11th January Monge et al., Combined antiretroviral treatment in migrants in Europe

Timing of cART initiation in male and female migrants living with HIV in Western Europe: an observational cohort study (1997-2013).    AIDS

The Migrant Health Working Group on behalf of COHERE in EuroCoord aimed to evaluate differences in timing of combined antiretroviral treatment (cART) initiation by geographical origin in male and female HIV-positive patients in COHERE. They included 151 674 individuals (72.9% men) from Western Europe between January 1997 and March 2013, with known geographical origin and at least 1 CD4+ cell count measurement while cART-naïve.

Median CD4+ cell count falls far below 250 cells/ml in all groups and was lowest in sub-Saharan African (SSA: 161), Caribbean men (161) and in Asian women (185). Among men, the adjusted probability of cART initiation was lower in migrants compared with natives, but differences depended on initial CD4+ cell count. In women, no meaningful differences were observed between natives and most migrant groups. However, SSA women had a 31% higher probability of cART initiation when recruited at a CD4+ more than 500 cells/ml and 9% (4–14%) lower when recruited at CD4+ less than 100 cells/ml.

In conclusion, the study-results highlight late initiation of cART in the migrant population in Western Europe and differences in timing of cART initiation for some groups within migrant communities, especially for men. Addressing existing barriers to access HIV testing and care and ensuring universal and free access to cART is important to advance in the elimination of inequities and in the control of the HIV epidemic in Western Europe.


10th January Judd et al., Triple-class failure by age and perinatal HIV

Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe.    HIV Medicine

Judd et al. on behalf of COHERE in EuroCoord aimed to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection.

A total of 5’972 participants starting antiretroviral therapy (ART) from 1998, aged 500 HIV-1 RNA copies/mL despite ≥4 months of use.

The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall (17 vs. 8 weeks) and highest in perinatally infected participants aged 10–14 years (49 weeks). The cumulative proportion with TCVF 5 years after starting ART was 9.6% in participants with perinatally acquired infection and 4.7% in participants with heterosexually acquired infection. Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10–14 years, African origin, pre-ART AIDS, NNRTI based initial regimens, higher pre-ART viral load and lower pre-ART CD4.

In conclusion, for participants with perinatal HIV infection, these findings indicate the need to diagnose and start ART earlier in childhood, and adopt a strategic approach in ART selection to prevent the emergence of resistance. These measures may help children and adolescents achieve and sustain virological suppression as they approach adulthood.

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4th January Stirrup et al., Predictors of CD4 recovery following initiation of ART

Predictors of CD4 cell recovery following initiation of antiretroviral therapy among HIV-1 positive patients with well-estimated dates of seroconversion.     HIV Medicine

Stirrup et al. on behalf of CASCADE Collaboration in EuroCoord aimed to investigate factors that predict speed of recovery and long-term CD4 cell count in HIV-1 seroconverters initiating combination antiretroviral therapy (cART), and to quantify the influence of very early treatment initiation. They used data from the CASCADE multinational cohort collaboration of HIV-1 seroconverters and analysed pre- and post-treatment data of patients with seroconversion dates estimated January 2003 - March 2014 (n=7600).

The authors found that “true’ CD4 count at cART initiation was the strongest predictor of CD4 count beyond 3 years on cART. CD4 recovery was more rapid for patients in whom treatment was initiated within 4 months. For a given CD4 count, higher viral load (VL) at initiation was strongly associated with higher post-treatment CD4 recovery. Use of an integrase-inhibitor regimen at treatment initiation was found to be associated with a moderate improvement in post-treatment recovery in CD4 relative to the NNRTI regimen.

In conclusion, CD4 count at cART initiation is the most important factor in predicting post-treatment recovery, but VL provides substantial additional information. If cART is initiated in the first 4 months following seroconversion, recovery of CD4 counts appears to be more rapid. The finding that higher plasma VL at treatment initiation predicts more rapid CD4 cell recovers is maybe explained by some evidenced that higher VL levels are associated with sequestration of CD4 cells in lymphoid tissue and that this is associated with a more rapid initial increase in circulating CD4 cells following the initiation of cART.


3rd January Trickey et al., CD4:CD8 and CD8 as Markers for Mortality

CD4:CD8 ratio and CD8 count as prognostic markers for mortality in Human Immunodeficiency Virus–infected patients on antiretroviral therapy: The Antiretroviral Therapy Cohort Collaboration (ART-CC).    Clinical Infectious Diseases

Trickey et al. on behalf of the Antiretroviral Therapy Cohort Collaboration aimed to investigate whether the CD4:CD8 ratio or CD8 counts were independently associated with all-cause, AIDS, and non-AIDS mortality in patients treated with antiretroviral therapy (ART) with suppressed viral load and CD4 count >350 cells/μL For the analysis, the authors combined data from 13 European and North American cohorts participating in the Antiretroviral Therapy Cohort Collaboration.

During 276’526 person-years, 1’834 of 49’865 patients (3.7%) died (249 AIDS-related; 1’076 non-AIDS-defining; 509 unknown/unclassifiable deaths). There was little evidence that CD4:CD8 ratio was prognostic for all-cause mortality after adjustment for other factors: the adjusted hazard ratio (aHR) for lower vs middle tertile was 1.11. The association of CD8 count with all-cause mortality was U-shaped with a higher mortality for those with higher and lower values compared with those with values near the median (aHR 1.13 and 1.11, respectively). AIDS related mortality declined with increasing CD4:CD8 ratio and decreasing CD8 count.

In conclusion, the study does not lend strong support to use CD4:CD8 ratio and CD8 count as a prognostic marker for non-AIDS related mortality in virally suppressed patients on ART. However, the failure of many patients in this long-term treated HIV-infected population to reach the levels of CD4:CD8 ratio or CD8 count considered to be normal in the general population may indicate ongoing immune dysregulation. This may have longer-term consequences than the authors have been able to study here, or associations may be only with specific causes of death.