Trial data on HIV therapies in women are limited
] and discrepant results regarding the impact of gender on HAART have been reported
]. Here, we found that in a setting with free access to healthcare and HAART gender did neither affect time from eligibility to HAART, modification of therapy nor virological and immunological response to HAART.
In line with our study, European cohorts report no gender differences in time from eligibility to initiation of therapy
], while in the US a propensity to delay HAART in women compared to men is seen
]. Though, studies defined eligibility differently the estimated differences could be attributed to the reported inequality in access to HAART and healthcare in the US more than gender itself
]. In Europe, overall there is equality in access to HAART between genders, though in central and eastern Europe women tends to be favored over men
The enormous benefit of HAART is reflected by few clinical outcomes
] and therefore we assessed clinical progression by means of the virological and immunological response in patients seen after initiation of HAART. Additionally, we have earlier reported that in Denmark no major differences in terms of progression to AIDS and death are seen between men who have sex with men (MSM), heterosexually infected men and heterosexually infected women
]. Therefore we decided to focus on HIV positive patients infected heterosexually to study patients living in the same social context
We excluded intravenous drug users and HCV coinfected patients, since studies repeatedly report worse clinical outcomes
] and weaker immunological and virological responses in these patients
]. Furthermore, due to concerns about residual confounding when adjusting for IDU in the model, we chose to perform restricted analyses with exclusion of this group of patients.
Data on gender differences in CD4 count recovery after initiation of HAART are discrepant. In agreement with others
] we found no differences in CD4 recovery. On the contrary several studies report a beneficial immunological outcome in women
The lower viral load seen in women at initiation of therapy even when we excluded pregnant women is supported by several studies
] and probably has no influence on disease progression
]. Compared to other cohorts
] where HIV RNA was undetectable in 48-79% of all patients a relatively high proportion of our patients (83% of women and 92% of men) had undetectable viral load after 1 year, though, different definitions of viral suppression make studies difficult to compare.
We found no difference in virological response during follow-up between men and women, which is in accordance with earlier reports on gender differences
], however during the entire follow-up the proportion of men who had gained full viral control was greater than that of women.
Only a small part of patients were ART experienced before HAART initiation and this proportion did not differ between genders. Along with others
], we found that women were less likely to receive a HAART regimen containing efavirenz. Since the publication of teratogenicity in animal studies
] and of neural tube defects in infants exposed to efavirenz in their first trimester
] guidelines have recommended avoiding this drug in women likely to conceive. Indeed, after excluding women who initiated HAART due to pregnancy from our analysis the initial HAART regimen did not differ significantly between genders.
Regarding pharmacokinetics on HAART, data are limited, but current evidence suggests that gender differences exist
]. Reportedly, women have been found to be more likely to discontinue ART due to neurological
] and dermatologic symptoms
]. Furthermore, an increased risk of lactic acidosis
], HIV lipodystrophy
] and hepatic dysfunction
] have been reported in women. Some have speculated that the higher rate of adverse effects in women are caused by a higher drug exposure in women
Our multivariate model failed to show more treatment modifications in women of the original HAART regimen the first year after initiation compared to men. This finding is supported by others
]. Because dosing regimens of HAART are not gender specific, we adjusted for bodyweight in the analysis of IRR for treatment modifications and this did not alter results. Nor exclusion of pregnant women changed results significantly.
In contrast to our study four studies
] found that women were more likely to discontinue treatment than men. However, the first two studies have not considered pregnancy and in the latter two women were excluded when becoming pregnant. However, the UK CHIC study was able to take pregnancy into account and in this cohort women were more likely to discontinuate treatment for reasons other than virological failure
We found that women were more likely to change regimen due to gastrointestinal toxicity, though, this information needs to be interpreted with care due to small numbers.
As earlier stated some studies report that women are more likely to change regimen, because of HIV lipodystrophy
]. Since we focus on the first year after initiation of HAART only, we probably do not allow for sufficient time for this to be of clinical significance
The major strength of our study is the nationwide population-based design, linking the nationwide registers DHCS and CRS with minor loss to follow-up
and access to electronically collected longitudinal data on HIV RNA and CD4 counts.
Some limitations need to be assessed. Data on adherence and socioeconomic status are not available in our cohort and are therefore not assessed for analysis. Information on the study participants was those reported by the providers and then retrospectively summarized for this study. In the DHCS only toxicities leading to a modification are documented and therefore the risk of adverse events might be substantially higher than the incidence reported in our study. Moreover, data on virological failure is based on the discretion of the physician and might therefore not reflect the actual number of virological failures.
The route of transmission is self-reported and therefore can be misclassified. Furthermore, infection with HCV and HBV was not treated as a time-updated variable, as this information is not available in DHCS.