scholarly journals Markov modelling of viral load adjusting for CD4 orthogonal variable and multivariate conditional autoregressive mapping of the HIV immunological outcomes among ART patients in Zimbabwe

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Zvifadzo Matsena Zingoni ◽  
Tobias F. Chirwa ◽  
Jim Todd ◽  
Eustasius Musenge
Keyword(s):  
Disease Progression ◽  
Viral Suppression ◽  
Transition Rates ◽  
Hiv Disease ◽  
Art Initiation ◽  
Relative Risks ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Conditional Autoregressive ◽  
Cd4 Cell

Abstract Background This study aimed to jointly model HIV disease progression patterns based on viral load (VL) among adult ART patients adjusting for the time-varying “incremental transients states” variable, and the CD4 cell counts orthogonal variable in a single 5-stage time-homogenous multistate Markov model. We further jointly mapped the relative risks of HIV disease progression outcomes (detectable VL (VL ≥ 50copies/uL) and immune deterioration (CD4 < 350cells/uL) at the last observed visit) conditional not to have died or become loss to follow-up (LTFU). Methods Secondary data analysis of individual-level patients on ART was performed. Adjusted transition intensities, hazard ratios (HR) and regression coefficients were estimated from the joint multistate model of VL and CD4 cell counts. The mortality and LTFU transition rates defined the extent of patients’ retention in care. Joint mapping of HIV disease progression outcomes after ART initiation was done using the Bayesian intrinsic Multivariate Conditional Autoregressive prior model. Results The viral rebound from the undetectable state was 1.78times more likely compared to viral suppression among patients with VL ranging from 50-1000copies/uL. Patients with CD4 cell counts lower than expected had a higher risk of viral increase above 1000copies/uL and death if their VL was above 1000copies/uL (state 2 to 3 (λ23): HR = 1.83 and (λ34): HR = 1.42 respectively). Regarding the time-varying effects of CD4 cell counts on the VL transition rates, as the VL increased, (λ12 and λ23) the transition rates increased with a decrease in the CD4 cell counts over time. Regardless of the individual’s VL, the transition rates to become LTFU decreased with a decrease in CD4 cell counts. We observed a strong shared geographical pattern of 66% spatial correlation between the relative risks of detectable VL and immune deterioration after ART initiation, mainly in Matabeleland North. Conclusion With high rates of viral rebound, interventions which encourage ART adherence and continual educational support on the barriers to ART uptake are crucial to achieve and sustain viral suppression to undetectable levels. Area-specific interventions which focus on early ART screening through self-testing, behavioural change campaigns and social support strategies should be strengthened in heavily burdened regions to sustain the undetectable VL. Sustaining undetectable VL lowers HIV transmission in the general population and this is a step towards achieving zero HIV incidences by 2030.

Immunologic Benefits of Enfuvirtide in Patients Enrolled in a Drug Assistance Program

2008 ◽  
Vol 42 (5) ◽  
pp. 621-626 ◽  
Author(s):  
Parya Saberi ◽  
Nikolai H Caswell ◽  
Cristina I Gruta ◽  
Jason N Tokumoto ◽  
Betty J Dong
Keyword(s):  
Cell Count ◽  
Viral Suppression ◽  
Cd4 Cell Count ◽  
Hiv Rna ◽  
Cell Counts ◽  
Background Regimen ◽  
Cd4 Cell Counts ◽  
Cd4 Cell ◽  
Cell Count Increase

Background: Randomized clinical trials have demonstrated that enfuvirtide plus an optimized background regimen can cause a significant increase in CD4+ cell counts and a reduction in HIV RNA levels. Objective: To describe and anaiyze CD4+ cell count and HIV RNA changes in HIV-infected patients receiving enfuvirtide and a prescribed background regimen (PBR) in a primarily clinical setting. Methods: A retrospective review from September 1998 through August 2005 of CD4+ cell counts and HIV RNA changes from baseline was conducted in patients receiving enfuvirtide. Data were stratified and analyzed according to baseline CD4+ cell count and HIV RNA. Results: A mean CD4+ cell count increase of approximately 102 cells/mm3 was observed, regardless of baseline CD4+ cell count, in 187 patients receiving enfuvirtide during a mean of 19.4 months of follow-up. During 3 years of follow-up, patients initiating enfuvirtide at CD4+ cell counts less than 100 cells/mm3 never achieved absolute CD4+ cell counts comparable to the counts in patients starting enfuvirtide at CD4+ cell counts of 100 cells/mm3 or more. In 38.3% of patients achieving an undetectable HIV RNA level, a mean CD4+ cell count increase of 185 cells/mm3 was observed. An unexpected finding was that a mean CD4+ cell count increase of 76 cells/mm3 occurred in 61.7% of patients not achieving complete viral suppression. Conclusions: Immunologic benefits were observed in subjects continuing enfuvirtide plus a PBR irrespective of baseline CD4+ cell count, complete viral suppression, or antiretroviral susceptibility data. Dala suggest that initiation of enfuvirtide at CD4+ cell counts greater than 100 celis/mm3 may be immunologically advantageous and independent of complete virologic response.

