Smoking is strongly and consistently
Smoking is strongly and consistently associated with periodontitis in the general population. In our study we detected a similar pattern in patients with HIV infection: smokers had a higher DPSI score compared to non-smokers. The exact cause of smoking as a risk factor for periodontitis in the general population is still unclear. Smoke components may impair the innate apexbio dilution against pathogens, alter antigen presentation and modulate the adaptive immune response.44, 45 In other studies periodontitis was also more prevalent in smoking compared to non-smoking HIV-infected patients.16, 19
The major strength of our study is the complete and refined data collection for all patients, i.e., thorough medical history recording and detailed documentation of oral health characteristics, as well as comprehensive registration of immunological and virologic values. Additionally, the broad inclusion of patients may allow the generalization of our findings in similar Western European populations. Limitations, however, also apply. In the group of HIV infected patients, DPSI was applied to score presence of severe periodontitis (DPSI ≥ 3 + ), while in controls presence of severe periodontitis was based on presence of pocket depths ≥ 6 mm after full mouth periodontal probing. Since DPSI ≥ 3 + corresponds to presence of pocket depths ≥ 6 mm, we considered that the applied cut-off values (DPSI ≥ 3 + and pocket depth ≥ 6 mm) for presence of severe periodontitis are comparable. In our group of HIV infected patients 85% is male, which is in agreement with the gender distribution of HIV infected patients in Groningen and the Netherlands (81% male, Table 3). Furthermore, we applied questionnaires to assess the presence of general health issues instead of specific blood tests for underlying diseases as, e.g., diabetes mellitus. Consequently, patients might not have reported a disease, either because they did not mention it or were not aware of it yet, which may have resulted in underestimation of prevalence of health issues in our patient and control cohort. Additionally, we did not specify the type of cardiovascular diseases, but we only registered their presence. However, the use of questionnaires to assess general health is a rather common approach.
Introduction Combined antiretroviral therapy (cART) has constituted major progress in the treatment of HIV infection and current recommendations are to treat all HIV-infected persons, regardless of the stage of infection. Although cART can efficiently block HIV replication, it cannot completely eliminate the virus from its reservoirs. In particular, infected resting CD4+ T-cells containing latent integrated HIV proviruses are refractory to current cART and represent a major hurdle preventing viral eradication [1,2]. Understanding the pathogenesis of HIV reservoirs is critical for developing and evaluating new therapeutic strategies aimed at viral eradication or functional cure. Integrated HIV DNA is the most stable and functional form of the viral genome. It plays a major role in the pathogenesis of HIV infection and HIV reservoirs, even if it includes both replication-competent and defective genomes [, , ]. Cells containing integrated HIV DNA can produce new infectious virions upon stimulation and activation [6,7]. Proviruses persist indefinitely, partly due to the homeostatic proliferation of memory T-cells. In contrast, unintegrated forms, which include linear and episomal HIV DNA with 1- or 2-LTRs, are considered more labile and are surrogate markers of viral replication [8,9]. Total HIV DNA levels in peripheral blood mononuclear cells (PBMCs) have been described during both the natural history of HIV infection and cART . It remains partially unexplained why the decrease in this surrogate marker of the reservoir is greater and faster when treatment is initiated during primary HIV infection (PHI) than during the chronic stage [, , ]. As for integrated HIV DNA, it has been mostly studied in patients on cART [, , ]. Only a few studies have measured integrated HIV DNA in untreated patients, most of which include fewer than 20 patients [14,, , ]. Longitudinal data are even more scarce for both markers: only one study to our knowledge has a follow-up of patients during untreated infection (17 patients during the first year, among which 10 still followed after 2.8 years) . Moreover, some techniques do not allow a comparison between the amounts of total and integrated HIV DNA because of differences in assay standardization  and the long-term dynamics of integrated forms among total HIV DNA have never been described. Besides, all previous results showed a great inter-individual variability of total and integrated HIV DNA [14,16,17,20,21], enhancing the need for studies on large cohorts.