Updated CD4 Research Articles

1573. Viral Blips While on Antiretroviral Therapy are Associated with Virologic Failure

Abstract Background Blips in HIV viral load (VL) while on antiretroviral therapy (ART) are of unclear clinical significance. In this study, we examined the association between blips and virologic failure (VF). Methods We used data from the US Military HIV Natural History Study (NHS) cohort. Included participants were diagnosed with HIV after 2006, had been on ART for ≥ 6months, and had ≥3 VLs recorded and measured using an assay with a lower limit of detection of < 50 copies/mL. VF was defined as two consecutive VLs ≥ 200 copies/mL spanning 90 days or a single VL ≥1000 copies/mL. Blips were defined as VL of 51-999 copies/mL, that were preceded and followed by a VL ≤ 50 copies/mL and were differentiated by magnitude as low-level (VL 51-199 copies/mL) or high-level (200-999 copies/mL). Detectable VLs that did not meet criteria for VF or blips were grouped as low-level viremia (LLV; 51-199 copies/mL), and higher low-level viremia (hLLV; 200-999 copies/mL). Cox proportional hazards models adjusted for demographic characteristics, time updated CD4 counts, ART, and viral load were used. Hazard ratios and 95% confidence intervals are presented. Results A total of 988 participants (median age 34.1 years, 96.7% male, 41.7% African American) were included, of which 55 (5.6%) experienced VF (Table 1). While 191 participants (19.3%) experienced blips, it was the highest VL status in 146 (14.8%) (Table 2). Having blips and low-level viremia was associated with increasing hazard of VF, graded by type and level of viremia (low-level blip 1.86 [1.10 – 3.14]; high-level blip 3.56 [1.13 – 11.18]; LLV 4.10 [3.06-5.51]; hLLV 10.51 [6.28-17.61]. Other factors associated with VF were African American race and higher VL at ART initiation. Whereas higher CD4 counts, and use of integrase strand transfer inhibitors (relative to Non-Nucleoside Reverse Transcriptase inhibitors) were protective (Table 3). Conclusion Detectable viremia, including blips, are associated with an increased risk of VF. The magnitude of the viremia appears important with dose-response-type impact (i.e., viral loads >200 copies/mL having a greater hazard of VF). These findings suggest that individuals with viral blips at a minimum should undergo evaluation for medication adherence and may benefit from more frequent VL monitoring. Disclosures All Authors: No reported disclosures

Racial, ethnic, and gender disparities in hospitalizations among persons with HIV in the United States and Canada, 2005-2015.

To examine recent trends and differences in all-cause and cause-specific hospitalization rates by race, ethnicity, and gender among persons with HIV (PWH) in the United States and Canada. HIV clinical cohort consortium. We followed PWH at least 18 years old in care 2005-2015 in six clinical cohorts. We used modified Clinical Classifications Software to categorize hospital discharge diagnoses. Incidence rate ratios (IRR) were estimated using Poisson regression with robust variances to compare racial and ethnic groups, stratified by gender, adjusted for cohort, calendar year, injection drug use history, and annually updated age, CD4+, and HIV viral load. Among 27 085 patients (122 566 person-years), 80% were cisgender men, 1% transgender, 43% White, 33% Black, 17% Hispanic of any race, and 1% Indigenous. Unadjusted all-cause hospitalization rates were higher for Black [IRR 1.46, 95% confidence interval (CI) 1.32-1.61] and Indigenous (1.99, 1.44-2.74) versus White cisgender men, and for Indigenous versus White cisgender women (2.55, 1.68-3.89). Unadjusted AIDS-related hospitalization rates were also higher for Black, Hispanic, and Indigenous versus White cisgender men (all P < 0.05). Transgender patients had 1.50 times (1.05-2.14) and cisgender women 1.37 times (1.26-1.48) the unadjusted hospitalization rate of cisgender men. In adjusted analyses, among both cisgender men and women, Black patients had higher rates of cardiovascular and renal/genitourinary hospitalizations compared to Whites (all P < 0.05). Black, Hispanic, Indigenous, women, and transgender PWH in the United States and Canada experienced substantially higher hospitalization rates than White patients and cisgender men, respectively. Disparities likely have several causes, including differences in virologic suppression and chronic conditions such as diabetes and renal disease.

