Prevalence of viral sexually transmitted infections and HPV high-risk genotypes in women in rural communities in the Department of La Paz, Bolivia.

BACKGROUND: Bolivia has the highest prevalence of cervical cancer in South America and the prevalence of viral sexually transmitted infections (STIs) among people in urban cities is increasing. Little is known about the prevalence of viral STIs in rural communities, which generally have limited access to health care. In order to study the prevalence of viral STIs in rural Bolivia, we recruited women from villages and towns in the Department of La Paz in Bolivia. METHODS: Three hundred ninety-four female participants were assessed for IgG-antibodies to herpes simplex virus type 2 (HSV-2), human immunodeficiency virus (HIV) and hepatitis B virus (HBV, anti-HBc), as well as for the presence of HBV surface antigen (HBsAg) in dried blood spots. The prevalence of 12 high-risk types of human papillomavirus (HPV) was assessed by qPCR in dried cervicovaginal cell spots from 376 of these women. χ2 test was used to compare variables between the populations and binary logistic regression was used to identify risk factors associated with the positivity of the tests. RESULTS: The seroprevalence of HSV-2 was 53% and of HBV 10.3%. HBAg was detected in 15.8% of women with anti-HBV antibodies indicating chronic infection. The frequency of high-risk HPV infection was 27%, with the most prevalent high-risk HPV types being HPV 56, 39 and 31 followed by HPV 16 and 18. Finally, none of the 394 women were seropositive for HIV, and about 64% of the studied population was positive for at least one of the viral infections. CONCLUSIONS: Women in Bolivian rural communities in La Paz show a high prevalence of HBV, HPV and, in particular, HSV-2. In contrast, none of the women were HIV positive, suggesting that the HIV prevalence in this population is low. The pattern of high-risk HPV types differed from many other countries with a predominance of HPV-types not included in the Gardasil vaccine which was officially introduced in Bolivia in April 2017.

Human immunodeficiency virus type 1 resistance or cross-resistance to nonnucleoside reverse transcriptase inhibitors currently under development as microbicides.

Microbicides based on nonnucleoside reverse transcriptase inhibitors (NNRTIs) are currently being developed to protect women from HIV acquisition through sexual contact. However, the large-scale introduction of these products raises two major concerns. First, when these microbicides are used by undiagnosed HIV-positive women, they could potentially select for viral resistance, which may compromise subsequent therapeutic options. Second, NNRTI-based microbicides that are inactive against NNRTI-resistant strains might promote the selective transmission of these viruses. In order to address these concerns, drug resistance was selected in vitro by the serial passage of three viral isolates from subtypes B and C and CRF02_AG (a circulating recombinant form) in activated peripheral blood mononuclear cells (PBMCs) under conditions of increasing concentrations of three NNRTIs (i.e., TMC120, UC781, and MIV-160) that are currently being developed as candidate microbicides. TMC120 and MIV-160 displayed a high genetic barrier to resistance development, whereas resistance to UC781 emerged rapidly, similarly to efavirenz and nevirapine. Phenotypically, the selected viruses appeared to be highly cross-resistant to current first-line therapeutic NNRTIs (i.e., delavirdine, nevirapine, and efavirenz), although they retained some susceptibility to the more recently developed NNRTIs lersivirine and etravirine. The ability of UC781, TMC120, and MIV-160 to inhibit the in vitro-selected NNRTI-resistant viruses was also limited, although residual activity could be observed for the candidate microbicide NNRTI MIV-170. Interestingly, only four p2/p7/p1/p6/PR/RT/INT recombinant NNRTI-resistant viruses (i.e., TMC120-resistant VI829, EFV-resistant VI829, MIV-160-resistant VI829, and EFV-resistant MP568) showed impairments in replicative fitness. Overall, these in vitro analyses demonstrate that due to potential cross-resistance, the large-scale introduction of single-NNRTI-based microbicides should be considered with caution.

Human immunodeficiency virus type 1 (HIV-1) integration: a potential target for microbicides to prevent cell-free or cell-associated HIV-1 infection.

