CI), and p-values. Results. 233 (89.0%) mothers were above 30 years, 251 (85.1%) were in World Health Organization (WHO) clinical stages I/II at enrolment, 170 (57.6%) attended antenatal care (ANC) visits during recent pregnancy, and 204 (69.1%) delivered in a health facility. Meanwhile, 257 (87.1%) HIV Exposed Infants (HEIs) received Nevirapine prophylaxis from birth up to 6 weeks and 245 (83.0%) were exclusively breastfed during the first 6 months. Of 295 mother-baby pairs, 25 (8.5%) HEIs turned HIV-positive along the EID cascade. Baseline maternal CD4 count of more than 500 cells/ul compared to less than 500 cells/ul (adjusted odds ratio (AOR) = 0.29; 95% Confidence Interval (CI): 0.10–0.85; p = 0.024) and exclusive breastfeeding (EBF) in the first 6 months of delivery in contrast to not EBF in the first 6 months (AOR = 0.17; 95% CI: 0.52–0.55; p = 0.003) reduced HIV transmission. Meanwhile, ANC visits, place of delivery, time of Nevirapine initiation, and maternal antiretroviral therapy use were not significantly associated with infant HIV transmission. Conclusion. HIV transmission was high. High baseline CD4 count and exclusive breastfeeding reduced HIV transmission.

Long terms trends in CD4+ cell counts, CD8+ cell counts, and the CD4+ : CD8+ ratio.

Model trajectories of CD4+ and CD8+ cell counts after starting combination antiretroviral therapy (ART) and use the model to predict trends in these counts and the CD4+ : CD8+ ratio. Cohort study of antiretroviral-naïve HIV-positive adults who started ART after 1997 (ART Cohort Collaboration) with more than 6 months of follow-up data. We jointly estimated CD4+ and CD8+ cell count trends and their correlation using a bivariate random effects model, with linear splines describing their population trends, and predicted the CD4+ : CD8+ ratio trend from this model. We assessed whether CD4+ and CD8+ cell count trends and the CD4+ : CD8+ ratio trend varied according to CD4+ cell count at start of ART (baseline), and, whether these trends differed in patients with and without virological failure more than 6 months after starting ART. A total of 39 979 patients were included (median follow-up was 53 months). Among patients with baseline CD4+ cell count at least 50 cells/μl, predicted mean CD8+ cell counts continued to decrease between 3 and 15 years post-ART, partly driving increases in the predicted mean CD4+ : CD8+ ratio. During 15 years of follow-up, normalization of the predicted mean CD4+ : CD8+ ratio (to >1) was only observed among patients with baseline CD4+ cell count at least 200 cells/μl. A higher baseline CD4+ cell count predicted a shorter time to normalization. Declines in CD8+ cell count and increases in CD4+ : CD8+ ratio occurred up to 15 years after starting ART. The likelihood of normalization of the CD4+ : CD8+ ratio is strongly related to baseline CD4+ cell count.

Ultrasensitive Human Immunodeficiency Virus Type 1 Viral Load as a Marker of Treatment Choice for Simplification Strategies.

Using 3 randomized Protease inhibitor (PI) monotherapy studies: Kalesolo, Dream and Monoi, we performed a pooled-analysis. Our objective was to determine in PI monotherapy and standard tritherapy: 1) distribution of ultrasensitive viral load (USVL) at week 96 (W96); 2) factors associated with virological failure (VF) at W96 and 3) factors associated with USVL<1 copy at W96. VF was defined as 2 consecutive measurements of Human Immunodeficiency Virus Type 1 RNA viral load>50 copies/mL and analysed in Intention-To-Treat. A logistic model was used to investigate which variables were predictive of a VF and Fisher test to investigate differences in USVL at W96. Among 609 patients, 73% were male with median age of 44.4 years (IQR 39.8-52.1), baseline CD4/CD8 ratio was 0.8 (IQR 0.6-1.10), baseline CD4 was 564.5/mm3 (IQR 422-707) and 59% presented a baseline USVL<1 copy/mL. At W96, the proportion of USVL<1 copy/mL was significantly different between PI monotherapy and standard tritherapy in pooled-analysis (65% versus 74%; p=0.04). Overall, baseline USVL<1copy/mL, tritherapy and to be a female were associated with USVL<1 copy/mL at W96 (p<0.0001, p=0.049 and p=0.006). In PI monotherapy receiving DRV/r was associated with USVL<1 copy/mL at W96 (p=0.003). Factors associated to virological succes at W96 were higher baseline CD4 (p=0.034) and baseline USVL<1 copy/mL (p=0.0005). Pooled-analysis of 3 PI monotherapy trials showed better efficacy of tritherapy in terms of USVL at W96. Furthermore regarding USVL at W96, to receive LPV/r seems to be more deleterious than DRV/r. Baseline USVL impacts VF at W96 more specifically in tritherapy arm. NCT00421551, NCT00946595, and NCT00140751.