Hospitalization Rates and Causes Among Persons With HIV in the United States and Canada, 2005-2015.

To assess the possible impact of antiretroviral therapy improvements, aging, and comorbidities, we examined trends in all-cause and cause-specific hospitalization rates among persons with HIV (PWH) from 2005 to 2015. In 6 clinical cohorts, we followed PWH in care (≥1 outpatient CD4 count or HIV load [VL] every 12 months) and categorized ICD codes of primary discharge diagnoses using modified Clinical Classifications Software. Poisson regression estimated hospitalization rate ratios for calendar time trends, adjusted for demographics, HIV risk factor, and annually updated age, CD4, and VL. Among 28 057 patients (125 724 person-years), from 2005 to 2015, the median CD4 increased from 389 to 580 cells/µL and virologic suppression from 55% to 85% of patients. Unadjusted all-cause hospitalization rates decreased from 22.3 per 100 person-years in 2005 (95% confidence interval [CI], 20.6-24.1) to 13.0 in 2015 (95% CI, 12.2-14.0). Unadjusted rates decreased for almost all diagnostic categories. Adjusted rates decreased for all-cause, cardiovascular, and AIDS-defining conditions, increased for non-AIDS-defining infection, and were stable for most other categories. Among PWH with increasing CD4 counts and viral suppression, unadjusted hospitalization rates decreased for all-cause and most cause-specific hospitalizations, despite the potential effects of aging, comorbidities, and cumulative exposure to HIV and antiretrovirals.

CD4 count and tuberculosis risk in HIV-positive adults not on ART: a systematic review and meta-analysis.

BackgroundCD4 cell count in adults with human immunodeficiency virus (HIV) infection (PLHIV) not receiving antiretroviral therapy (ART) influences tuberculosis (TB) risk. Despite widespread use in models informing resource allocation, this relationship has not been systematically reviewed.MethodsWe systematically searched MEDLINE, Aidsinfo, Cochrane review database and Google Scholar for reports in English describing TB incidence stratified by updated CD4 cell count in cohorts of HIV-positive adults (age ≥15 years) not on ART (PROSPERO protocol no: CRD42016048888). Among inclusion criteria were: reporting precision for TB incidence, repeated CD4 measurements, and TB incidence reported for those not on ART or monotherapy. Study quality was assessed via the Newcastle-Ottawa tool for cohort studies. A Bayesian hierarchical model was fitted to estimate the pooled factor increase in TB incidence with respect to CD4 cell count decrement.ResultsA total of 1,555 distinct records were identified from which 164 full text articles were obtained. Common reasons for exclusion of full texts were: no valid TB incidence, no repeat CD4 measurements, and not reporting TB incidence by ART status. The seven studies included reported on 1,206 TB cases among 41,271 individuals, with a typical median follow-up of four years. Studies were generally rated as moderate or high quality. Our meta-analysis estimated a 1.43 (95% credible interval: 1.16–1.88)-fold increase in TB incidence per 100 cells per mm3 decrease in CD4 cell count.DiscussionOur analysis confirms previous estimates of exponential increase in TB incidence with declining CD4 cell count in adults, emphasizing the importance of early ART initiation to reduce TB risk in PLHIV.

Late initiation of combination antiretroviral therapy in Canada: a call for a national public health strategy to improve engagement in HIV care.