scholarly journals Effect of Macrolide Prophylactic Therapy on AIDS-Defining Conditions and HIV-Related Mortality

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S59-S59
Author(s):  
Mark Kristoffer Pasayan ◽  
Mary Lorraine Mationg ◽  
David Boettiger ◽  
Wilson Lam ◽  
Fujie Zhang ◽  
...  
Keyword(s):  
Sensitivity Analyses ◽  
Immune Recovery ◽  
Combination Antiretroviral Therapy ◽  
Cd4 Counts ◽  
Art Initiation ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Cd4 Cell ◽  
The Impact ◽  
Related Mortality

Abstract Background Mycobacterium avium–intracelllulare complex (MAC) prophylaxis is recommended for patients with CD4 counts of &lt; 50 cells/mm3. With the significant decrease in incidence of disseminated MAC infection and the effective immune recovery due to the availability of combination antiretroviral therapy (ART), the benefits of giving MAC prophylaxis were investigated. This study examined the impact of macrolide prophylaxis on AIDS-defining conditions and HIV-associated mortality in a cohort of HIV-infected patients on ART. Methods TREAT Asia HIV Observational Database (TAHOD) patients aged ≥18 years with a CD4 count &lt; 50 cells/mm3 at ART initiation were included. The effect of macrolide prohylaxis on HIV-associated mortality or an AIDS event (as a combined outcome) and HIV-associated mortality alone were evaluated using competing risk regression. Sensitivity analysis was conducted to assess whether results were consistent in patients with a CD4 &lt; 100 cells/mm3 at ART initiation. Results Of 1,345 eligible patients (78% male with median age at ART initiation of 34.8 years), 10.6% received macrolide prophylaxis. The rates of the combined outcome and HIV-associated mortality per 100 patient years were 7.35 [95% confidence interval (CI): 6.04–8.95] and 3.14 (95% CI: 2.35–4.19), respectively. After adjusting for possible confounders, macrolide use was associated with a significantly decreased risk of HIV-associated mortality (HR 0.10, 95% CI: 0.01–0.80, P = 0.031) but not the combined outcome (HR 0.86, 95% CI: 0.32–2.229, P = 0.764). Sensitivity analyses showed that, among patients with a CD4 &lt; 100 cells/ mm3 at ART initiation, these results were consistent. Conclusion Macrolide prophylaxis is associated with significantly improved survival among Asian HIV-infected patients with very low CD4 cell counts. The benefits of giving macrolide prophylaxis remain despite the availability of effective ART. Disclosures All authors: No reported disclosures.

Statistical analysis of AZT effect on CD4 cell counts in HIV disease

1996 ◽  
pp. 194-196
Author(s):  
A.J. McNeil ◽  
S.M. Gore ◽  
R.P. Brettle ◽  
A.G. Bird
Keyword(s):  
Statistical Analysis ◽  
Hiv Disease ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Cd4 Cell

scholarly journals Virological and Immunological Aspects of AIDS Pathogenesis

1994 ◽  
Vol 5 (suppl e) ◽  
pp. 13E-18E
Author(s):  
Brian Conway ◽  
Francisco J Diaz-Mitoma
Keyword(s):  
Disease Progression ◽  
Proviral Load ◽  
Current Therapy ◽  
Cd4 Cells ◽  
Immune Disease ◽  
Large Variability ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Viral Phenotype ◽  
Cd4 Cell

The most common and serious problem associated with long term antiretroviral therapy is waning efficacy over time. To date. a number of studies has suggested an association between drug resistance and clinical deterioration. However. a precise causal relationship has yet to be demonstrated. In a large American clinical trial. resistance to zidovudine (ZDV) was predictive of subsequent disease progression if this therapy was continued. Surprisingly. this was also predictive of deterioration if therapy was changed to didanosine (ddl). This suggests that other factors (perhaps virological and immunological) which may be present in addition to resistance. were as important (if not more so) in predicting clinical outcomes. It is likely that viral load. resistance. viral phenotype and alterations in immune function interact in this regard. Proper· studies may allow us to determine a “threshold” for a composite virological and immunological parameter beyond which disease progression will occur. As more antiretroviral agents become available. we will be in a position to intervene to “improve” laboratory markers and monitor them prospectively. potentially to maintain clinical latency for an indefinite period of time. In the authors' laboratories, a quantitative polymerase chain reaction assay for the evaluation of circulating proviral load has been developed. In an initial study of 70 patients. proviral load/ 106CD4 cells was clearly associated with the severity of immune disease. with up to 9.6% of cells being infected in subjects with CD4 cell counts below 200/µL. However. large variability in proviral load among individuals with comparable or dissimilar CD4 cell counts precludes the use of this measurement as an individual marker of the severity of immune disease. More recent work evaluated the combined use of proviral load (expressed as a dichotomous variable based on values above or below one copy/a03CD4 cells) and resistance in a prospective fashion. In five patients with high proviral loads and isolates resistant to their current therapy. a mean decrease of 72 CD4 cells/µL was observed over 12 months of observation. In contrast. in six patients with low proviral loads and sensitive isolates. there was a mean increase of 43 CD4 cells/µL. It appears that virological markers are associated with immune disease progression in this small cohort of patients. The association appears most marked when the two virological parameters are considered together rather than individually. The association is not always a tight one. and this may relate to a number of unmeasured factors. including viral phenotype. plasma viremia. and the immune response to HIV infection. Additional work incorporating these parameters into analysis is currently underway in the authors’ centre.

