Jan Gerstoft

The development of therapeutic and prophylactic HIV vaccines for African countries is urgently needed, but the question of what immunogens to use needs to be answered. One approach is to include HIV envelope immunogens derived from HIV-positive individuals from a geographically concentrated epidemic with more limited viral genetic diversity for a region-based vaccine. To address if there is a basis for a regional selected antibody vaccine, we have screened two regionally separate cohorts from Guinea-Bissau and Denmark for neutralizing antibody activity and antibody-dependent cellular cytotoxicity (ADCC) against local and non-local circulating HIV-1 strains. The neutralizing activity did not demonstrate higher potential against local circulating strains according to geography and subtype determination, but the plasma from Danish individuals demonstrated significantly higher inhibitory activity than the plasma from individuals from Guinea-Bissau against both local and non-local virus strains. Interestingly, an opposite pattern was observed with ADCC activity, where Guinea-Bissau individual plasma demonstrated higher activity than Danish plasma and was specifically against the local circulating subtype. Thus, on basis of samples from these two cohorts no local-specific neutralizing activity was detected, but a local ADCC response was identified in the Guinea-Bissau samples, suggesting potential use of regional immunogens for an ADCC inducing vaccine.

Background: Information on risk of benign prostate hypertrophy (BPH) in HIV-infected men is sparse. We aimed to estimate the incidence of being diagnosed with BPH among HIV-infected men compared with an age and sex-matched comparison cohort from the background population. To exclude that family-associated risk factors influence risk of BPH diagnoses in families of HIV-infected individuals, we estimated risk of BPH in fathers of HIV-infected men and fathers of the comparison cohort. Methods: In a nationwide, population-based, matched cohort study, we calculated incidence rates and used Poisson regression models to calculate incidence rate ratios (IRRs) of being diagnosed with BPH, defined as the earliest of date of the second redeemed prescription of a drug used to treat BPH, the first registration of a BPH diagnosis in the Danish National Hospital Registry (DNHR) or the first registration of a surgical procedure for BPH in DNHR. Results: We identified 4633 HIV-infected men, 46 330 comparison cohort individuals, 1585 fathers of HIV-infected men and 20 449 fathers of the comparison cohort. Incidence rate of being diagnosed with BPH was 37.0 [95% confidence interval (95% CI) 31.5–43.1] per 10 000 person-years of follow-up among HIV-infected men and was not increased compared with the comparison cohort (IRR 1.04, 95% CI 0.88–1.22). Risk was not increased for fathers of HIV-infected men vs. fathers of the comparison cohort (IRR 0.99, 95% CI 0.87–1.12). Stratified analyses did not change the above results markedly. Conclusion: HIV-infected individuals do not have an increased risk of being diagnosed with BPH.

The mortality of HIV-infected patients in Denmark approaches that of the background population. Still, half of the HIV-infected patients are diagnosed late, resulting in poorer response to therapy, larger cost and greater transmission rate. A pan-European initiative, "HIV in Europe" has published a guideline on indicator-based HIV testing in order to improve early HIV diagnosis. The Danish Society of Infectious Diseases wishes to highlight the importance of indicator-based HIV testing, in order to improve the possibility of early diagnosis and therapy of HIV-infection.

Genetic variation upstream of the apoptosis pathway has been associated with outcome of hepatitis C virus (HCV) infection. We investigated genetic polymorphisms in the intrinsic apoptosis pathway to assess their influence on sustained virological response (SVR) to pegylated interferon-α and ribavirin (pegIFN/RBV) treatment of HCV genotypes 1 and 3 infections. We conducted a candidate gene association study in a prospective cohort of 201 chronic HCV-infected individuals undergoing treatment with pegIFN/RBV. Differences between groups were compared in logistic regression adjusted for age, HCV viral load and interleukin 28B genotypes. Four single nucleotide polymorphisms (SNPs) located in the B-cell lymphoma 2-like 1 (BCL2L1) gene were significantly associated with SVR. SVR rates were significantly higher for carriers of the beneficial rs1484994 CC genotypes. In multivariate logistic regression, the rs1484994 SNP combined CC + TC genotypes were associated with a 3.4 higher odds ratio (OR) in SVR for the HCV genotype 3 (p = 0.02). The effect estimate was similar for genotype 1, but the association did not reach statistical significance. In conclusion, anti-apoptotic SNPs in the BCL2L1 gene were predictive of SVR to pegIFN/RBV treatment in HCV genotypes 1 and 3 infected individuals. These SNPs may be used in prediction of SVR, but further studies are needed.

Treponema pallidum, the causative agent of syphilis, elicits a vigorous immune response in the infected host. This study sought to describe the impact of syphilis infection on hepatitis C virus (HCV) RNA levels in patients with HIV and chronic HCV infection. Patients with chronic HIV/HCV and syphilis co-infection were identified by their treating physicians from 1 October 2010 to 31 December 2013. Stored plasma samples obtained before, during, and after syphilis infection were analysed for interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and IFN-γ-inducible protein 10 kDa (IP-10). Undetectable HCV RNA at the time of early latent syphilis infection was observed in 2 patients with HIV and chronic HCV infection. After treatment of the syphilis infection, HCV RNA levels increased again in patient 1, whereas patient 2 initiated HCV therapy and remained HCV RNA-negative. Available plasma samples obtained before and after the episode with undetectable HCV RNA were phylogenetically identical, making the possibility of spontaneous clearance and HCV reinfection less likely. The IL-10, TNF-α, and IP-10 levels increased at the time of syphilis diagnosis in patient 1 and decreased again after treatment of the syphilis infection. We propose that T. pallidum-induced cytokine secretion resulted in an immune response hindering HCV replication during syphilis infection. We suggest that HIV/HCV-co-infected patients with unexpected undetectable HCV RNA are tested for syphilis infection and that the serological tests include both non-treponemal and treponemal tests to avoid false-positive results caused by HCV.

By the end of 2009 an estimated 2.5 million children worldwide were living with HIV-1, mostly as a consequence of vertical transmission, and more than 90% of these children live in sub-Saharan Africa. In 2008 the World Health Organization (WHO), recommended early initiation of Highly Active Antiretroviral Therapy (HAART) to all HIV infected infants diagnosed within the first year of life, and since 2010, within the first two years of life, irrespective of CD4 count or WHO clinical stage. The study aims were to describe implementation of EID programs in three Tanzanian regions with differences in HIV prevalences and logistical set-up with regard to HIV DNA testing.

Soluble CD163 (sCD163) has been associated with arterial inflammation and non-calcified plaques in human immunodeficiency virus (HIV)-infected individuals and has therefore been suggested as a predictive biomarker of myocardial infarction (MI). We conducted a nested case–control study of 55 cases with first-time MI and 182 controls matched for age, duration of antiretroviral therapy (ART), gender, smoking, and no known cardiovascular disease. All patients had four available plasma samples, 1: Before initiation of antiretroviral therapy (ART), 2: Three months after ART, 3: One year before the case’s MI, and 4: The last sample available before the case’s MI. We used conditional logistic regression to estimate the association of sCD163 with first-time MI. The two groups had similar HIV-parameters and cardiovascular risk factors were equally distributed. There was no significant association between sCD163 and MI neither in samples obtained one year before (OR 1.05, CI 95% 0.85 – 1.29, p = 0.66) nor two months before (OR 1.20, CI 95% 0.98-1.47 p = 0.08). sCD163 did not prove to be a useful biomarker for prediction of first-time MI in a HIV-infected population.

HIV patients are known to be at increased risk of lung cancer but the risk factors behind this are unclear.