IntroductionCombination antiretroviral therapy (ART) significantly decreases morbidity, mortality and HIV transmission. We aimed to characterize the timing of ART initiation based on CD4 cell count from 2000 to 2012 and identify factors associated with late initiation of treatment.MethodsParticipants from the Canadian Observational Cohort (CANOC), a multi-site cohort of HIV-positive adults initiating ART naively after 1 January 2000, in three Canadian provinces (British Columbia, Ontario and Québec) were included. Late initiation was defined as a CD4 count <200 cells/mm3 or an AIDS-defining illness before ART initiation (baseline). Temporal trends were assessed using the Cochran–Armitage test, and independent correlates of late initiation were identified using logistic regression.ResultsIn total, 8942 participants (18% female) of median age 40 years (Q1–Q3 33–47) were included. The median baseline CD4 count increased from 190 cells/mm3 (Q1–Q3 80–320) in 2000 to 360 cells/mm3 (Q1–Q3 220–490) in 2012 (p<0.001). Overall, 4274 participants (48%) initiated ART with a CD4 count <200 cells/mm3 or AIDS-defining illness. Late initiation was more common among women, non-MSM, older individuals, participants from Ontario and BC (vs. Québec), persons with injection drug use (IDU) history and individuals starting ART in earlier calendar years. In sub-analysis exploring recent (2008 to 2012) predictors using an updated CD4 criterion (<350 cells/mm3), IDU and residence in BC (vs. Québec) were no longer significant correlates of late initiation.ConclusionsThis analysis documents increasing baseline CD4 counts over time among Canadians initiating ART. However, CD4 counts at ART initiation remain below contemporary treatment guidelines, highlighting the need for strategies to improve earlier engagement in HIV care.

Temporal Association Between Incident Tuberculosis and Poor Virological Outcomes in a South African Antiretroviral Treatment Service

Introduction:The temporal relationship between incident tuberculosis (TB) and virological outcomes during antiretroviral therapy (ART) is poorly defined. This was studied in a cohort in Cape Town, South Africa.Methods:Data regarding TB diagnoses, ART regimens, and 4-monthly updated viral load (VL) and CD4 count measurements were extracted from a prospectively maintained database. Rates of virological breakthrough (VL > 1000 copies/mL) and failure (VL > 1000 copies/mL on serial measurements) following initial VL suppression were calculated. Poisson models were used to calculate incidence rate ratios (IRRs) and identify risk factors for these virological outcomes.Results:Incident TB was diagnosed in 391 (28.5%) of 1370 patients during a median of 5.2 years follow-up. Five hundred seventy-eight episodes of virological breakthrough and 231 episodes of virological failure occurred, giving rates of 10.0 episodes per 100 person-years and 4.0 episodes per 100 person-years, respectively. In multivariate analyses adjusted for baseline and time-updated risk factors, TB was an independent risk factor for adverse virological outcomes. These associations were strongly time dependent; the 6-month period following diagnosis of incident TB was associated with a substantially increased risk of virological breakthrough (IRR: 2.3, 95% confidence interval: 1.7 to 3.2) and failure (IRR: 2.6, 95% confidence interval: 1.6 to 4.3) compared with time without a TB diagnosis. Person-time preceding TB diagnosis or more than 6 months after a TB diagnosis was not associated with poor virological outcomes.Conclusions:Incident TB during ART was strongly associated with poor virological outcomes during the 6-month period following TB diagnosis. Although underlying mechanisms remain to be defined, patients with incident TB may benefit from virological monitoring and treatment adherence support.

Response to antiretroviral therapy

We investigated the association between immune response and mortality in four HIV African programs supported by Médecins Sans Frontières. Multicentric retrospective cohort study. All antiretroviral therapy (ART) naive adults (>15 years) who initiated therapy between March 2001 and November 2010 and receiving therapy for 9 months or more were included. We described the evolution of mortality over time. Mixed Poisson models were used to assess the effect of updated CD4 cell counts and other potential risk factors on mortality. A total of 24 037 patients, of which 68% were women, contributed 69 516.2 person-years of follow-up. At ART initiation, 5718 patients (23.7%) were classified as WHO clinical stage 4, 1587 (6.6%) had a BMI below 16 kg/m and 2568 (10.7%) had CD4 cell count below 50 cells/μl. A total of 568 (2.4%) deaths were recorded during the study period. In the CD4 response categories 500 cells/μl or more, 350-499, 200-349, 50-199 cells/μl and less than 50 cells/μl, unadjusted mortality rates were 0.36; 0.58; 0.88; 1.91 and 7.43 per 100 person-years, respectively. In multivariate analysis, higher mortality was observed in patients with CD4 response levels 350-499 cells/μl [adjusted hazard ratio (aHR) 1.70, 95% confidence interval (CI) 1.26-2.30] and for those between 200-349 (aHR 2.56; 95% CI 1.93-3.38), compared to those with 500 cells/μl or more. The observed higher survival of patients with a CD4 response to ART higher than 500 cells/μl supports the need of further research to evaluate the individual benefit of initiating ART at higher CD4 levels in sub-Saharan Africa.

