Interruption of combination antiretroviral therapy in HIV-1-infected individuals leads to rapid viral rebound. Here we report the results of a phase IIa open label clinical trial evaluating 3BNC117,a ...broad and potent neutralizing antibody against the CD4 binding site of the HIV-1 Env protein, during analytical treatment interruption in 13 HIV-1-infected individuals. Participants with 3BNC117-sensitive virus outgrowth cultures were enrolled. Results show that two or four 30 mg kg(-1) 3BNC117 infusions,separated by 3 or 2 weeks, respectively, are generally well tolerated.Infusions are associated with a delay in viral rebound of 5-9 weeks after two infusions, and up to 19 weeks after four infusions, or an average of 6.7 and 9.9 weeks, respectively, compared with 2.6 weeks for historical controls (P < 0.00001). Rebound viruses arise predominantly from a single provirus. In most individuals,emerging viruses show increased resistance, indicating escape.However, 30% of participants remained suppressed until antibody concentrations waned below 20 μg ml(-1), and the viruses emerging in all but one of these individuals showed no apparent resistance to 3BCN117, suggesting failure to escape over a period of 9-19 weeks.We conclude that the administration of 3BNC117 exerts strong selective pressure on HIV-1 emerging from latent reservoirs during analytical treatment interruption in humans.
The present cross-sectional study evaluated the status and relationship of interleukin-6, a platelet growth factor, with platelet counts, viral load, CD4 counts, and antiretroviral treatment in 75 ...HIV-infected subjects with thrombocytopenia and 50 gender-, race-, age- and antiretroviral treatment-matched controls without thrombocytopenia. Mean IL-6 production was significantly higher in thrombocytopenic participants (13 432 ± 8596) than in non-thrombocytopenic subjects (12 859 ± 3538 pg 105 Lym). Univariate analyses indicated, however, that thrombocytopenic patients were more likely to have <3000 pg of IL-6 than non-thrombocytopenic patients (OR = 7 95% CI 1.3-12; P = 0.01). For additional analyses, participants were dichotomized above and below 3000 pg of IL-6. Despite similar age, gender, drug use and antiretroviral treatment, thrombocytopenic participants had lower CD4 counts (186.5 ± 149 vs. 401 ± 286, P = 0.005) than non-thrombocytopenic subjects. Thrombocytopenic participants with elevated IL-6, with or without HAART, were more likely to have higher HIV-replication (496 273 ± 210 416; 34 656 ± 25 332) than thrombocytopenic individuals with low IL-6 levels (105 332 ± 42 699; 19 015 ± 14 296 P = 0.05). Non-thrombocytopenic patients with high IL-6 levels exhibited the highest CD4s (466.7 ± 333) and the lowest viral burden (63 094 ± 53 300) of the groups. Two distinct categories of HIV-associated thrombocytopenia exist: one accompanied by low IL-6, and another with compensatory elevations of IL-6. In thrombocytopenic individuals, the latter was associated with the poorest immunological and virological responses.
As HIV infection is increasing among women, evaluation, prevention, and education campaigns need to target this vulnerable population. Because of their frequent and accepted contact with members of ...the community, female law officers, if knowledgeable, could be well suited to provide information/education related to HIV/STD transmission. A survey of HIV/AIDS knowledge and risk behaviors was administered to 120 law enforcement women (LEW) and 60 women from the general population (GPW) in Bogotá, Colombia. LEW indicated a very high (90%) understanding of basic HIV knowledge. Although most (52%) of the LEW did not report high-risk behaviors, 29% indicated having unprotected sex during menses, and 17% had unprotected anal sex. This contrasts, however, with GPW, who were of similar age, but had a significantly higher prevalence (73%) of risky behaviors (P=.004). Moreover, 52% of the GPW reported having unprotected anal sex, and approximately half of this group (55%) indicated having unprotected sex during menses. Alcohol and drug users were also more prevalent in the GPW: 14% frequently used alcohol and 3% inhaled drugs during sexual encounters, contrasted to 2% of LEW reporting alcohol use. GPW were four times more likely than LEW, to engage in high-risk sexual practices 95% confidence interval (CI)=1.9-10.4, P=0.034. Multivariate analyses indicated that alcohol and/or drug use were significantly associated with high-risk sexual practices odds ratio (OR)=4.7, 95% confidence intervals (CI)=1.3-18.4, P=.02). Improved educational HIV/AIDS programs are needed, particularly for women in the general population, who use alcohol/drugs during sexual encounters, which account, at least in part, for their high-risk behaviors. Women in law enforcement, who appear knowledgeable and exhibit safer behaviors, could be useful educators for GPW. Because of their professional role in the community, training for LEW in HIV/AIDS education/prevention programs should be considered.
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