Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis.

BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.

Developing quality indicators for the care of HIV-infected pregnant women in the Dutch Caribbean.

BACKGROUND: Effective interventions to prevent mother-to-child HIV transmission (PMTCT) exist and when properly applied reduce the risk of vertical HIV transmission. As part of optimizing PMTCT in the Dutch Caribbean we developed a set of valid and applicable indicators in order to assess the quality of care in HIV-infected (pregnant) women and their newborns. METHODS: A multidisciplinary expert panel of 19 experts reviewed and prioritized recommendations extracted from locally used international PMTCT guidelines according to a 3-step-modified-Delphi procedure. Subsequently, the feasibility, sample size, inter-observer reliability, sensitivity to change and case mixed stability of the potential indicators were tested for a data set of 153 HIV-infected women, 108 pregnancies of HIV-infected women and 79 newborns of HIV-infected women in Aruba, Curaçao and St Maarten from 2000 to 2010. RESULTS: The panel selected and prioritized 13 potential indicators. Applicability could not be tested for 4 indicators regarding HIV-screening in pregnant women because of lack of data. Four indicators performed satisfactorily for Curaçao ('monitoring CD4-cell count', 'monitoring HIV-RNA levels', 'intrapartum antiretroviral therapy and infant prophylaxis if antepartum antiretroviral therapy was not received', 'scheduled caesarean delivery') and 3 for St Maarten ('monitoring CD4-cell count', 'monitoring HIV-RNA levels', 'discuss and provide combined antiretroviral therapy to all HIV-infected pregnant women') whilst none for Aruba. CONCLUSIONS: A systemic evidence-and consensus-based approach was used to develop quality indicators in 3 Dutch Caribbean settings. The varying results of the applicability testing accentuate the necessity of applicability testing even in, at first, comparable settings.

Bilateral pleural effusion in a HIV negative patient - TB or not TB?

Pleural tuberculosis is an infrequent cause of respiratory illness in Europe and usually presents unilaterally. We present the case of a young, immunocompetent sailor from the Phillippines, who presented with bilateral pleural fluid caused by Mycobacterium tuberculosis infection in the Netherlands. In addition challenges in the diagnostic process are discussed.

The efficacy of combination antiretroviral therapy in HIV type 1-infected patients treated in Curaçao compared with Antillean, Surinam, and Dutch HIV type 1-infected patients treated in The Netherlands.

We compared the efficacy of combination antiretroviral therapy (cART) of Antillean HIV-1-infected patients treated on the Caribbean island of Curaçao (CUR-AN) with Antillean (NL-AN), Surinam (NL-SUR), and Dutch (NL-NL) patients treated in The Netherlands. In total 2118 therapy-naive patients who started cART between January 2005 and August 2008 were included in the comparison. The CUR-AN patients initiated cART at a median CD4 cell count of 141 cells/mm(3) and 63% had counts below 200 cells/mm(3). Within 12 months of the start of cART 76% of the CUR-AN patients achieved viral suppression, defined as HIV-1 RNA plasma levels below 80 copies/ml. The percentage achieving viral suppression was higher in patients treated in The Netherlands (NL-AN = 87%, NL-SUR = 93%, and NL-NL = 96%). Lost to follow-up after 30 months of cART was 10% among CUR-AN patients and was higher than observed among patients treated in The Netherlands (NL-AN = 8%, NL-SUR = 3%, and NL-NL = 2%). A similar pattern was found for progression to AIDS and death (10% of CUR-AN vs. 5%, 6%, and 7% of NL-AN, NL-SUR, and NL-NL patients, respectively). Late start of cART and limited viral suppression after the start of cART determine the higher rate of disease progression to AIDS and death among Antillean patients treated in Curaçao. The high percentage of lost to follow-up may result in an underestimation of AIDS and AIDS-related death among HIV-1-infected Antilleans treated in Curaçao.