Effect of early initiation of highly active antiretroviral therapy on CD4 cell count and HIV-RNA viral load trends within 24 months of the onset of acute retroviral syndrome

Objectives

The effect of starting highly active antiretroviral therapy (HAART) early after the onset of acute retroviral syndrome (ARS) on CD4 and HIV‐RNA trends was studied over a 2‐year follow‐up period.

Methods

Four groups of HIV‐infected patients stratified according to the time interval from ARS onset to HAART initiation and a control group of untreated patients were compared. Results The results indicated that the earlier the start of HAART, the faster was the rate of CD4 increase and HIV‐RNA decrease. However, this difference did not seem to persist at 24 months.

Conclusions

The optimal treatment strategy for HIV‐infected patients needs to be explored further.     

Factors associated with a reduced CD4 lymphocyte count response to HAART despite full viral suppression in the EuroSIDA study

Objectives

To describe the prevalence and risk factors of poor CD4 count rise despite a good virological response on highly active antiretroviral treatment (HAART).

Methods

The patients from the EuroSIDA study who started HAART with a baseline CD4 count of <350 cells/μL and where all viral load (pVL) measures remained below 500 HIV‐1 RNA copies/mL between 6 and 12 months after the start of HAART were included. The risk factors for poor CD4 count rise were analyzed by multiple regression.

Results

Seven hundred and eighty patients were included. A low CD4 count response was observed in 225 patients (29%). The risk factors for this condition were older age, lower CD4 count at baseline, higher increase from the nadir to baseline CD4 count and lower pVL at baseline. Patients taking ≥one drug from each of the three antiviral classes were more likely to have a good CD4 response but a minority of the study participants was taking this treatment regimen (3.1%) and the confidence interval was large.

Conclusions

A poor immune reconstitution despite a good virological control is frequent after initiation of HAART among patients with a baseline CD4 count of <350 cells/μL. The underlying mechanisms leading to this condition seems mainly driven by the age and the baseline immunological and virological status of the patients.

     

Short‐term antiretroviral therapy to prevent mother‐to‐child transmission is safe and results in a sustained increase in CD4 T‐cell counts in HIV‐1‐infected mothers*

Background

Short‐term antiretroviral therapy (START) to prevent mother‐to‐child transmission (MTCT) is currently recommended for all HIV‐1‐infected pregnant women. The objective of this study was to assess the effect on CD4 cell counts and viral load dynamics the withdrawal of START after birth could generate.

Methods

This was a 5‐year cohort study involving HIV‐1‐infected pregnant women who presented with CD4 counts >300 cells/μL and had received START to prevent MTCT.

Results

Seventy‐five pregnancies were assessed. In 24 cases, there was a history of antiretroviral therapy prior to prophylaxis. The median baseline CD4 count was 573 cells/μL. In 75% of cases, prophylaxis was started after 26.6 weeks of gestation. The median CD4 cell count increase over baseline during prophylaxis was 24.5%. In only five cases did HIV‐1 viral load remain detectable during prophylaxis. After START, CD4 cell counts did not drop significantly, and the HIV‐1 viral load plateau was near the baseline level. The estimated mean time for CD4 count to fall below 300 cells/μL was 3.5 years and was directly associated with high baseline CD4 cell count, as well as with CD4 increase after prophylaxis, whereas it was negatively correlated with previous use of antiretroviral (ARV) drugs and persistence of detectable HIV‐1 viral load during prophylaxis.

Conclusions

A potent, well‐tolerated prophylactic ARV regimen can improve CD4 cell counts during and after START. In women receiving such prophylaxis, there is a remarkable time interval for CD4 cell counts to drop to levels that indicate treatment.     

CD4 count and viral load time-courses in patients treated with highly active antiretroviral therapy and association with the CDC staging system

Objectives

The aim of the study was to analyse CD4 cell count and viral load dynamics in patients undergoing antiretroviral therapy and their association with the Centers for Disease Control and Prevention (CDC) classification system.

Methods

CD4 cell count and viral load were determined in 2982 patients who were classified according to clinical and immunological CDC stages. Measurements were carried out at baseline and at the 3rd, 6th and 12th months.

Results

Clear differences in the immunological and virological responses to therapy were observed depending on the CDC stage, with better results associated with less advanced stages. There was a marked parallelism in the CD4 cell count curves of the different CDC stages over the year of follow up, in both naïve and experienced patients, indicating that the increase in CD4 cell count at each time‐point was similar for all clinical and immunological CDC stages. However, as the baseline values were closely associated with CDC stage, the CD4 cell counts finally reached were clearly dependent on CDC stage. The highest virological responses were observed during the initial 3 months, particularly in naïve patients, but whereas naïve patients showed additional increases up to the 6th month experienced patients reached a plateau at the 3rd month. The CD4 increases were also higher during the initial 3 months but persisted during the year of follow‐up.

Conclusion

Both clinical and immunological CDC stages at baseline are highly predictive of the immunological and virological response to therapy, a finding that could have clinical implications.

     

Factors predicting the time for CD4 T-cell count to return to nadir in the course of CD4-guided therapy interruption in chronic HIV infection

OBJECTIVE: Our previous studies on CD4-guided therapy interruption (TI) showed that the durations of the first and second TIs were similar if antiretroviral therapy (ART) was resumed at a level of the CD4 cell count similar to or higher than the nadir CD4 T-cell count. Therefore, in a strategy of repeated CD4-guided TI, it is important to know which factors predict the time for the CD4 T-cell count to return to nadir (TRN). METHODS: From a cohort of 125 patients who interrupted ART, 92 patients who reached a CD4 T-cell count similar to the nadir count were included in the study. RESULTS: The median TRN was 12.3 months. In the multivariate analysis, younger age (P=0.011), lower pre-ART HIV RNA (P=0.022) and female gender (P=0.045) were associated with a longer TRN. After TI there were 11 clinical events in the group of patients whose nadir CD4 count was >200 cells/microL. Most of these events occurred when the TI was prolonged beyond the TRN. CONCLUSIONS: The factors predicting the TRN were age, HIV RNA pre-ART and gender. Resumption of therapy at a CD4 cell count similar to the nadir CD4 count appears to protect against the development of clinical events. Given the observational nature of this study, no conclusions can be drawn regarding the possible application of TI in clinical practice.     

Pregnancy may be followed by an inflexion of the immune reconstitution in HIV-infected women who receive antiretroviral drugs before conception

Background

Whether pregnancy has an impact on the evolution of CD4 cell counts in women treated with highly potent antiretrovirals before conception remains largely unknown.

Methods

Among patients enrolled in the ANRS CO8 (APROCO/COPILOTE) cohort, we selected all women aged between 18 and 50 years at initiation of combination antiretroviral therapy (cART). Slopes of CD4 cell counts during follow‐up were estimated using mixed longitudinal models with time‐dependent indicators for pregnancy and delivery.

Results

Of the 260 selected HIV‐infected women, a pregnancy occurred in 39 women in a median follow‐up time of 66 months. Women who became pregnant had higher CD4 cell count at baseline but this difference progressively lessened during follow‐up because they had a slower increase than women who did not become pregnant. The estimated slope of CD4 cell count decreased significantly from +2.3 cells/μL/month before pregnancy and in women who did not become pregnant to ?0.04 cells/μL/month after delivery (P=0.0003).

Conclusion

A significant increase in CD4 cell count may be preferable before pregnancy in women treated with cART, in order to overcome the evolution observed after pregnancy.