Conceptually, blocking human immunodeficiency virus type 1 (HIV-1) integration is the last possibility for preventing irreversible cellular infection. Using cocultures of monocyte-derived dendritic cells and CD4(+) T cells, which represent primary targets in sexual transmission, we demonstrated that blocking integration with integrase strand transfer inhibitors (InSTIs), particularly L-870812, could consistently block cell-free and cell-associated HIV-1 infection. In a pretreatment setting in which the compound was present before and during infection and was afterwards gradually diluted during the culture period, the naphthyridine carboxamide L-870812 blocked infection with the cell-free and cell-associated HIV-1 Ba-L strain at concentrations of, respectively, 1,000 and 10,000 nM. The potency of L-870812 was similar to that of the nucleotide reverse transcriptase inhibitor R-9-(2-phosphonylmethoxypropyl) adenine (PMPA) but one or two orders of magnitude lower than those of the nonnucleoside reverse transcriptase inhibitors UC781 and TMC120. In contrast, the diketo acid RDS derivative InSTIs showed clear-cut but weaker antiviral activity than L-870812. Moreover, L-870812 completely blocked subtype C and CRFO2_AG primary isolates, which are prevalent in the African heterosexual epidemic. Furthermore, the addition of micromolar concentrations of L-870812 even 24 h after infection could still block both cell-free and cell-associated Ba-L, opening the prospect of postexposure prophylaxis. Finally, an evaluation of the combined activity of L-870812 with either T20, zidovudine, PMPA, UC781, or TMC120 against replication-deficient HIV-1 Ba-L (env) pseudovirus suggested synergistic activity for all combinations. Importantly, compounds selected for the study by using the coculture model were devoid of acute or delayed cytotoxic effects at HIV-blocking concentrations. Therefore, these findings provide evidence supporting consideration of HIV-1 integration as a target for microbicide development.

In vitro pre- and post-exposure prophylaxis using HIV inhibitors as microbicides against cell-free or cell-associated HIV-1 infection.

Several 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.

Evaluacion de la Toxicidad delextracto de Surucuina, un nuevo inhibidor de la Fosfolipasa a2, en Sistemas de Cultivo Celular / Evaluation of the Toxicity of the extract of Surucuina, a new inhibitor of fosfolipasa a2, is Systems of Cellular Culture

En la búsqueda de nuevas alternativas terapéuticas, nos encontramos con diversos productos naturales que son ortginarios de nuestro país. La surucuina, entre estos, ha mostrado cualidades promisorias para el tratamiento de patologías relacionadas con la actividad de lafosfolipasa A2. Sin embargo, para planificar su uso corno producta terapéutico, es neesario contar con estudios de seguridad preclínica. En este trabajo se evaluó la toxicidad de la surucaina en sistemas de cultivo celular primaria (esplenocitos murinos) y continuo (células de riñón de hamster BHK-21 y células de carcinoma cervival humana HeLa). La actividad citotóxíca inducida por d!ferentes concentraciones del producto, en cultivos de 120 a 1 8 horas, fué determinada por el método de exclusión de un colorante vital y el ensayo del M7T. Los resultados evidenciaron ausencia de efectos citotóxicos en todos los sistemas celulares. No se detectaron efectos citopáticos ni citolíticos aún en cultivos prolongados; por el contrario, se evidenció una actividad estimuladora o protectora celular de este ethnoproducto nacional

Inmunidad Antiviral contra el virus dela Rubeola: Estudio piloto seroepidemiologico en mujeres en edad reproductiva / Antiviral immunity against the virus of the Rubeola: Study seroepidemiologico pilot in women in reproductive age

La infección por el virus de la rubeola contraída por mujeres en estado de gravidez puede causar en el feto un cuadro clínico que incluye malformaciones congénitas de diverso grado de severidad. La incidencia de infección congénita puede llegar hasta un 90 porciento durante los primeros meses de concepción, por lo que la reactividad inmunitaria juega un rol vital. La importancia de esta infección en nuestra población aún no se ha establecido, en este trabajo se determinó la inmunidad anti-rubeola de 92 mujeres voluntarias de 15 a 38 años de edad mediante la cuantificación de anticuerpos antivirales tipo IgG por ensayo inmunoenzimático. De la población estudiada, 13 porciento es susceptible a contraer la infección y el 18.5 porciento presenta baja concentración de anticuerposilO a 50 UI/mi). Estos resultados sugieren que el control de ia inmunidad antirubeola debería inciuirse en la asistencia prenatal y que la vacuna debería también dirigirse a población femenina, previa determinación de susceptibilidad inmunitaria