Long-Term Patterns in CD4 Response Are Determined by an Interaction Between Baseline CD4 Cell Count, Viral Load, and Time: The Asia Pacific HIV Observational Database (APHOD)

Egger, Sam; Petoumenos, Kathy; Kamarulzaman, Adeeba; Hoy, Jennifer; Sungkanuparph, Somnuek; Chuah, John; Falster, Kathleen; Zhou, Jialun; Law, Matthew

doi:10.1097/qai.0b013e31819906d3

Cited by 45 publications

(48 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…38 Surprisingly, the patients in this study with samples in which hypermutation was detected exhibited higher mean (285,782 -437,662) and median viral load levels compared to patients with samples in which hypermutation was not detected (181,825 -343,618) ( Table 4). Because our results differed from others published in the literature, we divided our case series into patients with viral loads above and below100,000 RNA copies/ml.…”

Section: Hiv-1 Hypermutation and Viral Loads In Brazil 873contrasting

confidence: 54%

“…An HIV-1 viral load above 100,000 RNA copies/ml relates to a faster progression to AIDS. 38 In our case series, patients were divided into two groups for analysis, based on viral load values higher or lower than 100,000 RNA copies/ml. A total of 100 patients exhibited serum viral load values lower than 100,000 RNA copies/ml, 23% of which exhibited virus with hypermutation; 53 patients exhibited a viral load higher than 100,000 RNA copies/ml, 46.3% of which exhibited virus with hypermutation.…”

Section: Quantitative Analysismentioning

confidence: 99%

See 1 more Smart Citation

In VivoHIV-1 Hypermutation and Viral Loads Among Antiretroviral-Naive Brazilian Patients

Lima-Stein

Alkmim²,

Bizinoto³

et al. 2014

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

Hypermutation alludes to an excessive number of specific guanine-to-adenine (G- >A) substitutions in proviral DNA and this phenomenon is attributed to the catalytic activity of cellular APOBECs. Population studies relating hypermutation and the progression of infection by human immunodeficiency virus type 1 (HIV-1) have been performed to elucidate the effect of hypermutation on the natural course of HIV-1 infection. However, the many different approaches employed to assess hypermutation in nucleotide sequences render the comparison of results difficult. This study selected 157 treatment-naive patients and sought to correlate the hypermutation level of the proviral sequences in clinical samples with demographic variables, HIV-1 RNA viral load, and the level of CD4(+) T cells. Nested touchdown polymerase chain reaction (PCR) was performed with specific primers to detect hypermutation in the region of HIV-1 integrase, and the amplified sequences were run in agarose gels with HA-Yellow. The analysis of gel migration patterns using the k-means clustering method was validated by its agreement with the results obtained with the software Hypermut. Hypermutation was found in 31.2% of the investigated samples, and a correlation was observed between higher hypermutation levels and higher viral load levels. These findings suggest a high frequency of hypermutation detection in a Brazilian cohort, which can reflect a particular characteristic of this population, but also can result from the method approach by aiming at hypermutation-sensitive sites. Furthermore, we found that hypermutation events are pervasive during HIV-1 infection as a consequence of high viral replication, reflecting its role during disease progression.

show abstract

Section: Hiv-1 Hypermutation and Viral Loads In Brazil 873contrasting

confidence: 54%

Section: Quantitative Analysismentioning

confidence: 99%

In VivoHIV-1 Hypermutation and Viral Loads Among Antiretroviral-Naive Brazilian Patients

Lima-Stein

Alkmim²,

Bizinoto³

et al. 2014

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

show abstract

“…Although not directly comparable due to differing analysis populations, treatment outcome differences in the Asia-Pacific have been reported elsewhere [22]–[25]. Briefly, Egger et al reported a lower absolute mean difference of in mean CD4 cell counts [−47 to −7 cell/µL] in TAHOD compared to AHOD [23]. A follow-up study by Achhra et al concluded that this mean CD4 cell count difference translated to minimal clinical significance in terms of mortality and new AIDS-defining illness [22].…”

Section: Discussionmentioning

confidence: 99%

Rates and Factors Associated with Major Modifications to First-Line Combination Antiretroviral Therapy: Results from the Asia-Pacific Region

