Table of contentsKey points and details of the studyCritique of the studyNext step and implicationsThe global epidemic of HIV (human immunodeficiency virus, HIV) infection and the great The number of deaths and financial losses it causes each year remains a major public health problem. The distribution of infections worldwide is widely differentiated, with more than 80% of the 36.7 million people currently living with HIV and more than two-thirds of the 1.8 million newly infected people coming from sub-Saharan Africa in 20161. Notably, more than half of those currently infected are women, and women aged 15 to 24 in this region had up to eight times higher incidence rates of HIV-1 infection and a higher prevalence HIV infection up to 3.3 times higher than their male counterparts. 1 This indicates that women, particularly young women, are much more vulnerable and susceptible to contracting HIV-1; effective prevention strategies targeted at them are desperately needed. Say no to plagiarism. Get a tailor-made essay on "Why violent video games should not be banned"? Get the original essay The limits of current prevention strategies call for more effective ways to curb the speed of transmission in widespread epidemic religion. Condom use depends largely on women's ability to negotiate their use with their male partners. The percentage of condom use to prevent HIV infection is found to be much lower in regular partnerships than among sex workers2. A common situation in regular partnerships in South Africa is that, in order to receive emotional and material support from her male partners, a girl does not obey her partner's wishes and chooses not to use condom or any other preventive measure, even if she knows of the existence of risk3. Therefore, high coverage of free condom distribution does not guarantee high frequency of use in a defined situation, for a combination of social and personal reasons. Voluntary testing, which has proven effective in informing people of their infection status, has also received less than expected support from the local population due to discrimination and fear of the disease2. Another example is male circumcision. In many countries in Africa, poor sanitary conditions and limited medical resources make male circumcision inaccessible to normal people, so the proposed HIV prevention effect is not available. Obstacles to a realistic situation push medical and public health workers to consider more direct and effective options. Oral pre-exposure prophylaxis and vaginal microbicides have emerged as new candidates in clinical trials in recent decades. Oral prophylaxis has been shown to reduce the risk of HIV-1 infection by 50% or more among several groups, including men who have sex with men, drug users, and heterosexual men and women. in different regions of the world4. However, subsequent trials of some pre-exposure prophylaxis, including oral pills and vaginal gel, showed no evidence of prevention of HIV-1 type acquisition in intervention groups compared to placebo groups1 , 4. These trials required subjects to take the pills daily. base or apply the gel each time before coitus during the entire follow-up period, which lastsusually more than 2 years. With such heavy-handed rules, it is understandable that the percentage of participants able to emphasize the principles declines over time. Low participant compliance was the main reason why some trials were stopped, as well as the main obstacle to accurately assessing the effectiveness of the intervention4; willingness to apply vaginal gel or take oral pre-exposure prophylaxis medications was inconsistent before and after study initiation. These indicate that although pre-exposure medications in gel or oral form have the potential to protect women against HIV-1 infection, their daily use and coitus-dependent needs largely limit their impact. .among sexually active and reproductive African women. Therefore, a more practical and acceptable pre-exposure prophylaxis product is still rare and necessary. Based on previous trial results, the vaginal ring was selected as the optimal carrier for HIV-1 prevention drugs because it can be used simply and effectively. manner not dependent on coitus. Once the ring is placed on the vagina, it does not need to be administered within a month, it does not disrupt coitus and does not cause any feeling of discomfort in users. These characteristics give the ring the potential to achieve greater adhesion from subjects. It quickly became a promising candidate in clinical trials. Results from Phase I and Phase II clinical trials showed that intravaginal rings can deliver dapivirine to the vaginal area for one month at concentrations above the EC50 (the concentration of a drug that gives a half-dose maximum). response) for HIV-1 type. There were no confirmed or possibly related adverse reactions to the ring, indicating that it was safe and well tolerated in healthy HIV-negative women5. The basic pharmacokinetics of dapivirine, which is a non-nucleoside inhibitor of HIV-1 reverse transcriptase, has also been