Preventing HIV-1 infection is a high global priority. This study assessed prevention strategies in young women in South Africa, Uganda, and Zimbabwe using oral or vaginal antiretroviral agents. No ...approach was found to be effective. The HIV-1 incidence was 5.7 per 100 person-years.
Daily oral preexposure prophylaxis with 300 mg of tenofovir disoproxil fumarate (TDF), alone or in combination with 200 mg of emtricitabine (FTC) (TDF-FTC Truvada, Gilead Sciences), reduces the risk of acquisition of human immunodeficiency virus type 1 (HIV-1) by 50% or more among persons with high adherence to the regimen, with demonstrated efficacy in men who have sex with men, heterosexuals, and injection-drug users.
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On the basis of these observations, in July 2012 the Food and Drug Administration approved daily treatment with Truvada for the prevention of HIV-1 acquisition, and the Centers for Disease Control and Prevention has issued . . .
Development of HIV-1 prevention methods is a global priority. In this randomized, controlled trial in sub-Saharan Africa, a vaginal ring containing the antiretroviral dapivirine was 27% effective in ...protecting against HIV-1 acquisition.
More than half of the 35 million persons currently living with human immunodeficiency virus type 1 (HIV-1) infection are women. A majority of these women reside in sub-Saharan Africa,
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a region that has some of the highest incidences of HIV-1 infection in any population worldwide.
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The use of antiretroviral medications as pre-exposure prophylaxis is a promising approach to the prevention of HIV-1 acquisition.
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Several clinical trials of the antiretroviral tenofovir showed such protection against HIV-1.
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However, in three trials involving African women, adherence to tenofovir-containing pills and vaginal gels was low, and HIV-1 protection was not shown. . . .
In this study from South Africa, earlier initiation of antiretroviral therapy in patients with newly diagnosed HIV infection and TB was associated with higher rates of the immune reconstitution ...inflammatory syndrome and adverse events but increased AIDS-free survival.
In patients who have infection with the human immunodeficiency virus (HIV) and tuberculosis, antiretroviral therapy (ART) may be initiated at the same time as or soon after the initiation of tuberculosis treatment. However, antiretroviral agents are often deferred until after the intensive phase of tuberculosis treatment because of concern about the immune reconstitution inflammatory syndrome (IRIS),
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a high pill burden, and overlapping side effects
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when three antiretroviral agents are added to the standard four antituberculosis drugs. These challenges may result in interruption or discontinuation of treatment for the acquired immunodeficiency syndrome (AIDS) or tuberculosis, which can lead to drug . . .
BACKGROUND:Evidence is lacking regarding whether vaginal pre-exposure prophylaxis with topical tenofovir (TFV) reduces the risk of rectal HIV acquisition.
SETTING:Bronx, NY.
METHODS:MTN-014 was a ...phase 1, cross-over, randomized sequence trial comparing the cross-compartment pharmacokinetics and pharmacodynamics of daily TFV reduced-glycerin 1% gel after 14 days each of rectal and vaginal application, with directly observed dosing and a 6-week washout period between phases.
RESULTS:Fourteen HIV-uninfected women enrolled; 91% of doses were observed and 13 women completed all study procedures. TFV and TFV diphosphate (TFV-DP) were detected in most samples collected from the dosing compartment. After vaginal dosing, TFV was detected in 10/14 samples of rectal fluid (RF) (median 4.4 ng/sponge) and 1/13 rectal tissue samples (0.2 ng/mg); TFV-DP was detected in 2/13 rectal tissue samples at 59.8 and 76.5 fmol/mg. After rectal dosing, TFV was detected in 9/14 samples of vaginal fluid (median 1.1 ng/swab) and in 6/14 vaginal tissue samples (median below limit of quantification); TFV-DP was detected in 3/14 vaginal tissue samples at 17.3, 87.6, and 77.1 fmol/mg. Neither cervicovaginal lavage fluid nor RF collected 24 hours after rectal or vaginal dosing resulted in a statistically significant suppression of viral replication.
