The aging population observed in the present analysis, across all gender/sexual orientation groups, was likely primarily a result of the success of cART and
198 lower rates of death over calendar time in Section 5.4.1.5 ). Moreover, there have been increases in diagnosis of HIV among older individuals over time567. In terms of the decreasing proportion of individuals of white ethnicity over time in the present study, this was primarily owing to the observed increase in prevalence of unknown ethnicity status. It was unlikely a result of an increase in individuals of non-white ethnicity, since in recent years the prevalence of new diagnoses among migrants and black-African individuals has been falling in Europe543;568.
There was little difference between the gender/sexual orientation groups in terms of specific NRTI backbones and ARV classes used. This suggests that differences in ART regimen are unlikely to explain gender/sexual orientation differences observed in virological non-suppression. There was lower PI-use (boosted or un-boosted) among women between 2000 and 2004, but usage of this class was similar between
gender/sexual orientation groups after this time.
Across the study population, 70% MSM, 52% MSW and 66% women had a CD4 count above the lower limit of the normal range (i.e. above 500 cells/µL) by 2014, indicating that the majority of individuals in all three groups were generally in good overall health with respect to their immunological status by this time. Although the majority of
individuals had a CD4 count that would be considered to be in the ‘normal range’, there are data which show that a higher CD4 count is associated with lower risk of AIDS and death even among individuals with a CD4 count >500 cells/µL569. Since CD4 count was analysed among all individual attending the ICDC, regardless of time since HIV diagnosis or whether they had been ART-treated, the lower CD4 counts in the heterosexual groups could reflect later HIV diagnosis, delays in ART initiation, or poorer CD4 count reconstitution following ART initiation.
Improvements in virological suppression from 2000 to 2014 at the entire clinic population level were likely reflective primarily of the corresponding increases in prevalence of ART use (Section 5.4.1.2 ). Additionally there were substantial changes in the NRTI regimen backbones used over time away from AZT, ddI and d4T towards FTC and TDF476. Use of more efficacious ARVs and ones that can be taken in a single combined tablet may also have contributed to the improvements in virological status over time.
Hospitalisation and AIDS rates were higher among MSW and women compared to MSM. When individuals hospitalised or with AIDS events at presentation were
excluded, respectively, the differences in rates between the gender/sexual orientation groups were substantially attenuated. This indicates that the still high prevalence of
199 late presentation may be a key driver for the differences in clinical outcomes by
gender/sexual orientation. It is also possible that these differences in late presentation affect the virological trends, however, pre-cART CD4 count is not usually an important factor when considering virological response to cART462, and it is likely that this has been adjusted for to some extent by adjusting for new patient status.
In analyses of individuals currently receiving continuous cART, there was a non-linear association between calendar year and virological non-suppression. Before 2006, there were declines in the prevalence of virological non-suppression over time in all three gender/sexual orientation groups. However, since approximately 2006 there was no evidence of an improvement in virological non-suppression in any gender/sexual orientation groups. It is important to consider whether this means that levels of non- suppression seen in 2006-14 represent a “best case scenario” beyond which improvements are not possible. However, although differences were quite small in absolute terms, the higher prevalence of virological non-suppression for MSW and women even in the post-2006 period would suggest that improvements in these two groups should be possible to achieve the levels seen in MSM. Potential reasons for virological non-suppression in the era of highly effective cART should be considered. Non-adherence to ART is the most likely reason for virological non-suppression on treatment. Although many individuals maintain high levels of adherence to treatment and achieve sustained virological suppression, cART is a life-long treatment, and short periods of low- or non-adherence and associated viral breakthroughs are likely to occur for some individuals570. Even in recent years, a substantial proportion of
individuals were diagnosed with HIV with a low CD4 count210;543 (thus starting cART at a more advanced HIV stage96), which may complicate treatment, compromise
virological response and result in higher levels of virological non-suppression than may be optimally achieved.
Among individuals who ever started cART, from 2006 onward there was some
evidence of a decreasing prevalence of virological non-suppression among MSM and women, although not among MSW. The fact that there were declines under this analysis strategy, but not using the first analysis strategy over the same period, indicates that these improvements may be a result of fewer treatment
disruptions/discontinuations over time571-573, which were excluded in the “currently receiving cART” analysis. There was some evidence that the difference in prevalence of virological non-suppression between MSW and both MSM and women increased between 2006 and 2014, thus perhaps treatment disruptions had not declined as much among MSW. There may also be some barriers to virological suppression that affect MSW to a greater extent than MSM or women. These may include barriers to
200 engagement with medical care, such as experiences of stigma574;575, factors that could impact on adherence to ART, and factors that may potentially impact on virological outcomes independently of adherence, such as late diagnosis210;576.
In addition to differences in virological outcome between MSM and the heterosexual groups, women had a 26% lower adjusted PR of VL >50 copies/mL than MSW among individuals currently receiving cART. However, this was only found in the main
analysis in this particular sub-population. Due to the inconsistency of this result under different analysis strategies, it should be interpreted with caution.
Methodologically, this chapter draws attention to the impact of choice of denominator on the estimated prevalence of virological non-suppression. In the “currently receiving continuous cART” analysis, individuals who had interrupted treatment at the time of their VL measurement or at any time during the previous six months were excluded. Thus, this provides a “best case scenario”. On the other hand, the analysis of individuals who ever started cART may be overly pessimistic, since individuals who completely discontinue cART are included in the denominator. The prevalence of women initiating cART in pregnancy was not accounted for in this chapter. Therefore, although it is not recommended and in recent years has become less frequent, discontinuations of treatment after pregnancy may account for some of the greater prevalence of virological non-suppression among women who have ever been on cART577;578. There are some circumstances, even since the results of the START study in 2006162, in which an individual may need to temporarily stop treatment. Reasons may include serious side effects or drug toxicities, development of other illnesses where concurrent treatment is not possible (drug interactions), and to participate in a clinical trial. Therefore, there are advantages and disadvantages to both
denominators. In the current era, non-adherence to treatment and short-term interruptions are the main predictors of poorer virological response199, and as such, they are likely mediators for associations between gender/sexual orientation and VL non-suppression among cART-treated individuals. Thus the “ever on cART” analysis, which allows for the variability in virological response according to differences in treatment disruptions, may be the most relevant analysis in this context. However, completely discontinuing treatment is different to incomplete adherence with respect to resistance development172, thus with respect to separating these adherence patterns, the analysis of individuals currently receiving cART offers useful information.