Loss to follow-up and associated factors of patients in the National AIDS Program in Thailand.

Loss to follow-up (LTFU) is a crucial indicator to evaluate the effectiveness of HIV care and treatment programmes. We assessed the LTFU rate and associated factors of Thai HIV-infected patients who enrolled in the National AIDS Program (NAP) for two periods: prior to (pre-ART) and after starting ART (ART-patients). Thai HIV patients aged ≥15 years enrolled in NAP from 2008 to 2014. Vital status was ascertained by linkage with the National Death Registry. Competing risk models were used to calculate the adjusted sub-distribution hazards (aSHR) for LTFU for pre-ART and ART-patients, with death considered as a competing risk. A total of 157,026 patients registered in care and were included in analyses. The cumulative incidence of LTFU in pre-ART patients at 1 year was 10.2%, whereas in ART-patients it was 12.8%. Among pre-ART patients, younger age (<30 versus ≥45 years, aSHR 1.60, 95% CI 1.49, 1.72), less advanced HIV stage (aSHR 1.29, 95% CI 1.21, 1.37) and higher CD4+ T-cell count (≥350 versus <100, aSHR 6.31, 95% CI 5.74, 6.95) had a higher chance of LTFU. ART-patients with high baseline CD4+ T-cell count (CD4 ≥350 versus CD4 <50, aSHR 2.06, 95% CI 1.97, 2.15) and non-advanced HIV stage had increased risk of LTFU. Our findings provide new evidence of the LTFU rate in Thai HIV-infected patients in NAP. Emphasis needs to be placed on improving follow-up in all patients with higher CD4+ T-cell counts. LTFU will be important to monitor as programmes move to commence ART regardless of CD4+ T-cell count.

Incidence and Risk Factors for Incident Syphilis among HIV-1-Infected Men Who Have Sex with Men in a Large Urban HIV Clinic in Tokyo, 2008-2015.

BackgroundThe epidemiology of incident syphilis infection among HIV-1-infected men who have sex with men (MSM) largely remains unknown.MethodsThe incidence and risk factors for incident syphilis (positive TPHA and RPR> = 1:8) among HIV-1-infected MSM who visited a large HIV clinic in Tokyo for the first time between 2008 and 2013 were determined, using clinical data and stored blood samples taken every three months for screening and determination of the date of incident syphilis. Poisson regression compared the incidence of syphilis at different observation periods.ResultsOf 885 HIV-1-infected MSM with baseline data, 34% either presented with active syphilis at baseline (21%) or became infected with syphilis during follow-up (13%). After excluding 214 patients (MSM with syphilis at baseline (n = 190) and no follow-up syphilis test (n = 24)), of 671 men, 112 (17%) developed incident syphilis with an incidence of 43.7/1,000 person-years [95% CI, 36.5–52.3]. The incidence decreased slightly during observation period although the trend was not significant (2008–2009: 48.2/1,000 person-years, 2010–2011: 51.1/1,000 person-years, 2012–2013: 42.6/1,000 person-years, 2014 to 2015: 37.9/1,000 person-years, p = 0.315). Multivariable analysis identified young age (<33 years versus >40, HR 4.0, 95%CI 2.22–7.18, p<0.001), history of syphilis at baseline (HR 3.0, 95%CI 2.03–4.47, p<0.001), positive anti-amoeba antibody (HR 1.8, 95%CI 1.17–2.68, p = 0.006), and high baseline CD4 count (CD4 ≥350 /μL versus CD4 <200, HR 1.6, 95%CI 1.00–2.53, p = 0.050) as risk factors for incident syphilis. Incidence of syphilis was particularly high among young patients (age <33 years: 60.1/1,000 person-years). Interestingly, 37% of patients with incident syphilis were asymptomatic.ConclusionsAlthough incidence of syphilis did not increase during the observation period, it was high among HIV-1-infected MSM, especially among young HIV-1-infected MSM and those with history of syphilis, in Tokyo. Regular screening for syphilis needs to be strictly applied to this population.

