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Survey of the temporal changes in HIV-1 replicative fitness in the Amsterdam cohort
No full textChanges in virulence and fitness during an epidemic are common among pathogens. Several studies have shown that HIV fitness increases within a patient during disease progression, while bottlenecks, such as sexual transmission, immune pressure and drug treatment can reduce fitness. In this study, we analyzed how these opposing forces have shaped HIV-1 fitness over time. Therefore, we compared the replicative fitness of HIV-1 isolates from newly infected untreated individuals, diagnosed for HIV-1 infection early in the AIDS epidemic in Amsterdam, the Netherlands, with more recent isolates. Twenty-five early and late HIV-1 isolates, carefully matched for seroconversion time, were competed head-to-head in a dual infection/competition assay, employing peripheral blood mononuclear cells. In contrast with previous studies, we observed a trend of increasing fitness over time in the HIV epidemic of Amsterdam. Apparently, the bottleneck, occurring with each transmission event, does not completely reset the fitness increase acquired during disease progression
The intraspleen huPBL NOD/SCID model to study the human HIV-specific antibody response selected in the course of natural infection
No full textThe intrasplenic injection of human peripheral blood mononuclear cells (PBMCs) into severely immune deficient NOD/SCID mice, causes a massive and transient dominant expansion of human B cells in the spleen. This permits the easy isolation of human monoclonal antibodies specific for different antigens by a Kohler and Milstein-based method. Here we studied the human HIV-specific antibody response in the circulation of mice after intrasplenic transfer of PBMC from untreated HIV-infected patients with detectable to high viral load as well as from HAART-treated and from untreated patients, who kept an undetectable viral load (the latter referred to as "natural suppressors"). Excellent B cell expansion was obtained for all PBMC. High level replication of virus was observed after transfer of PBMC of untreated viremic patients only. A strong and multispecific HIV-specific antibody response was observed after transfer of PBMC of untreated viremic patients and natural suppressors. In contrast, only a weak and pauci-specific antibody response was detected in mice reconstituted with PBMC from successfully treated patients. Based on these observations we conclude that the use of the intraspleen mouse model confirmed a) the presence of HIV-specific circulating memory B cells in untreated patients and natural suppressors; b) the nearly complete absence of circulating memory B cells in patients receiving highly active antiretroviral therapy. Using the intraspleen model we generated large numbers of immortalized B cells and isolated two anti-p24 human monoclonal antibodies. We further conclude that the intraspleen huPBL NOD/SCID model is a small animal model useful for the analysis of the antibody response against HIV found in patients
HIV and other sexually transmitted infections among female sex workers in Kinshasa, Democratic Republic of Congo, in 2002
No full textOBJECTIVE: The objective of this study was to determine the prevalence and risk factors of HIV and other sexually transmitted infections (STIs) among female sex workers (FSWs) in Kinshasa, Democratic Republic of the Congo, in 2002. STUDY DESIGN: A cross-sectional study was conducted among FSWs presenting for the first time at the STI clinic of Matonge, Kinshasa. The women were interviewed about sociodemographic characteristics, type of sex work, and sexual behavior. Blood was taken for HIV, syphilis, and herpes simplex virus type 2 serology. Vaginal secretions were collected on swabs for the diagnosis of gonorrhea, chlamydia, and trichomoniasis. RESULTS: The overall HIV prevalence was 12.4% but varied within the different categories of FSWs: 11.8% in hotel-based, 24.0% in home-based, and 20.0% in street-based FSWs; 10.0% in homeless FSWs; and 6.6% in Masquées (clandestine sex workers). The overall herpes simplex virus type 2 seroprevalence was 58.5%. CONCLUSIONS: The prevalence of HIV and other STIs seems to have stabilized since the beginning of the project in 1988
Genetic variation in Rhipicephalus appendiculatus Acari: Ixodidae from Zambia: correlating genetic and ecological variation with Rhipicephalus appendiculatus from eastern and southern Africa
No full textBased on their ecology, Rhipicephalus appendiculatus ticks from eastern and southern Africa have been divided into three groups. We investigated how two geographic genetically differentiated stocks of R. appendiculatus from the southern and the eastern provinces of Zambia, representing two ecological groups, i.e., southern African and transition groups, respectively, genetically compare to stocks from east Africa (Rwanda) and southern Africa (Zimbabwe and South Africa). The ITS2 and two mitochondrial genes segments, 12s rDNA and COI, were used in the investigations. The ITS2 tree did not show support for differentiation into any groups, while the two mitochondrial genes trees (12s rDNA and COI) showed two genetically differentiated groups: an east African genetic group which included specimens from Rwanda and the plateau area of the eastern province of Zambia, and a southern African genetic group represented by specimens from South Africa, Zimbabwe and specimens collected on the fringes of the eastern province plateau in the Nyimba district of Zambia. This suggests that the two geographically differentiated stocks of the southern and eastern provinces of Zambia might be part of two wider geographic genetically differentiated R. appendiculatus groups that extend beyond Zambia. Stocks of "transition" ecology (eastern province) belong to the east African genetic group and the differences in ecology within this genetic grouping may be due to genetic polymorphism, phenotypic plasticity, and other local factors