scholarly journals Predictive factors of progression to severe COVID-19

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 805-814
Author(s):  
Yi-Hong Zhou ◽  
Huan Li ◽  
Yuan-Yuan Qin ◽  
Xiao-Feng Yan ◽  
Yan-Qiu Lu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Creatine Kinase ◽  
T Cell ◽  
Early Diagnosis ◽  
Disease Progression ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
The Difference ◽  
Cd4 Cell

AbstractAimEarly diagnosis and treatment are crucial for the survival of severe Coronavirus Disease 2019 (COVID-19) patients, but data with regard to risk factors for disease progression from milder COVID-19 to severe COVID-19 remain scarce.MethodsWe conducted a retrospective analysis on 116 patients.ResultsThree factors were observed to be independently associated with progression to severe COVID-19 during 14 days after admission: (a) age 65 years or older (hazard ratio [HR] = 8.456; 95% CI: 2.706–26.426); (b) creatine kinase (CK) ≥ 180 U/L (HR = 3.667; 95% CI: 1.253–10.733); and (c) CD4+ T-cell counts <300 cells/µL (HR = 4.695; 95% CI: 1.483–14.856). The difference in rates of severe COVID-19 development was found to be statistically significant between patients aged 65 years or older (46.2%) and those younger than 65 years (90.2%), between patients with CK ≥ 180 U/L (55.6%) and those with CK < 180 U/L (91.5%), and between patients with CD4+ T-cell counts <300 cells/µL (53.8%) and those with CD4+ cell counts ≥300 cells/µL (83.2%).ConclusionsAge ≥ 65 years, CK ≥ 180 U/L, and CD4+ T-cell counts <300 cells/µL at admission were risk factors independently associated with disease progression to severe COVID-19 during 14 days after admission and are therefore potential markers for disease progression in patients with milder COVID-19.

scholarly journals High Rates of Drug-induced Liver Injury in People Living With HIV Coinfected With Tuberculosis (TB) Irrespective of Antiretroviral Therapy Timing During Antituberculosis Treatment: Results From the Starting Antiretroviral Therapy at Three Points in TB Trial

2019 ◽  
Vol 70 (12) ◽  
pp. 2675-2682 ◽  
Author(s):  
Kogieleum Naidoo ◽  
Razia Hassan-Moosa ◽  
Philile Mlotshwa ◽  
Nonhlanhla Yende-Zuma ◽  
Dhineshree Govender ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Liver Injury ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Art Initiation ◽  
Tb Treatment ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Cd4 Cell ◽  
Early Late

Abstract Background New onset or worsening drug-induced liver injury challenges coinfected patients on antiretroviral therapy (ART) initiation during antituberculosis (TB) treatment. Methods Post hoc analysis within a randomized trial, the Starting Antiretroviral Therapy at Three Points in Tuberculosis trial, was conducted. Patients were randomized to initiate ART either early or late during TB treatment or after TB treatment completion. Liver enzymes were measured at baseline, 6-month intervals, and when clinically indicated. Results Among 642 patients enrolled, the median age was 34 years (standard deviation, 28–40), and 17.6% had baseline CD4+ cell counts &lt;50 cells/mm3. Overall, 146/472 patients (52, 47, and 47: early, late, and sequential arms) developed new-onset liver injury following TB treatment initiation. The incidence of liver injury post-ART initiation in patients with CD4+ cell counts &lt;200 cells/mm3 and ≥200 cells/ mm3 was 27.4 (95% confidence interval [CI], 18.0–39.8), 19.0 (95% CI, 10.9–30.9), and 18.4 (95% CI, 8.8–33.8) per 100 person-years, and 32.1 (95% CI, 20.1–48.5), 11.8 (95% CI, 4.3–25.7), and 28.2 (95% CI, 13.5–51.9) per 100 person-years in the early, late integrated, and sequential treatment arms, respectively. Severe and life-threatening liver injury occurred in 2, 7, and 3 early, late, and sequential treatment arm patients, respectively. Older age and hepatitis B positivity predicted liver injury. Conclusions High incidence rates of liver injury among cotreated human immunodeficiency virus (HIV)–TB coinfected patients were observed. Clinical guidelines and policies must provide guidance on frequency of liver function monitoring for HIV–TB coinfected patients.

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