Long-Term Outcomes on Antiretroviral Therapy in a Large Scale-Up Program in Nigeria.

BackgroundWhile there has been a rapid global scale-up of antiretroviral therapy programs over the past decade, there are limited data on long-term outcomes from large cohorts in resource-constrained settings. Our objective in this evaluation was to measure multiple outcomes during first-line antiretroviral therapy in a large treatment program in Nigeria.MethodsWe conducted a retrospective multi-site program evaluation of adult patients (age ≥15 years) initiating antiretroviral therapy between June 2004 and February 2012 in Nigeria. The baseline characteristics of patients were described and longitudinal analyses using primary endpoints of immunologic recovery, virologic rebound, treatment failure and long-term adherence patterns were conducted.ResultsOf 70,002 patients, 65.2% were female and median age was 35 (IQR: 29–41) years; 54.7% were started on a zidovudine-containing and 40% on a tenofovir-containing first-line regimen. Median CD4+ cell counts for the cohort started at 149 cells/mm3 (IQR: 78–220) and increased over duration of ART. Of the 70,002 patients, 1.8% were reported as having died, 30.1% were lost to follow-up, and 0.1% withdrew from treatment. Overall, of those patients retained and with viral load data, 85.4% achieved viral suppression, with 69.3% achieving suppression by month 6. Of 30,792 patients evaluated for virologic failure, 24.4% met criteria for failure and of 45,130 evaluated for immunologic failure, 34.0% met criteria for immunologic failure, with immunologic criteria poorly predicting virologic failure. In adjusted analyses, older age, ART regimen, lower CD4+ cell count, higher viral load, and inadequate adherence were all predictors of virologic failure. Predictors of immunologic failure differed slightly, with age no longer predictive, but female sex as protective; additionally, higher baseline CD4+ cell count was also predictive of failure. Evaluation of long-term adherence patterns revealed that the majority of patients retained through 84 months maintained ≥95% adherence.ConclusionWhile improved access to HIV care and treatment remains a challenge in Nigeria, our study shows that a high quality of care was achieved as evidenced by strong long-term clinical, immunologic and virologic outcomes.

PP.21.06] EARLY IMMUNE ACTIVATION PROFILE IN STAGE I HYPERTENSION AND ITS PREDICTIVE RISK VALUE IN 5 YEAR FOLLOW UP

Objective: To describe immune basal profile and its predictive value on the incidence of cardiovascular events and blood pressure evolution in hypertensive stage I subjects. Design and method: Patients with mild hypertension were recruited with at least 5 years from diagnosis. Exclusion criteria were: GFR> 60 ml/min/1.73 m2 (MDRD) microalbuminuria> 30 mg/24 hs, previous CV events, autoimmune disease, use of imunomodulatory agents or corticosteroids. At entry and follow up office and 24 hs ambulatory BP was measured; cell subpopulations were measured by flow cytometry in peripheral blood and direct cell count respectively, using T and dendritic cells monoclonal antibodies. End points were defined as the incidence of stroke, ischemic heart disease, new onset diabetes, cardiovascular and all-cause mortality, and number/doses of antihypertensive drugs and BP. Results: 72 subjects were classified in two groups: a) hipertensives, n:50 (24 women, 55.0 ± 9.0 years, 132 ± 6.4/80.3 ± 8.7 mmHg, number of antihypertensive drugs 2.0 ± 1.5.) and b) normotensive, n:22 (12 women, 53 ± 11 years). Median follow up: 5.4. ± 3.3 years. The distribution of immune markers in hypertensive was expressed as median x 106 cells / L (range): 650.40 CD4 + (272–980), CD8 + 110.37 (80–143), CD4 + / CD8 + 5.30 (2.50–9.90), CD25 + 86.90 (80.0–99.6), CD86 + (69.8–448.70), CD83 + (69.40–145). Compared to controls, HTs had a profile with higher CD3 + CD4 + CD83 + CD86 + (<0.001). At follow up, we found a direct association between the RR of events in the entire population (HT and NT) with higher baseline CD4 +, CD83 +, CD86 +, increased CD4 + / CD8 +, CD25 + lower ratio / CD4 + (<0.001). HTs had more events than NTs: 9.4 vs 0% stroke, ischemic heart disease 12.5 vs 7.1%, all-cause mortality 2 vs 0%. Among hypertensive greater CD4 + / CD8 + and / or lower ratio CD25 + / CD4 + were highly predictive of new cases of DBT. Conclusions: In hypertensive stage I we identified a specific immune cell activation pattern.