In vitro pre- and post-exposure prophylaxis using HIV inhibitors as microbicides against cell-free or cell-associated HIV-1 infection
No full textSeveral classes of microbicides are being evaluated for the prevention of sexual HIV transmission. In vivo, the infectious dose and viral source involved in transmission remain uncertain and it is likely that women will use microbicides both before and after high-risk HIV exposure. Therefore, we evaluated HIV entry inhibitors (EIs) and reverse transcriptase inhibitors (RTIs) for their ability to block cell-free and cell-associated HIV-1 infection in co-cultures of monocyte-derived dendritic cells (MO-DC) and CD4+ T-cells using settings of pre- and post-exposure prophylaxis. In the pre-exposure assay, where compound was present before, during and 24 h after infection, all tested EIs (BMS806, TAK779 and T20) and RTIs (PMPA, TMC120 and UC781) blocked infection with 10(-4) multiplicity of infection (MOI) of cell-free virus at a dose between 100 and 10,000 nM, dependent on the compound used. At 10(-3) MOI, however, only T20 and the RTIs completely blocked infection. Furthermore, in experiments with cell-associated virus, EIs were ineffective, whereas RTIs actively blocked infection with similar potency as in the experiments with cell-free virus. In the post-exposure assay, where compound was added 2 h after infection and remained present for 24 h, EIs were inactive whereas RTIs blocked cell-free and cell-associated viral infections equally efficiently. Moreover, post-exposure prophylaxis initiated 24 h after infection with cell-free or cell-associated HIV-1 was still effective with 1,000 nM of TMC120. Both EIs and RTIs were non-cytotoxic at any tested concentration for MO-DC and CD4+ T-cells in co-culture. Our study shows that RTIs are potent inhibitors of cell-free and cell-associated virus used either in pre- or post-exposure settings. It highlights that parameters such as viral input, viral source, the time of compound addition and the target cells should be considered in microbicides evaluation
Results of a Europe-wide investigation to assess the presence of a new variant of Chlamydia trachomatis
No full textSexual dysfunction in HIV-positive men is multi-factorial: a study of prevalence and associated factors
No full textThis is an electronic version of an article published in AIDS Care. 2007 Sep;19(8):955-65. AIDS Care is available online at informaworldTMTo establish the prevalence of sexual dysfunction amongst HIV-positive men and to determine the factors associated with dysfunction we conducted a cross-sectional study in seven European HIV treatment centres. Data on medical history, antiretroviral treatment and laboratory results were collected by interview and case record review. Sexual function was evaluated by the participant self-completion of a questionnaire based on the International Index of Erectile Function (IIEF) 711/929. Seventy-seven percent of participants returned the questionnaire. Data from 668 (72%) respondents were included. Thirty-three percent (95%CI: 29.4-36.5%) had moderate/severe erectile dysfunction (EDF) and 24% (95%CI: 20.9-27.3%) had moderate to severe impairment of sexual desire. Variables significantly associated with EDF in multivariable analysis were older age (greater than 40 years), heterosexual status, non-alcohol drinking status, depression, antidepressants, psychotropic medications and duration of ARV therapy. Low sexual desire (LSD) was associated with older age (greater than 40 years), depression and black African ethnicity. We establish that EDF and LSD are common in both ARV naïve and ARV experienced, HIV-positive individuals. Erectile dysfunction was associated with long duration of ARV treatment, with a significantly increased risk of dysfunction in the quartile with the longest period of exposure. No significant association was seen with specific classes of anti-retrovirals. Older age, and depression were the variables most consistently associated with both EDF and LSD
Dengue fever and pregnancy; a review and comment
No full textBACKGROUND: The increasing incidence of dengue with the concomitant rise in travel during pregnancy makes it likely that a pregnant woman will plan travel to or present after travel to endemic areas. METHOD: Literature search and communication with researchers. RESULTS: Case reports of dengue during pregnancy, the peripartum period and neonatal dengue were found. There is little systematic research. CONCLUSIONS: Pregnancy appears not to increase the incidence or severity of dengue, but some case reports suggest that dengue may predispose to certain pregnancy complications. Transplacental infection occurs, but protective antibodies pass transplacentally and fetal effects may be minimal given sufficient immune response. In near-term disease, severe fetal or neonatal illness and death may occur. Such illness may also predispose the newborn to subsequent dengue hemorrhagic fever. Clinicians should be aware that presentation in either maternal or neonatal disease may be atypical and confound diagnosis. Women in late pregnancy should avoid travel to areas of ongoing disease, and those earlier in pregnancy should consider dengue a serious hazard. If travel is unavoidable, mosquito avoidance measures are mandated. If a woman acquires dengue fever while pregnant, conservative medical and obstetrical management are the treatments of choice. Further research is required