CONCLUSIONS:In this study of 14 days each of vaginal and rectal application of TFV reduced-glycerin 1% gel, we found only a small degree of cross-compartment distribution of TFV in RF and vaginal fluids and no pharmacodynamic activity in ex vivo testing. Although high TFV concentrations in the dosing compartment may be protective, low cross-compartment tissue concentrations are not likely to be protective.
Data science research involves large volumes of data, often derived from unconventional sources. Given the complex nature of big data research, there is a strong need for the development of ethically ...appropriate protocols that are sensitive to the complexities of data science and data sources. While reviews of health research by research ethics committees are necessary from an ethical and legal perspective, complementary advisory committees such as ethics advisory committees could be established to advise on ethics challenges more broadly. In this Perspective, we describe a multidisciplinary ethics advisory committee linked to a data science research hub in sub-Saharan Africa.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although vaginal microbicides for HIV prevention are designed to be female-initiated, male partner influence has been identified as one of the most significant factors impacting women’s willingness ...and ability to use them. As a result, research teams have sought to increase male partner involvement by encouraging
disclosure
of product use to male partners, promoting male partner
engagement
in the study through attendance at the study clinic, and helping women to garner male partner
support
for product use. This paper aims to assess the impact of these three elements of male partner involvement on women’s adherence to the dapivirine vaginal ring during MTN-020/ASPIRE, a phase III randomized placebo-controlled clinical trial involving 2629 women in Malawi, South Africa, Uganda, and Zimbabwe. During the study, 64–80% of participants reported disclosure of ring use at each quarterly visit, and 13% reported that their partners had attended the study clinic at some point during the study. At study exit, 66% reported that their partner was supportive, 18% unsupportive, and 17% were unsure. After adjusting for age, site and time in study, women were more likely to have low ring adherence if they had an unsupportive male partner (aRR 1.29, 95% CI 1.03–1.62). Neither disclosure nor clinic attendance directly predicted ring adherence, but disclosure increased the probability of having a supportive partner (aRRR 24.17, 95% CI 16.38–35.66) or an unsupportive partner (aRRR 4.10, 95% CI 2.70–6.24), relative to an unknown level of partner support. Women were also more likely to have a supportive partner if their partner had attended the clinic (aRRR 3.77, 95% CI 1.36–10.42). This study suggests that although the vaginal ring is relatively discreet, lack of support from male partners remains a relevant barrier to use. Though both disclosure and clinic attendance may increase partner support, disclosure may also increase partner opposition. Interventions to reduce male partner opposition are needed to maximize the potential impact of the ring and other PrEP products for HIV prevention.
BACKGROUNDIn sub-Saharan Africa, there are limited data on the incidence of sexually transmitted infections (STIs) among women, largely because routine screening for asymptomatic infection is not ...performed. We conducted a secondary analysis to measure STI incidence rates and determine risk factors for new STI acquisition among women enrolled in the VOICE trial.
METHODSWe analyzed data from 4843 women screened for chlamydia, gonorrhoea, syphilis, and trichomonas infection at baseline, annually, at interim visits when clinically indicated and at their study termination visit. Risk reduction counseling and condoms were provided throughout the trial.
RESULTSTwenty percent of evaluable participants had one or more curable STIs at baseline. Over 5660 person-years at risk (PYAR) of observation, incidence rates were 13.8% (95% confidence interval CI, 12.7–14.8) PYAR for chlamydia, 3.5% (95% CI, 3.0–4.1) PYAR gonorrhea, 0.1% (95% CI, 0.6–1.1) PYAR syphilis, and 6.6% (95% CI, 5.8–7.2) PYAR trichomoniasis. South African sites had the highest incidence of chlamydia. The Uganda site had the highest incidence of gonorrhoea and syphilis, and Zimbabwe the lowest incidence overall. The majority of these cases were diagnosed at a routine scheduled testing visit. In multivariate analysis, positive baseline STI, younger than 25 years, being unmarried, and some alcohol consumption were associated with acquiring a new STI.