Life expectancy after initiation of combination antiretroviral therapy in Thailand.

Access to combination antiretroviral therapy (cART) has decreased mortality in HIV-positive people. We aimed to estimate the expected additional years of life in HIV-positive Thai people after starting cART through the National AIDS Program (NAP), administered by the Thai National Health Security Office (NHSO). The NHSO database collects characteristics of all Thai HIV-infected patients through the National AIDS Program, including linkage with the National Death Registry for vital status. This study included patients aged ≥15 years at cART initiation between 2008 and 2014. The abridged life table method was used to construct life tables stratified by sex and baseline CD4+ T-cell count. Life expectancy was defined as the additional years of life from age at starting cART. 201,688 eligible patients were included in analyses, contributing 618,837 person-years of follow-up. Median CD4+ T-cell count was 109 cells/mm3 and median age 37 years. The overall life expectancy after cART initiation at age 20 was 25.4 (95% CI, 25.3, 25.6) years and 20.6 (95% CI, 20.5, 20.7) at age 35 years. Life expectancy at baseline CD4+ T-cell count ≥350 cells/mm3 was 51.9 (95% CI, 51.0, 52.9) years for age 20 years and 43.2 (95% CI, 42.4, 44.1) years for age 35 years, close to life expectancy in the general Thai population. Increasing life expectancy with higher baseline CD4+ T-cell counts supports the guideline recommendations to start cART irrespective of CD4+ T-cell count. These results are beneficial to forecast the treatment cost and develop health policies for people living with HIV in Thailand and Asia.

CD4 Count Recovery After Initiation of Antiretroviral Therapy in Patients Infected With Human Immunodeficiency Virus

BackgroundPrognosis for patients infected with human immunodeficiency virus (HIV) correlates with levels of CD4+ T cells. Initiation of antiretroviral therapy (ART) interrupts multiple points in the virus life cycle, causing an increase in CD4 cells. The rate at which the CD4 count recovers is highly variable and subject to influence by many factors. MethodsWe performed a deidentified data review to determine factors influencing the rate of CD4 count recovery after ART initiation. The associations between the changes in CD4 count from baseline at 5 time points, and factors including age, race, weight, baseline CD4 count, baseline viral load, specific ART medications and various comorbidities, were evaluated with univariate and multivariate analyses, using t-test, analysis of variance and multiple regressions. ResultsCD4 count continued to rise even up to 10 years after ART initiation, with the steepest increase in the first 3 months. High baseline viral load and low baseline CD4 count had the most consistent positive influence on CD4 count recovery rate across the 5 measured time points. Other factors that were significantly positively associated with CD4 recovery rate included younger baseline age, higher baseline weight and female gender. ConclusionsCD4 counts in HIV positive patients who consistently take ART continue to increase out to at least 10 years. Patients with a more advanced HIV infection at baseline, as indicated by high viral loads or low CD4 counts, have a greater rate of CD4 count recovery after starting ART, possibly because their CD4 counts have more room for improvement.

Identification of a novel and severe pattern of efavirenz drug-induced liver injury in South Africa.

Efavirenz now forms part of many antiretroviral regimens in low and middle-income countries. Efavirenz-related drug-induced liver injury is not well characterized but is thought to occur less frequently than with nevirapine. We describe our observation of three defined clinicopathological patterns of injury, one of which, submassive necrosis, is associated with significant morbidity and mortality. A high baseline CD4, younger age and possibly female gender, predicts for the injury.

Mortality According to CD4 Count at Start of Combination Antiretroviral Therapy Among HIV-infected Patients Followed for up to 15 Years After Start of Treatment: Collaborative Cohort Study.