Tuberculosis in Patients Receiving Antiretroviral Treatment: Incidence, Risk Factors, and Prevention Strategies

To determine tuberculosis (TB) incidence rates and risk factors among individuals receiving antiretroviral treatment (ART). Observational cohort in Johannesburg, South Africa. Incident TB was classified as early (less than 6 months of ART) or late (greater than 6 months of ART) incident TB. CD4 cell counts, viral load, body mass index, and hemoglobin were measured 6-monthly. Hazard ratios for factors associated with early and late incident TB were assessed using Cox proportional hazards regression. During 13,416 person-years of follow-up, 501 TB cases occurred among 7536 individuals, corresponding to a 10% risk in the first 4 years of ART and an overall incidence rate of 4.2 cases/100 person-years. The highest incidence rate (21.7 per 100 person-years) was observed in the first 3 months of ART among people with CD4 count below 50 cells/mm3. Low baseline CD4 count, anemia, and low body mass index were the strongest risk factors for early incident TB. Low updated CD4 count, low updated body mass index, anemia, and high viral load on ART were strong risk factors for late incident TB. Severity of HIV disease and unfavorable response to ART are associated with early and late incident TB, respectively. Early ART initiation and intensified TB screening at ART initiation are crucial to reduce incident TB.

IL-2 therapy: potential impact of the CD4 cell count at initiation on clinical efficacy--results from the ANRS CO4 cohort

We investigated why, despite its beneficial effect on the CD4 cell count, IL-2 therapy had no clinical benefit as shown in the ESPRIT and SILCAAT trials. We focused on subgroups of patients defined according to CD4 cell counts at baseline and over time to assess the threshold above which IL-2 therapy was no longer beneficial in a large cohort of HIV-1 infected patients. Within the French Hospital Database on HIV, a total of 953 IL-2-treated patients were compared with 27 750 IL-2-untreated patients, matched for the date of enrolment, sex, age, and the baseline CD4 cell count and plasma HIV-1 RNA level. The risk of clinical progression, defined as the occurrence of a new AIDS-defining event or death, was studied with multivariable Cox proportional hazards models and Poisson regression models. We found no clinical benefit in patients starting IL-2 with CD4 count ≥200 cells/mm(3) [hazard ratio (HR) =1.13; 95% confidence interval (CI), 0.81-1.57], while a benefit was observed in patients with CD4 count <200 cells/mm(3) (HR=0.64; 95% CI, 0.48-0.86). The observed benefit was due to the risk reduction in the 100-350/mm(3) stratum of updated CD4 cell counts (relative rate=0.30; 95% CI, 0.09-1.03). Higher CD4 cell counts at enrolment and shorter follow-up with low to intermediate CD4 cell counts may explain why IL-2 therapy had no observed clinical benefit in the SILCAAT study. Our findings suggest that the benefit of IL-2 is restricted to a narrow range of CD4 cell counts, arguing against the use of IL-2 in HIV infection to reduce the risk of clinical events.

Short-term and long-term risk of tuberculosis associated with CD4 cell recovery during antiretroviral therapy in South Africa