CONCLUSIONSWe observed high rates of STIs during follow up among women in the VOICE study. Women living in human immunodeficiency virus endemic countries should be screened for common STIs.
Persistent use of HIV prevention methods can be a challenge, particularly for some younger women. The long-acting, discreet, woman-centric dapivirine vaginal ring offers promise as a prevention ...method with less user burden, which could support continued use. We assessed dapivirine vaginal ring use to understand adherence patterns and identify characteristics influencing patterns.
Participants enrolled in South Africa in the MTN-020/ASPIRE randomized placebo-controlled trial.
We used group-based trajectory modeling to identify clusters of participants with similar longitudinal patterns of adherence in the last year of participation and potential predictors of group membership. Women with at least 1 year of follow-up were included (n = 626).
Five adherence patterns were identified: (1) consistently high, 34%, (2) consistently moderate, 34%, (3) consistently low, 16%, (4) decreasing, 9%, and (5) increasing, 7%. Women younger than 22 years adjusted odds ratio (AOR) 1.8, 95% confidence interval (CI): 1.0 to 3.0, using an intrauterine device (AOR 3.3, 95% CI: 1.4 to 7.8) or oral contraceptives (AOR 3.9, 95% CI: 1.7 to 8.9), experiencing menses (AOR 1.8, 95% CI: 1.1 to 3.0), and who reported inconsistent condom use (AOR 1.8, 95% CI: 1.0 to 3.3) were more likely to be classified as consistently low compared to consistently high (referent).
Most South African women successfully persisted with a moderate or high level of use. Encouraging ring replacement with completion of menses may help to decrease concerns about hygiene and improve persistence. Associations between contraception and persistent low adherence suggest efforts may be needed to ensure contraceptive method choice does not interfere with ring use.
Adolescent girls and young women (AGYW) in sub-Saharan Africa are disproportionately affected by the HIV epidemic and face an array of challenges using proven behavioral and biomedical prevention ...methods. To address the urgent need for expanding prevention options, we evaluated the baseline preferences of HIV prevention methods among participants enrolled in the MTN-034/REACH crossover trial along with their stated product preference prior to product initiation.
AGYW aged 16-21 years were enrolled at 4 study sites: Cape Town and Johannesburg, South Africa; Kampala, Uganda; and Harare, Zimbabwe and randomly assigned to the sequence of using oral PrEP and the dapivirine ring for 6 months each, followed by a choice period in which they could choose either product (or neither) for an additional six months. Eligible AGYW were HIV-negative, not pregnant and using effective contraception for at least two months prior to enrollment. Descriptive statistics were used to summarize demographic and behavioral data while multinomial analysis was used to determine predictors of stated product preference (ring or oral PrEP).
Of the 247 AGYW enrolled in REACH, 34% were aged 16-17 and 89% had a primary partner.The median age of sexual debut was 16 years and 40% had ever been pregnant. At screening, 35% of participants were diagnosed with a sexually transmitted infection (STI), 39% had an AUDIT-C score associated with harmful drinking and 11% reported intimate partner violence in the past 6 months. Overall, 28% of participants, had CESD-10 scores suggestive of depressive symptoms (≥12) in the past week. At baseline, similar proportions stated a preference for the ring and oral PrEP (38.1% and 40.5% respectively), with 19% of participants stating they preferred both products equally. Only study site was significantly associated with product preference (P<0.05) with AGYW from Johannesburg having higher odds of preferring the ring and those from Kampala having higher odds of preferring both options equally.
We successfully enrolled African AGYW with a clear unmet need for HIV prevention. The balanced preference between the two products suggests that multiple biomedical prevention options may be appealing to this age group and could address their prevention needs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Effective community engagement for the use of large data sets in health research is faced with challenges similar to those in investigator-driven research. The scope of community engagement has ...evolved in highincome countries to embrace citizen science by communities and regulators to build trust in data science research. In South Africa and other low- and middle-income countries, with varying levels of literacy and the influence of pre-existing beliefs and past negative experiences with research, advisory committees of diverse stakeholder composition still have a role to play in protecting the rights of researched communities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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