IndexKey points and details of the studyCritique of the studyNext step and implicationsThe global epidemic of human immunodeficiency virus (HIV) infection and the enormous number of deaths and financial losses it causes each year remain a serious public health problem. The distribution of infections around the world 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 area have up to eight times higher incidence rates of HIV-1 infection and a HIV prevalence up to 3.3 times higher than their male counterparts. 1 This indicates that women, especially young women, are much more vulnerable and susceptible to acquiring HIV-1; Effective prevention strategies targeting them are desperately needed. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay The limitations of current prevention strategies require more effective ways to curb the rate of transmission in the generalized epidemic religion. Condom use depends largely on whether women have the power to negotiate with their male partners regarding its use. The percentage of condom use to prevent HIV infection appears to be much lower among regular couples than among sex workers2. A common situation in regular couples in South Africa is that, to sustain emotional and material support from male partners, a girl does not obey her partner's will and chooses not to use condoms or other preventive measures even if she knows the existence of risk3. Therefore, high coverage of free condom distribution does not guarantee high frequency of use in a defined situation due to a combination of social and personal reasons. Even voluntary testing, which has proven effective in informing people about their infection status, has received less than expected support from local people due to discrimination and fear of the disease2. Another example is male circumcision. In many African countries, poor sanitation and poor medical resources make male circumcision inaccessible to normal people, so achieving the proposed HIV prevention effect is not available. Obstacles to the reality of the situation push medical and public health professionals to think about more direct and effective options. Both oral pre-exposure prophylaxis and vaginal microbicides have become new candidates in clinical trials in recent decades. Oral prophylaxis has been found to reduce the risk of HIV-1 infection by 50% or more in several groups, including men who have sex with another man, drug users, and heterosexual men and women in several areas of the world. world4. However, subsequent studies of some pre-exposure prophylaxis, including oral pills and vaginal gel, showed no evidence of prevention of HIV-1 type acquisition in the intervention groups compared to placebo groups1, 4. These studies required subjects to take the pills every day. base or apply the gel every time before coitus during the entire follow-up period, which usually lasts more than 2 years. With such onerous rules, it is understandable that the percentage of participants who can insist on the principles would decrease over time. Low participant compliance was the reasonthe main reason why some studies were stopped, and also the main obstacle in accurately evaluating the effectiveness of the intervention4; willingness to apply vaginal gel or take drugs for oral pre-exposure prophylaxis was inconsistent before and after the start of the study. These indicate that although gel or oral pre-exposure medications have the potential to protect women from acquiring HIV-1 infection, their daily use and coitus-dependent requirements largely limit their impact. sexually active and reproductive African women. Consequently, a more convenient and acceptable product for pre-exposure prophylaxis is still scarce and needed. Based on the enlightenment of previous studies, the vaginal ring was selected as an optimal vehicle for HIV-1 prevention drugs as it can be used in an easy and non-coitus-dependent manner. Once the ring is placed on the vagina, it is not necessary to administer it via adapter within a month and it does not disturb coitus or cause unpleasant sensations to those who use it. These characteristics give the ring the potential to achieve greater adhesion in subjects. It quickly became a promising candidate in clinical trials. Results from phase I and phase II clinical trials demonstrated that intravaginal rings can deliver dapivirine into the vaginal area for one month at concentrations above EC50 (the concentration of a drug that provides a dose response) for HIV- 1. No adverse events or events that may be related to the ring were confirmed, 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, were also elucidated. This helps us judge whether a person has used the ring as directed based on the plasma concentration of dapivirine and the amount remaining in the returned ring. Additionally, in an in vivo experiment, dapivirine was effective in protecting problems from acquiring HIV-16 infection. These previous studies support further development and research on dapivirine vaginal rings for pre-exposure prophylaxis in healthy women. Therefore, if the ring can still work in phase 3, randomized and double-blind studies are of great importance for its final application in the target population. All the results listed above provided good preparation for the study, and after receiving financial support from the foundation, the study was started. Key Points and Details of the Study As for the details of the study, the researchers enrolled over 2,600 women aged 18 and older. to 45 in 4 African countries with a high incidence of HIV infection. Subjects were divided into intervention group and placebo group by block randomization and followed for over 30 months. The vaginal ring containing dapivirine was placed and expected to remain for a full month. A new ring would be distributed 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 adherence is to see whether subjects' plasma dapivirine level has reached a threshold value. The primary endpoint is HIV-1 infection. Based on each participant's person-years before the endpoints or withdrawal, Cox regression was used to analyze whether there was any difference between the groups in the probability of acquiring an infection during the follow-up period of almost 3 years. The risk ratio between the groups was estimated and wereconducted further analyzes in age subgroups. There were two analysis models: one included all data from the 15 sites and another dropped data collected at two of the 15 sites due to low take-up rates. According to 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 those in the intervention group. placebo group; this figure becomes 37% (95% CI: 12%-56%, P=0.007) in the analysis excluding 2 low-adherence sites. Among different age groups, it was observed that women aged 21 years and older have a much 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 reveal that the dapivirine vaginal ring was safe and acceptable to most participants; proved effective in protecting HIV-negative and sexually active women from HIV-1 infection in areas of prevalence. The effectiveness of the prevention effect increased as the membership and retention rate increased. Furthermore, the lack of protection in young women under the age of 21 may be the result of both biological and behavioral characteristics, which need to be further clarified. Criticism of the Study The study has its strengths and limitations. The randomization created a balanced distribution of traits that can be related to the study in both groups, making the results comparable in the two groups; the double-blind design reduced biases of both subjects and investigators due to knowing the state of the experiment, as participants usually behave differently than they would if they knew their true state and the investigator would tend to conduct the study in order to deduce positive results. Furthermore, the participants represent the most vulnerable population to potential HIV-1 infection and come from almost the most widespread area, which constitutes the same context as the future vaginal ring application context. Consequently, the results reported here are very informative in helping us accurately assess the actual potential performance of the intervention. Furthermore, the whole process of the study was conducted in an organized and restricted manner so that the quality of the data could be considered high and reliable. The researchers used two methods to confirm the subjects' adherence, the amount remaining in the returned ring and the plasma concentration of papaverine. They also compared the separate result of the two methods with the combinatorial result on adherence to examine their consistency, ensuring the legitimacy of the chosen methods. Furthermore, 4 weeks after the last visit, subjects were asked to complete a final questionnaire to verify whether they were HIV-1 positive, considering the delay in seroconversion. This step avoided underestimating a certain number of infections. This design and details make the study rational and reasonable. On the other hand, some limitations in design and conduct were observed in this study. The authors stated that the main objective of the study is to investigate the effectiveness and safety of the ring, however, the subjects also received a routine HIV-1 prevention package during the follow-up period . This could mask the effect of the intervention if the degree of use of usual protective services was different between the two groups, meaning that the observed protective effect could be due to less frequent use of usual services in the placebo group or to their greater use in the.