To determine the short-term and long-term risks of tuberculosis (TB) associated with CD4 cell recovery during antiretroviral therapy (ART). Observational community-based ART cohort in South Africa. TB incidence was determined among patients (n = 1480) receiving ART for up to 4.5 years in a South African community-based service. Updated CD4 cell counts were measured 4-monthly. Person-time accrued within a range of CD4 cell count strata (CD4 cell strata) was calculated and used to derive CD4 cell-stratified TB rates. Factors associated with incident TB were identified using Poisson regression models. Two hundred and three cases of TB were diagnosed during 2785 person-years of observation (overall incidence, 7.3 cases/100 person-years). During person-time accrued within CD4 cell strata 0-100, 101-200, 201-300, 301-400, 401-500 and more than 500 cells/microl unadjusted TB incidence rates were 16.8, 9.3, 5.5, 4.6, 4.2 and 1.5 cases/100 person-years, respectively (P < 0.001). During early ART (first 4 months), adjusted TB rates among those with CD4 cell counts 0-200 cells/microl were 1.7-fold higher than during long-term ART (P = 0.026). Updated CD4 cell counts were the only patient characteristic independently associated with long-term TB risk. Updated CD4 cell counts were the dominant predictor of TB risk during ART in this low-resource setting. Among those with baseline CD4 cell counts less than 200 cells/microl, the excess adjusted risk of TB during early ART was consistent with 'unmasking' of disease missed at baseline screening. TB incidence rates at CD4 cell counts of 200-500 cells/microl remained high and adjunctive interventions are required. TB prevention would be improved by ART policies that minimized the time patients spend with CD4 cell counts below a threshold of 500 cells/microl.

Changing mortality risk associated with CD4 cell response to antiretroviral therapy in South Africa

To determine the relationship between mortality risk and the CD4 cell response to antiretroviral therapy (ART). Observational community-based ART cohort in South Africa. CD4 cell counts were measured 4 monthly, and deaths were prospectively ascertained. Cumulative person-time accrued within a range of updated CD4 cell count strata (CD4 cell-strata) was calculated and used to derive CD4 cell-stratified mortality rates. Patients (2423) (median baseline CD4 cell count of 105 cells/microl) were observed for up to 5 years of ART. One hundred and ninety-seven patients died during 3155 person-years of observation. In microltivariate analysis, mortality rate ratios associated with 0-49, 50-99, 100-199, 200-299, 300-399, 400-499 and at least 500 cells/microl updated CD4 cell-strata were 11.6, 4.9, 2.6, 1.7, 1.5, 1.4 and 1.0, respectively. Analysis of CD4 cell count recovery permitted calculations of person-time accrued within these CD4 cell-strata. Despite rapid immune recovery, high mortality in the first year of ART was related to the large proportion of person-time accrued within CD4 cell-strata less than 200 cells/microl. Moreover, patients with baseline CD4 cell counts less than 100 cells/microl had much higher cumulative mortality estimates at 1 and 4 years (11.6 and 16.7%) compared with those of patients with baseline counts of at least 100 cells/microl (5.2 and 9.5%) largely because of greater cumulative person-time at CD4 cell counts less than 200 cells/microl. Updated CD4 cell counts are the variable most strongly associated with mortality risk during ART. High cumicrolative mortality risk is associated with person-time accrued at low CD4 cell counts. National HIV programmes in resource-limited settings should be designed to minimize the time patients spend with CD4 cell counts less than 200 cells/microl both before and during ART.

Impact of Combined Anti-Retroviral Therapy on HIV-Associated Non-Hodgkin-Lymphoma - a Prospective European Multi-Cohort Study on Behalf of the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) Study Group

