The relationships between the HIV test interval, demographic factors and HIV disease progression

Individuals developing an HIV seroconversion illness may experience rapid disease progression. Information on seroconversion illness is rarely collected in most cohort studies; thus the aim of this study was to assess the value of the HIV test interval (the time between last negative and first positive HIV tests) as a proxy for seroconversion illness. Among 8229 seroconverters, test intervals ranged from 0-5282 days, and varied by gender, risk group, age and calendar year of seroconversion. Those with intervals less than or equal to 31 days had an increased hazard of AIDS (RH 1.42, P = 0.07), which was reduced slightly after adjusting for baseline factors, calendar year of follow-up, treatment and the declining CD4 count, but there was no effect on survival. Thus, it appears that if information on acute seroconversion illness is not available, then analyses of progression to AIDS in seroconverter studies could use a short test interval as a proxy measure

THE EFFECT OF CMV INFECTION ON PROGRESSION OF HUMAN-IMMUNODEFICIENCY-VIRUS DISEASE IN A COHORT OF HEMOPHILIC MEN FOLLOWED FOR UP TO 13 YEARS FROM SEROCONVERSION

The effect of prior infection with cytomegalovirus (CMV) on progression of HIV disease in a cohort of 111 men with haemophilia was studied after 13 years followup. The relative hazards associated with CMV positivity on progression to AIDS, death and a CD4 count of 0.05 x 10(9)/l were 2.28, 2.42 and 2.34, respectively. CMV seropositive patients were significantly older than the seronegative and this was controlled for by using a Cox proportional hazards model. The relative hazards for the three endpoints decreased to 1.89, 1.82 and 1.93 respectively and were marginally non-significant (P = 0.05, 0.08 and 0.08 for the three endpoints respectively). We conclude that this cohort continues to show evidence of a 'co-factor' effect associated with prior infection with CMV which is confounded by age but not completely explained by age differences. The potential biological significance of these results is discussed in the context of recent controlled clinical trials which show a survival benefit from long-term high-dose acyclovir, a drug with activity in vivo against CMV and other herpesviruses

The rate of CD4 decline as a determinant of progression to AIDS independent of the most recent CD4 count

The data of two cohort studies of HIV-infected individuals were used to examine whether the rate of CD4 decline is a determinant of HIV progression, independent of the most recent CD4 count. Time from seroconversion to clinical AIDS was the main outcome measure. Rates of CD4 decline were estimated using the ordinary least squares regression method. AIDS incidences were compared in individuals who had previously experienced either a steeper or a less steep rate of CD4 decline. Cox proportional hazards model including a time-dependent covariate for the rate of CD4 decline was performed. The rate of prior CD4 decline was significantly associated with the risk of developing AIDS independently from the most recent CD4 count, with a 2 % increase in hazard of AIDS (P < 0.01) for a difference of 10 cells/mm(3) in the estimated yearly drop in CD4 count. This finding gives scientific credit to the belief that individuals with a prior steeper CD4 decline consistently have a higher subsequent risk of developing AIDS than those with a less steep prior decline

Cardiovascular disease in HIV patients: recent advances in predicting and managing risk

Introduction: Cardiovascular disease (CVD) is one of the leading causes of mortality in virally suppressed people living with HIV (PLWH) and with an ageing population, is likely to become one of the leading challenges in maintaining good health outcomes in HIV infection. However, factors driving risk of CVD in PLWH are multiple and may be different from those of the general population, raising challenges to predicting and managing CVD risk in this population. / Areas covered: In this review, we examine the relevant data regarding CVD in HIV infection including that on CVD prevalence, pathogenesis and contributing factors. We review the data regarding CVD risk prediction in PLWH and summarise factors, both general and HIV specific, that may influence CVD risk in this population. And finally we discuss appropriate management of CVD risk in PLWH and explore potential therapeutic pathways which may mitigate CVD risk in the future in this population. / Expert opinion: Following a comprehensive review of CVD risk in PLWH, we give our opinion on the primary issues in risk prediction and management of CVD in HIV infected individuals and discuss the future direction of CVD management in this population

Natural history and outcome in systemic AA amyloidosis

BACKGROUND:Deposition of amyloid fibrils derived from circulating acute-phase reactant serum amyloid A protein (SAA) causes systemic AA amyloidosis, a serious complication of many chronic inflammatory disorders. Little is known about the natural history of AA amyloidosis or its response to treatment.METHODS:We evaluated clinical features, organ function, and survival among 374 patients with AA amyloidosis who were followed for a median of 86 months. The SAA concentration was measured serially, and the amyloid burden was estimated with the use of whole-body serum amyloid P component scintigraphy. Therapy for inflammatory diseases was administered to suppress the production of SAA.RESULTS:Median survival after diagnosis was 133 months; renal dysfunction was the predominant disease manifestation. Mortality, amyloid burden, and renal prognosis all significantly correlated with the SAA concentration during follow-up. The risk of death was 17.7 times as high among patients with SAA concentrations in the highest eighth, or octile, (greater/equal 155 mg per liter) as among those with concentrations in the lowest octile (< 4 mg per liter); and the risk of death was four times as high in the next-to-lowest octile (4 to 9 mg per liter). The median SAA concentration during follow-up was 6 mg per liter in patients in whom renal function improved and 28 mg per liter in those in whom it deteriorated (P < 0.001). Amyloid deposits regressed in 60% of patients who had a median SAA concentration of less than 10 mg per liter, and survival among these patients was superior to survival among those in whom amyloid deposits did not regress (P=0.04).CONCLUSIONS:The effects of renal dysfunction dominate the course of AA amyloidosis, which is associated with a relatively favorable outcome in patients with SAA concentrations that remain in the low-normal range (< 4 mg per liter)

