Background Late initiation of HIV antiretroviral therapy (ART) in pregnancy is associated with not achieving viral suppression before giving birth and increased mother-to-child transmission of HIV. We aimed to investigate virological suppression before giving birth with dolutegravir compared with efavirenz, when initiated during the third trimester. MethodsIn this randomised, open-label trial, DolPHIN-2, we recruited pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating ART in third trimester. Participants were randomly assigned (1:1) to dolutegravir-based or efavirenz-based therapy. HIV viral load was measured 7 days and 28 days after antiretroviral initiation, at 36 weeks' gestation, and at the post-partum visit (0-14 days post partum). The primary efficacy outcome was a viral load of less than 50 copies per mL at the first post-partum visit, and the primary safety outcome was the occurrence of drug-related adverse events in mothers and infants until the post-partum visit. Longer-term follow-up of mothers and infants continues. This study is registered with ClinicalTrials.gov, NCT03249181.Findings Between Jan 23, and Aug 15, 2018, we randomly assigned 268 mothers to dolutegravir (135) or efavirenz (133). All mothers and their infants were included in the safety analysis, and 250 mothers (125 in the dolutegravir group, 125 in the efavirenz group) and their infants in efficacy analyses, by intention-to-treat analyses. The median duration of maternal therapy at birth was 55 days (IQR 33-77). 89 (74%) of 120 in the dolutegravir group had viral loads less than 50 copies per mL, compared with 50 (43%) of 117 in the efavirenz group (risk ratio 1•64, 95% CI 1•31-2•06). 30 (22%) of 137 mothers in the dolutegravir group reported serious adverse events compared with 14 (11%) of 131 in the efavirenz group (p=0•013), particularly surrounding pregnancy and puerperium. We found no differences in births less than 37 weeks and less than 34 weeks gestation (16•4% vs 3•3%, across both groups). Three stillbirths in the dolutegravir group and one in the efavirenz group were considered unrelated to treatment. Three infant HIV infections were detected, all in the dolutegravir group, and were considered likely to be in-utero transmissions.Interpretation Our data support the revision to WHO guidelines recommending the transition to dolutegravir in first-line ART for all adults, regardless of pregnancy or child-bearing potential.Funding Unitaid.
Blue light sensitivity of melatonin suppression and subjective mood and alertness responses in humans is recognized as being melanopsin based. Observations that long-wavelength (red) light can potentiate responses to subsequent short-wavelength (blue) light have been attributed to the bistable nature of melanopsin whereby it forms stable associations with both 11-cis and all-trans isoforms of retinaldehyde and uses light to transition between these states. The current study examined the effect of concurrent administration of blue and red monochromatic light, as would occur in real-world white light, on acute melatonin suppression and subjective mood and alertness responses in humans. Young healthy men (18-35 years; n = 21) were studied in highly controlled laboratory sessions that included an individually timed 30-min light stimulus of blue (λ(max) 479 nm) or red (λ(max) 627 nm) monochromatic light at varying intensities (10(13)-10(14) photons/cm(2)/sec) presented, either alone or in combination, in a within-subject randomized design. Plasma melatonin levels and subjective mood and alertness were assessed at regular intervals relative to the light stimulus. Subjective alertness levels were elevated after light onset irrespective of light wavelength or irradiance. For melatonin suppression, a significant irradiance response was observed with blue light. Co-administration of red light, at any of the irradiances tested, did not significantly alter the response to blue light alone. Under the current experimental conditions, the primary determinant of the melatonin suppression response was the irradiance of blue 479 nm light, and this was unaffected by simultaneous red light administration.
Participants in the current study demonstrated poor knowledge of HPV but the majority of MSM were willing to accept HPV vaccine after consultation; with HIV-infected MSM displaying higher acceptability towards a potential HPV vaccination than HIV-uninfected MSM. MSM who were previously aware of HPV were more likely to be willing to pay for HPV vaccine.
Objective. To classify the infection risk of human papillomavirus (HPV) among human immunodeficiency virus- (HIV-) negative men who have sex with men (MSM) using group-based trajectory modeling (GBTM). Methods. This study collected data on demographic and sexual behavior characteristics by questionnaires at semiannual visits from March 1st, 2016 to December 31th, 2017. Researchers collected anal exfoliated cells to finish HPV testing and blood samples to finish HIV testing at baseline and follow-up visits. Accumulative infection numbers of different types of HPV as the primary outcome and the follow-up visits as the independent predicator to build a GBTM model. Results. There were 500 potentially eligible HIV-negative participants at baseline, 361 (72.2%) of whom were included in this study after screening. Three trajectory groups were identified as the best-fitted GBTM model. Trajectory 1, defined as decreased group (DG) accounted for 44.6% (161/361) of the sample, showed a declining pattern with visits. Trajectory 2, defined as flat group (FG) accounted for 49.6% (179/361) of the sample, showed a flat pattern with visits. Trajectory 3, regarded as the increased group (IG) accounted for 5.8% (21/361) of the sample, showed an uptrend. Compared to the DG, risk factors for the FG included receptive anal intercourse (AOR, 2.24; 95% CI, 1.36-3.71), occasional condom use in anal sex during the past six months (AOR, 1.90; 95% CI, 1.16-3.14), experience of transactional sex with males in the past year (AOR, 3.60; 95% CI, 1.12-11.54), and substance use (AOR, 1.81; 95% CI, 1.08-3.04). Risk factors for the IG included receptive anal intercourse (AOR, 2.81; 95% CI, 1.04-7.70), occasional condom use in anal sex during the past six months (AOR, 3.93; 95% CI, 1.40-11.01), and history of other STIs (AOR, 5.72; 95% CI, 1.40-23.46). Conclusion. The MSM data in this study showed three distinct developmental trajectories (DG, FG, and IG) of HPV infection among HIV-negative MSM, with receptive anal intercourse and occasional condom use in anal sex during the past six months being the risk factors associated with FG and IG.
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