Background: Following its introduction in 1996, combination antiretroviral therapy (cART) has led to a substantial reduction in HIV-associated morbidity and mortality. The decline has, however, been less pronounced for non-Hodgkin lymphoma (NHL) than for other HIV-related complications, and NHL has become the most common cancer associated with HIV. Within the framework of a large prospective European multi-cohort project, the Collaboration of Observational HIV Epidemiological Research Europe (COHERE), we studied the incidence and risk factors for the development and survival of NHL in HIV-infected patients in the cART era.Methods: We analyzed the data of HIV- infected adult patients (aged >16 years) who were cART naïve at inclusion and started cART after 01.01.1998, at a time when cART had become well established and widely used in Europe. cART was defined as a regimen of at least 3 antiretroviral drugs. Patients had to have CD4 count measurements available before the start of cART and the diagnosis of NHL. Patients developing NHL before receiving cART (“not on cART”) and patients developing NHL while receiving cART (“on cART”) were analyzed separately. Both patients with Primary Brain Lymphoma (PBL) and systemic NHL were included in the analysis. Incidence rates were calculated based on the Poisson distribution; risk factors were estimated using crude and adjusted Weibull models, with random effects to account for heterogeneity between cohorts. Models with time varying covariates were used to explore the effects of CD4 cell counts and plasma HIV-RNA loads over time. Survival was estimated using Kaplan-Meier life table probabilities, with 95% confidence intervals (95% CI).Results: For the incidence analysis 56,305 patients from 22 cohort studies across Europe with 212,042 person-years at risk were evaluated. The incidence for NHL (both systemic NHL and PBL) in patients not on cART was 519 (95% CI 448 to 602) per 100,000 personyears compared to 229 (95% CI 208 to 252) per 100,000 person-years in those on cART. The corresponding rates for PBL were 57 (95% CI 36 to 89) per 100,000 person-years and 24 (95% CI 18 to 33) per 100,000 person years. In cART naïve patients risk factors for NHL were older age and low CD4 cell count nadirs. When included as time up-dated variables, high plasma HIV-1 RNA loads and low CD4 cell counts emerged as important risk factors. In patients receiving cART risk factors included low CD4 cell count nadirs, older age, and groups associated with HHV-8 infection, i.e. men having sex with men and patients with a previous diagnosis of Kaposi Sarcoma. Time up-dated HIV-1 RNA plasma concentration and CD4 cell count were also associated with developing NHL while on cART. For the survival analysis 847 NHL patients were eligible. Of those, 364 (43%) were cART naïve at diagnosis of NHL. After one year 66% (95% CI 63%–70%) of patients with systemic NHL and 54% (95% CI 43%–65%) of patients with PBL were alive. Risk factors for death were diagnosis of PBL, low CD4 cell count nadir and history of injection drug use.Conclusions: Combined anti-retroviral therapy reduces the risk of developing NHL. In the era of cART more advanced immunodeficiency is the dominant risk factors for developing NHL both in patients receiving and not receiving cART. Two thirds of patients diagnosed with HIV-related NHL other than PBL survive for longer than one year after diagnosis. Survival is poorer in patients diagnosed with PBL.

Time-updated CD4+ T lymphocyte count and HIV RNA as major markers of disease progression in naive HIV-1-infected patients treated with a highly active antiretroviral therapy: the Aquitaine cohort, 1996-2001.

In naive HIV-1 infected patients who start a highly active antiretroviral therapy (HAART), the relationship between time-updated CD4+ cell count, HIV RNA, and clinical progression (new AIDS-defining event or death) is incompletely understood. A 2-step statistical approach was adopted: first, modeling the evolution of the 2 markers taking into account left-censoring of HIV RNA and, second, studying their respective effect on clinical progression. The study sample consisted in 551 previously untreated patients of the Aquitaine Cohort who started their first HAART regimen between 1996 and 2000. During a median follow-up of 33 months, 46 patients experienced a new AIDS-defining diagnosis and 23 died. In multivariate survival analysis, time-updated CD4+ cell count (hazard ratio [HR] = 1.92 for 100 cells/mm3 lower, P < 10(-4) and HIV RNA (HR = 1.30 for 1 log(10) copies/mL higher, P = 0.04) on continuous scale were associated with clinical progression. When analyzing the effect of updated biomarkers using usual thresholds, the association with clinical progression was weaker for CD4+ but still significant (P = 0.007) whereas it remained only significant for updated HIV RNA above 4 log(10) copies/mL (P = 0.01). The prognostic information of updated HIV RNA adjusted on updated CD4+ is significant but depends on how the markers are taken into account. Clinical decisions and interpretation of clinical trial results must weigh the signification of each of these 2 biomarkers.

Is the time from HIV seroconversion a determinant of the risk of AIDS after adjustment for updated CD4 cell counts?