Multimorbidity patterns in people with HIV

PURPOSE OF REVIEW: With the progressive aging of populations of people with HIV (PWH), multimorbidity is increasing. Multimorbidity patterns, that is groups of comorbidities that are likely to co-occur, may suggest shared causes or common risk factors. We review the literature regarding multimorbidity patterns identified with data-driven approaches and discuss the methodology and potential implications of the findings. RECENT FINDINGS: Despite the substantial heterogeneity in the methods used to identify multimorbidity patterns, patterns of mental health problems, cardiovascular diseases, metabolic disorders and musculoskeletal problems are consistently reported in the general population, with patterns of mental health problems, cardiovascular diseases or metabolic disorders commonly reported in PWH. In addition to these, patterns of lifestyle-related comorbidities, such as sexually transmitted diseases, substance use (alcohol, recreational drugs and tobacco smoking) or their complications, seem to occur among PWH. SUMMARY: Multimorbidity patterns could inform the development of appropriate guidelines for the prevention, monitoring and management of multiple comorbidities in PWH. They can also help to generate new hypotheses on the causes underlying previously known and unknown associations between comorbidities and facilitate the identification of risk factors and biomarkers for specific patterns

How have guidelines on when to start antiretroviral therapy affected survival of people living with HIV infection?

Purpose of review: Until recently, conflicting data led to discrepancies in guideline recommendation on ‘when to start’ antiretroviral therapy (ART) in asymptomatic HIV infection. This review focuses on evidence underpinning guidelines over the past decade and recent randomized clinical trial data in this area, which definitively informed the debate. Recent findings: In 2015, the landmark START trial demonstrated clear clinical benefit in terms of a reduction in serious AIDS and non-AIDS-related events and death from any cause in HIV-positive individuals randomized to start ART with a CD4 count more than 500 cells/µl compared with deferring starting until CD4 count declined to 350 cells/µl. Further, randomized clinical trial data were also available from the Temprano trial in Côte D’Ivoire which also demonstrated a reduced risk of death associated with earlier ART initiation. Summary: Following the results of the START trial, guidelines that had previously set CD4 thresholds for treatment initiation were universally changed. This is likely to reduce mortality in people living with HIV who are diagnosed early and have immediate access to ART. However, unless HIV testing rates and ART coverage are increased globally, raising the threshold for initiation of ART in clinical guidelines may be of limited benefit in reducing mortality in HIV

CD4+:CD8+T Cell Ratio Normalization and the Development of AIDS Events in People with HIV Starting Antiretroviral Therapy

We identify factors associated with the normalization of the CD4+:CD8+ T cell ratio among UK Collaborative HIV Cohort study participants, and describe the association of the CD4+ and CD8+ T cell counts and the CD4+:CD8+ T cell ratio, with the risk of new AIDS events among individuals who achieve a suppressed viral load. Participants initiating combination antiretroviral therapy (cART) after 2006 with a CD4+:CD8+ T cell ratio 500 vs. ≤200 cells/mm3, adjusted hazard ratio (95% confidence interval): 7.93 (6.97–9.01)], low CD8+ T cell count [>1,150 vs. ≤500 cells/mm3: 0.18 (0.16–0.21)], and low CD4+:CD8+ T cell ratio [>0.8 vs. 500 vs. ≤200 cells/mm3: adjusted rate ratio 0.24 (0.16–0.34)] and CD4+:CD8+ T cell ratio [>0.8 vs. <0.2: 0.33 (0.21–0.52)] were independently associated with a new AIDS event. One third of study participants experienced ratio normalization after starting cART. CD4+ T cell count and CD4+:CD8+ T cell ratio are both individually associated with ratio normalization and the development of new AIDS events after cART

The association of HBV core promoter double mutations (A1762T and G1764A) with viral load differs between HBeAg positive and anti-HBe positive individuals: A longitudinal analysis

Background/Aims: Although there have been a few reports regarding the effect of basal core promoter (BCP) double mutations (A1762T and G1764A) on hepatitis B viral loads, the association remains uncertain. We aim to determine the association after controlling for HBeAg - a strong confounding factor.Methods: We selected randomly 190 individuals from a Chinese cohort of 2258 subjects for cross-sectional analysis and 56 of the 190 for longitudinal analysis of viral loads.Results: In multivariable analysis of the cross-sectional data, BCP double mutations are significantly associated with lower viral loads in HBeAg positive subjects but no difference was found in anti-HBe positive subjects. Triple mutations at nucleotide (nt) 1753, 1762 and 1764 and mutations between nt 1809 and 1817, precore stop mutation (nt 1896) and genotype are not associated with viral loads in either HBeAg or anti-HBe positive subjects. Analysis of the longitudinal data yielded similar results to the cross-sectional data. Viral loads differ significantly between individuals infected with wild-type and BCP double mutations prior to HBeAg seroconversion but this difference is lost after seroconversion.Conclusions: BCP double mutations are associated with lower viral loads in HBeAg positive individuals but have no effect on the viral loads of anti-HBe positive individuals. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved