World Journal of AIDS最新文献

Antiviral drugs currently on the market primarily target proteins encoded by specific viruses. The drawback of these drugs is that they lack antiviral mechanisms that account for resistance or viral mutation. Thus, there is a pressing need for researchers to explore and investigate new therapeutic agents with other antiviral strategies. Viruses such as the human immunodeficiency virus (HIV) alter canonical signaling pathways to create a favorable biochemical environment for infectivity. We used Qiagen Ingenuity Pathway Analysis (IPA) software to review the function of several cellular kinases and the resulting perturbed signaling pathways during HIV infection such as NF-κB signaling. These host cellular kinases such as ADK, PKR, MAP3K11 are involved during HIV infection at various stages of the life cycle. Additionally IPA analysis indicated that these modified host cellular kinases are known to have interactions with each other especially AKT1, a serine/threonine kinase involved in multiple pathways. We present a list of cellular host kinases and other proteins that interact with these kinases. This approach to understanding the relationship between HIV infection and kinase activity may introduce new drug targets to arrest HIV infectivity.

Background: In 2003 a large-scale HIV prevention program was launched for key populations in six high HIV prevalence states of India. This paper assesses the effect of exposure to the intervention on condom use with commercial clients and experiences of sexually transmitted infection (STI) among female sex workers (FSWs) in Tamilnadu, a southern Indian state, between 2006 and 2009.

Methods: Data were drawn from two rounds of cross-sectional surveys conducted in 2006 (N = 2010) and 2009 (N = 2500) among FSWs in Tamilnadu, recruited through probability-based sampling. A series of multivariate logistic regression models were constructed to examine the association between exposure to the intervention and change over time with condom use and self-reported STI. All the analyses were performed using STATA 11.1.

Results: Overall, 48% of FSWs in 2006 and 90% in 2009 reported exposure to the intervention. Compared to 2006, there was a considerable increase in the proportion of FSWs reporting consistent condom use with regular and occasional clients at follow-up (2009). Further, the increase in consistent condom use over time with occasional (adjusted OR = 3.53, 95% CI: 2.47 - 5.05) and regular clients (adjusted OR = 4.97, 95% CI: 3.43 - 7.16) was significantly higher among FSWs exposed to the intervention than those not exposed. Additionally, a significant decline was observed in self-reported STI overtime among FSWs exposed to the intervention compared to their counterparts (adjusted OR = 0.39, 95% CI: 0.26 - 0.59).

Conclusion: The HIV prevention program in Tamilnadu resulted in increased consistent condom use and a decrease in self-reported STI among FSWs exposed to intervention. These findings suggest that HIV prevention programs should aim to saturate coverage among key populations to sustain the gains achieved.

Objective: To compare one-year outcomes of women started on antiretroviral therapy (ART) during pregnancy in the pre-Option B+ era to those in the Option B+ era.

Methods: A retrospective chart review was performed at three sites in Malawi. Women were included in the 'pre-Option B+' cohort if they started ART during pregnancy for a CD4 count < 350 cells/mm³ or WHO 3/4 condition and in the 'Option B+' cohort if they started ART during pregnancy regardless of CD4 count or clinical stage. One-year outcomes were compared using Fisher's exact and ANOVA F-tests.

Results: A higher proportion of women in the pre-Option B+ cohort started ART at WHO stage 3/4 (11.9% versus 1.1%, P < 0.001), switched ART regimens (5.9% versus 0%, P = 0.002), or died in the first year after starting treatment (3.9% versus .5%, P = 0.05). While more women in the Option B+ cohort had poor adherence or defaulted, these differences were not significant.

Conclusions: At our study sites, the transition to Option B+ has been associated with ART initiation in women with less advanced HIV infection, improved medication tolerability, and lower mortality. Further research is needed to better understand outcomes of Option B+.

Young women are an important target group in microbicide research, yet little is known about why they participate and stay in microbicide trials. Our study examined motivations for participating in a Phase I microbicide trial among 61 women ages 18 - 24 years in the continental USA and Puerto Rico. We also examined their perspectives on study participation. Participants underwent a semi-structured in-depth interview in which they were asked about factors that motivated enrollment and their experiences while participating. They also completed a Web-based Computer Assisted Self Interview in which they were asked to rate study burden (1 = low to 4 = high). Factors that motivated enrollment were altruism (29%), compensation (17%), a combination of altruism and compensation (37%) and free medical exams (17%). Factors that encouraged participants to stay in the study were study staff (95%), confirmation of good health (41%), and the opportunity to learn about their bodies (17%). Mean ratings of study burden ranged from 1.83 (having to travel to site) to 2.41 (colposcopy), indicating that participants were not highly bothered by visits or procedures. Although Phase I trials require invasive procedures, participants were not highly bothered by them and recognized them as necessary. Good relationships with staff and clear information about how procedures contribute to study goals may encourage participants to remain in trials. Young women may be motivated to enter microbicide trials by stressing the role they will play in discovering better HIV-prevention methods and highlighting the comprehensive preventive exams they will receive.

We describe an observational study of clinical, virologic and drug resistance profiles in HIV-positive antiretroviral adherent subjects with stable low level viremia (LLV) 50-1,000 copies/mL for more than 12 months. Subjects were followed from time of first detectable viral load (VL). In total, 102 episodes of LLV were detected among 80 individuals. The median (mean, range) HIV copy number at genotyping was 250 (486, <50-3900) copies/mL after 14 (17.9, 0-58) months of LLV. Few patients maintained LLV for the entire 9 year period of observation, with half (52%) experiencing viremic progression following a stable period of LLV either spontaneously or after treatment interruption or failed regimen intensification. In the setting of prolonged periods of sustained LLV, mean duration 22 (range 8 - 106) months, drug resistance (DR) was almost universal. Resistance to ≥1 on-treatment drugs was defined in 97% of specimens and DR to all drugs in the treatment regimen in over half of all patients. Evolution of DR mutations during the period of LLV was observed in 20/28 (71%) subjects with specimens available for follow-up testing. This evolution was associated with viremic progression to levels >1000 copies/mL (p=0.03). Our data suggest that DR present in patients with LLV is likely to impact long term clinical outcomes, highlighting the importance of optimizing techniques to detect the presence of drug resistant HIV in the setting of LLV and the need for larger prospective studies to assess the emergence of DR in the setting of sustained LLV and the impact of this DR on treatment outcomes.