Wright¹,

Boyd

Yunihastuti

et al. 2013

PLoS ONE

Self Cite

View full text Add to dashboard Cite

BackgroundIn the Asia-Pacific region many countries have adopted the WHO’s public health approach to HIV care and treatment. We performed exploratory analyses of the factors associated with first major modification to first-line combination antiretroviral therapy (ART) in resource-rich and resource-limited countries in the region.MethodsWe selected treatment naive HIV-positive adults from the Australian HIV Observational Database (AHOD) and the TREAT Asia HIV Observational Database (TAHOD). We dichotomised each country’s per capita income into high/upper-middle (T-H) and lower-middle/low (T-L). Survival methods stratified by income were used to explore time to first major modification of first-line ART and associated factors. We defined a treatment modification as either initiation of a new class of antiretroviral (ARV) or a substitution of two or more ARV agents from within the same ARV class.ResultsA total of 4250 patients had 961 major modifications to first-line ART in the first five years of therapy. The cumulative incidence (95% CI) of treatment modification was 0.48 (0.44–0.52), 0.33 (0.30–0.36) and 0.21 (0.18–0.23) for AHOD, T-H and T-L respectively. We found no strong associations between typical patient characteristic factors and rates of treatment modification. In AHOD, relative to sites that monitor twice-yearly (both CD4 and HIV RNA-VL), quarterly monitoring corresponded with a doubling of the rate of treatment modifications. In T-H, relative to sites that monitor once-yearly (both CD4 and HIV RNA-VL), monitoring twice-yearly corresponded to a 1.8 factor increase in treatment modifications. In T-L, no sites on average monitored both CD4 & HIV RNA-VL concurrently once-yearly. We found no differences in rates of modifications for once- or twice-yearly CD4 count monitoring.ConclusionsLow-income countries tended to have lower rates of major modifications made to first-line ART compared to higher-income countries. In higher-income countries, an increased rate of RNA-VL monitoring was associated with increased modifications to first-line ART.

show abstract

“…However, increases in CD4 counts vary by region [2,3], gender with a higher increase in CD4 count in women [3,4], the duration of antiretroviral therapy [3,5,6] and on the co-existence of other infections, particularly tuberculosis [7]. The greatest increases in CD4 count occur during the first year of ART initiation [4,5,8,9,10], especially in patients with low baseline CD4 count [11]. However patients with low CD4 count are more likely to take longer to return to normal CD4 count levels [5], and may remain at increased risk of opportunistic infection hence morbidity [12].…”

Section: Introductionmentioning

confidence: 99%

Among Patients with Sustained Viral Suppression in a Resource-Limited Setting, CD4 Gains Are Continuous Although Gender-Based Differences Occur

et al. 2013

View full text Add to dashboard Cite

IntroductionThere is conflicting data on long-term CD4 immune recovery after combination antiretroviral therapy (ART) in resource-limited settings. Virologic suppression is rarely documented in cohorts from sub-Saharan Africa so objective evidence of adherence is biologically unsubstantiated. We sought to investigate long-term patterns of immune recovery in Ugandan patients on ART with sustained viral suppression.MethodsA prospective cohort of patients starting ART between April, 2004 and April, 2005 at the Infectious Diseases Institute with sustained viral suppression (viral load ≤400 copies/ml at month 6 and 12) while on first-line ART. Propensity scores were used to adjust for treatment allocation (nevirapine or efavirenz) at ART initiation. Data were analyzed using Kaplan Meier methods and cross-sectional time series regression.ResultsThree hundred and fifty-six patients were included in the analysis.71.6% were female, 87% in WHO stage 3 or 4, median age was 37 years, (IQR:32–43), and median CD4 count was 108 cells/µL, (IQR:35–174) at ART start. At multivariable analysis, lower immune recovery (measured by change in CD4 from ART start at each time interval) was associated with male-gender (-59, 95% CI: 90, -28, P<0.001), baseline CD4 count of 101–200 cells/µL (-35, 95% CI: 62, -9, P=0.009) and >200 (-64, 95% CI: 101, -26, P=0.001), and use of AZT at baseline (-47, 95% CI: -74, -20, P=0.001). Median time to reach >400 cells/µL was longer in males (197.4 weeks, IQR:119.9–312.0), compared to females (144.7 weeks, IQR:96.6–219.7, P<0.001). The cumulative probability of attaining CD4 >400 cells/µL over 7 years was higher in females compared to males (P<0.001).ConclusionsThere was long-term, continuous, immunologic recovery up to 7 years after ART initiation in an urban Ugandan cohort. Virologically suppressed women had better sustained immune recovery than men. Men take longer to immune reconstitute and have a lower probability of reaching a CD4 cell count >400 cells/µL. The biologic mechanisms of these gender differences need further exploration.

show abstract

Long-Term Patterns in CD4 Response Are Determined by an Interaction Between Baseline CD4 Cell Count, Viral Load, and Time: The Asia Pacific HIV Observational Database (APHOD)

Cited by 45 publications

References 42 publications

In VivoHIV-1 Hypermutation and Viral Loads Among Antiretroviral-Naive Brazilian Patients

In VivoHIV-1 Hypermutation and Viral Loads Among Antiretroviral-Naive Brazilian Patients

Rates and Factors Associated with Major Modifications to First-Line Combination Antiretroviral Therapy: Results from the Asia-Pacific Region

Among Patients with Sustained Viral Suppression in a Resource-Limited Setting, CD4 Gains Are Continuous Although Gender-Based Differences Occur

Contact Info

Product

Resources

About