clarified. This helps us determine whether a person used the ring as directed based on the plasma concentration of dapivirine and the residual amount in the returned ring. Additionally, in in vivo experiments, dapivirine was effective in protecting subjects against acquisition of HIV-16 infection. These prior trials support the development and research of dapivirine vaginal rings for pre-exposure prophylaxis in healthy women. Therefore, to know whether the ring can still work in phase 3, double-blind randomized trials are of great importance for its final application in its targeted population. All the results listed above prepared the study well and after receiving financial support from the foundation, the trial was launched. Key Points and Study Details When it comes to study details, investigators recruited more than 2,600 women aged 18 years old. to 45 in 4 African countries with high incidence of HIV infection. Subjects were divided into intervention and placebo groups by block randomization and followed for more than 30 months. The vaginal ring containing dapivirine was placed and was expected to remain in place for an entire month. A new ring would be dispensed after the monthly visit and the used ring would be collected to be tested for residual dapivirine to assess whether the ring has been used continuously over the past month. Another method to assess compliance is to test whether subjects' plasma dapivirine level has reached a certain threshold value. The primary endpoint is infection withthe HIV-1 virus. Based on each participant's person-years before points were terminated or withdrawn, Cox regression was used to analyze whether there was a difference between groups in the probability of acquiring an infection during the follow-up period. almost 3 years old. The risk ratio between groups was estimated and further analysis in age subgroups was conducted. There were two analysis models: one included all data from all 15 sites and the other dropped data collected from two of the 15 sites due to low compliance. Based on data from all sites, women in the intervention group had a 27% (95% CI: 1%-46%, P=0.046) lower incidence rate of HIV-1 acquisition than the intervention group. placebo; this figure increases to 37% (95% CI: 12%-56%, P=0.007) in analysis excluding 2 sites with poor adherence. Among different age groups, women aged 21 or older had significantly better prevention efficacy than younger women, with a hazard ratio of 0.44 (95% CI: 0.29-0. 69, P < 0.001) versus 1.27 (95% CI: 0.69). -2.33, P=0.45) in the younger group. Overall, the study results revealed that the dapivirine vaginal ring was safe and acceptable to most participants; it has been shown to be effective in protecting HIV-negative, sexually active women from HIV-1 infection in high prevalence areas. The effectiveness of the prevention effect increases with the increase in the compliance and retention rate. Furthermore, the lack of protection in young women under 21 years of age may be the result of both biological and behavioral characteristics, which need to be further clarified. Critique of the Study The study has its strengths and limitations. The randomization created a balanced distribution of traits that could be linked to the trial in the two groups, making the results comparable in the two groups; The double-blind design reduced bias on the part of subjects and investigators due to knowing the status of the experiment, because participants generally behave differently than they are if they know their true status, and the investigator would tend to conduct the trial in such a way as to infer positive results. Furthermore, the participants constitute the most vulnerable population for potential HIV-1 infection and come from almost the most prevalent area, which is exactly the same context as the future vaginal ring application context. Therefore, the results presented here are very informative because they help us to accurately assess the very real potential performance of the intervention. Furthermore, the entire process of the study was conducted in an organized and restrained manner so that the quality of the data could be considered high and reliable. The researchers used two methods to confirm subjects' compliance, the residual amount in the inverted ring and the plasma concentration of papaverine. They also compared the separate result of the two methods with their combinatorial result on adherence to examine consistency, ensuring the legitimacy of the chosen pathways. Additionally, 4 weeks after the last visit, subjects were asked to complete a final questionnaire to test whether they were HIV-1 seropositive, given the delay in seroconversion. This step made it possible to avoid underestimation of a certain number of infections. This design and details make the study a rational and reasonable one. On the other hand, some limitations in design and implementation were observed in this study. The authors mentioned that the main goal of the study is to investigate the effectiveness and safety of the ring, but that the.