To evaluate the effect of time from seroconversion to a given CD4 cell count on progression to AIDS after that count after adjusting for updated CD4 cell counts. Using pooled data from 19 seroconverter cohorts, we examined the association between the time from a CD4 <500 cells/mm 3, (<350, <200) to the first AIDS-defining event and time from seroconversion to that CD4 threshold. We adjusted for age, gender, exposure category, and HIV test interval in Cox models stratified by cohort. We estimated the residual effect of time from seroconversion, adjusting for updated CD4 cell counts. A cause-specific competing-risks model was then used to evaluate this residual effect on progression to each AIDS-defining disease. Analyses were censored on December 31, 1995. Of 3825, 3006, and 1804 individuals reaching CD4 thresholds of 500, 350, and 200, respectively, 1274, 1192, and 985, respectively, developed AIDS. We found a significant effect of time from seroconversion on the risk of AIDS even after adjusting for updated CD4 counts. For individuals reaching a CD4 threshold of 350 cells/mm 3, a 1-year increase from seroconversion was associated with an increase in risk of AIDS of 6% (3%-9%) ( p =.01). This effect appeared to be nonlinear. In the first 4 years, a 1-year increase from seroconversion was associated with an 11% increase in the risk of AIDS, but there was no apparent increase in risk after 4 years. The residual effect of time from seroconversion was significantly heterogeneous ( p =.002), with respect to the risk of individual AIDS-defining diseases. Findings were similar for CD4 thresholds of 500 and 200 cells/mm 3, respectively. We found a small, statistically significant, residual effect of time from seroconversion on the risk of AIDS. In practical terms, when considering an infected individual's risk of AIDS from a given CD4 cell count, there is little to be gained from knowing the time of seroconversion. However, this effect differs significantly among specific AIDS-defining diseases.

Is the Time From HIV Seroconversion a Determinant of the Risk of AIDS After Adjustment for Updated CD4 Cell Counts?

Is the Time From HIV Seroconversion a Determinant of the Risk of AIDS After Adjustment for Updated CD4 Cell Counts?

Natural history of serum HIV-1 RNA levels in 330 patients with a known date of infection. The SEROCO Study Group.

To describe the spontaneous course, before the introduction of highly active antiretroviral therapy (HAART), of HIV-1 RNA during the AIDS-free period of the disease. To assess the predictive value of changes in HIV-1 RNA levels. A total of 330 patients with a known date of infection followed in the SEROCO cohort. HIV-1 RNA levels (threshold, 200 copies/ml) were evaluated from 2243 frozen sera obtained from enrolment until the onset of AIDS or until February 1996. Lowess curves were used to describe the variations of viraemia during follow-up. A Cox regression model was used to assess the predictive value of early and updated CD4 cell count and viral load. In addition to a lower early viral load, patients who remained AIDS-free had, on average, a longer period of viral load decrease after infection (36 versus 18 months), followed by a slower viral load increase compared with those who progressed to AIDS. A true plateau-phase after the seroconversion period, lasting approximately 4 years, was identified only in patients who remained AIDS-free for at least 90 months. In multivariate analysis, both early viral load and later changes were significant predictors of progression to AIDS. A decrease in the CD4 cell count to less than 200 cells/microl and the onset of a group B condition remained significant predictors of progression. Our study extends to the early post-seroconversion phase the prognostic value of extracellular HIV-1 RNA levels. Moreover, our data suggest that, in most HIV-infected individuals, a progressive loss of control of viral replication arises during the early years of HIV-1 infection.

CD4 lymphocyte count as a predictor of the duration of highly active antiretroviral therapy-induced suppression of human immunodeficiency virus load.

The association between CD4 cell count and duration of virus load suppression was investigated in 558 patients in the Frankfurt HIV Clinic Cohort who had begun highly active antiretroviral therapy and who had virus load declines to </=500 copies/mL. The Kaplan-Meier method estimated viral rebound in 42.5% of patients by 24 weeks and in 64.3% by 84 weeks. Risk of viral rebound was independently associated with baseline and changes from baseline CD4 cell count. The achieved CD4 cell count was the most important factor for prediction of viral rebound (relative hazard, 5.4 for an updated CD4 cell count of <20 vs. >500 copies/mL; P=.0001). Baseline virus load was not associated with virus load rebound. Lower baseline CD4 cell counts were associated with increased risk of viral rebound; however, this risk was significantly reduced in persons with low baseline CD4 cell counts who experienced substantial increases in CD4 cell counts during follow-up.