CD4 count at start of combination antiretroviral therapy (ART) is strongly associated with short-term survival, but its association with longer-term survival is less well characterized. We estimated mortality rates (MRs) by time since start of ART (<0.5, 0.5-0.9, 1-2.9, 3-4.9, 5-9.9, and ≥10 years) among patients from 18 European and North American cohorts who started ART during 1996-2001. Piecewise exponential models stratified by cohort were used to estimate crude and adjusted (for sex, age, transmission risk, period of starting ART [1996-1997, 1998-1999, 2000-2001], and AIDS and human immunodeficiency virus type 1 RNA at baseline) mortality rate ratios (MRRs) by CD4 count at start of ART (0-49, 50-99, 100-199, 200-349, 350-499, ≥500 cells/µL) overall and separately according to time since start of ART. A total of 6344 of 37 496 patients died during 359 219 years of follow-up. The MR per 1000 person-years was 32.8 (95% confidence interval [CI], 30.2-35.5) during the first 6 months, declining to 16.0 (95% CI, 15.4-16.8) during 5-9.9 years and 14.2 (95% CI, 13.3-15.1) after 10 years' duration of ART. During the first year of ART, there was a strong inverse association of CD4 count at start of ART with mortality. This diminished over the next 4 years. The adjusted MRR per CD4 group was 0.97 (95% CI, .94-1.00; P = .054) and 1.02 (95% CI, .98-1.07; P = .32) among patients followed for 5-9.9 and ≥10 years, respectively. After surviving 5 years of ART, the mortality of patients who started ART with low baseline CD4 count converged with mortality of patients with intermediate and high baseline CD4 counts.

The impact of transient combination antiretroviral treatment in early HIV infection on viral suppression and immunologic response in later treatment.

Objective:Effects of transient combination antiretroviral treatment (cART) initiated during early HIV infection (EHI) remain unclear. We investigate whether this intervention affects viral suppression and CD4+ cell count increase following its reinitiation in chronic infection (CHI).Design:Longitudinal observational study.Methods:We identified adult patients from Concerted Action of Seroconversion to AIDS and Death in Europe who seroconverted after 1/1/2000, had a 12 months or less HIV test interval and initiated cART from naive. We classified individuals as ‘pretreated in EHI’ if treated within 6 months of seroconversion, interrupted for at least 12 weeks, and reinitiated during CHI. Statistical analysis was performed using survival analysis methods and mixed models.Results:Pretreated and initiated in CHI groups comprised 202 and 4263 individuals, with median follow-up after CHI treatment 4.5 and 3 years, respectively. Both groups had similar virologic response and relapse rates (P = 0.585 and P = 0.206) but pretreated individuals restarted treatment with higher baseline CD4+ cell count (∼80 cells/μl; P < 0.001) and retained significantly higher CD4+ cell count for more than 3 years after treatment (re)initiation. Assuming common baseline CD4+ cell count, differences in CD4+ cell count slopes were nonsignificant. Immunovirologic response to CHI treatment was not associated with timing or duration of the transient treatment.Conclusion:Although treatment interruptions are not recommended, stopping cART initiated in EHI does not seem to reduce the chance of a successful outcome of treatment in CHI.

Role of CD5-negative CD8&lt;sup&gt;+&lt;/sup&gt; T Cells in Adaptation to Antigenic Variation of Human Immunodeficiency Virus Type 1

Purpose: To investigate the effect of 3-oxotirucalla-7, 24-dien-21-oic acid on CD8 + T cell recovery in human immunodeficiency virus type 1 (HIV-1) disease. Methods: The increase in the rates of CD8 + T cells over 48 weeks following treatment with 3- oxotirucalla-7, 24-dien-21-oic acid was investigated. Plasma HIV-1 load was measured by Versant™ HIV-1 RNA 3.0 branched chain DNA assay while flow cytometry was used for blood CD4 cell counts. For the analysis of the data obtained, Stata version 9.0 was employed. Results: 3-Oxotirucalla-7, 24-dien-21-oic acid treatment increased CD8 + T cell count from a median of 89 % at baseline to 99 % at 48 weeks. The proportion of patients with CD8 + T cell count 500 cells/μL at 48 weeks, 23 % had baseline CD8 + T cell counts of < 50 cells/μL. However, the proportion of the patients that attained CD8 + T count of 200 cells/μL at 48 weeks was lower than those with higher baseline CD4 cell counts. Conclusion: 3-Oxotirucalla-7,24-dien-21-oic acid treatment induces greater tendency for CD8 + T cell recovery in patients with baseline CD8 + T cell counts < 50 cells/μL during 48 weeks of treatment. Therefore, 3-oxotirucalla-7,24-dien-21-oic acid is a promising agent for CD8 + T cell count recovery in patients with HIV infection. Keywords: CD8 + T cells, HIV infection, Oleanolic acid, Lymphocyte cell, Cell recovery