Safety and Efficacy of a Dapivirine Vaginal Ring for HIV Prevention in Women.

BACKGROUND: The incidence of human immunodeficiency virus (HIV) infection remains high among women in sub-Saharan Africa. We evaluated the safety and efficacy of extended use of a vaginal ring containing dapivirine for the prevention of HIV infection in 1959 healthy, sexually active women, 18 to 45 years of age, from seven communities in South Africa and Uganda. METHODS: In this randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned participants in a 2:1 ratio to receive vaginal rings containing either 25 mg of dapivirine or placebo. Participants inserted the rings themselves every 4 weeks for up to 24 months. The primary efficacy end point was the rate of HIV type 1 (HIV-1) seroconversion. RESULTS: A total of 77 participants in the dapivirine group underwent HIV-1 seroconversion during 1888 person-years of follow-up (4.1 seroconversions per 100 person-years), as compared with 56 in the placebo group who underwent HIV-1 seroconversion during 917 person-years of follow-up (6.1 seroconversions per 100 person-years). The incidence of HIV-1 infection was 31% lower in the dapivirine group than in the placebo group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.99; P=0.04). There was no significant difference in efficacy of the dapivirine ring among women older than 21 years of age (hazard ratio for infection, 0.63; 95% CI, 0.41 to 0.97) and those 21 years of age or younger (hazard ratio, 0.85; 95% CI, 0.45 to 1.60; P=0.43 for treatment-by-age interaction). Among participants with HIV-1 infection, nonnucleoside reverse-transcriptase inhibitor resistance mutations were detected in 14 of 77 participants in the dapivirine group (18.2%) and in 9 of 56 (16.1%) in the placebo group. Serious adverse events occurred more often in the dapivirine group (in 38 participants [2.9%]) than in the placebo group (in 6 [0.9%]). However, no clear pattern was identified. CONCLUSIONS: Among women in sub-Saharan Africa, the dapivirine ring was not associated with any safety concerns and was associated with a rate of acquisition of HIV-1 infection that was lower than the rate with placebo. (Funded by the International Partnership for Microbicides; ClinicalTrials.gov number, NCT01539226 .)

Petri nets for modeling dynamic characteristics in HOOD

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Kanyimangin: a new 1 million years old sit in West-Turkana, Kenya

The Early to Middle Pleistocene Transition (EMPT 1250-750 ka) is a period characterised by major environmental changes. These changes are reflected in the archaeological and faunal records which are marked by behavioural, cognitive (Acheulean specialisation/expansion) and morphological (encephalisation) innovations within the genus Homo. Unfortunately, the EMPT African hominin fossil record is scarce and poorly correlated with the archaeological record. Here we present faunal and chronometric data of a newly discovered EMPT site in West Turkana: Kanyimangin.In August 2017, the Trans-Evol Project started fieldwork in the floodplain of the Kerio River (Turkana Basin, Kenya), identifying a new palaeontological and archaeological locality. Kanyimangin is located within the Kalabata river (a tributary of the Kerio river) circular anomaly, where ca. 15-meter-deep sediments are preserved from erosion by a series of five sandstones. Although there has been almost no focussed local palaeontological and geochronological study, sediments in that area were believed to be older than 3.7 Ma. However, using combined palaeomagnetism and bio-chronological approaches, we obtain an age estimate between 0.90 and 1.19 Ma. Kanyimangin has yielded substantial lithic (n=344) and faunal (n=2155) assemblages originating partly from buried contexts. The latter comprises 212 individual specimens (NISP) distributed across 20 taxa. The faunal spectrum is composed of both aquatic and terrestrial taxa, including: Palaeoloxodon (Elephas) recki cf. recki, Panthera sp., Hyaena hyaena, Equus grevyi, Rhinocerotidae, Kolpochoerus (limnetes) heseloni, Phacocoerus sp., Hippopotamus amphibius, Syncerus caffer, Aepyceros melampus, Alcephalus buselaphus, cf. Nanger granti and a Renducini as well as the narrow-snouted Euthecodon brumpti, a broad-snouted crocodile, turtles/tortoises, snakes, fish and amphibians. Palaeomagnetic results reveal a normal polarity for the archaeology-bearing sandstone and evidence for a subsequent period of reverse polarity. Together with the presence of Palaeoloxodon recki cf. recki recovered from the same sandstone, this suggests a Matuyama age for the site after the Olduvai subchron. To date, most faunal remains were recovered from survey, which limits their biostratigraphic potential; however, the presence of well-fossilised Phacochoerus sp. and Alcephalus buselaphus specimens recovered on the surface of the archaeology-bearing sandstone equally suggests a Jaramillo (1.06–0.90 Ma) or Cobb Mountain (1.19 Ma) age for the site

Safety, adherence, and HIV-1 seroconversion among women using the dapivirine vaginal ring (DREAM) : an open-label, extension study

BACKGROUND : The Ring Study, a phase 3 trial in 1959 sexually active women (randomised 2:1), showed a favourable safety profile and a 31% HIV-1 infection risk reduction for a vaginal ring containing 25 mg of dapivirine, compared with a placebo ring. We report here the DREAM study, which aimed to evaluate safety, adherence, and HIV-1 incidence in those using the dapivirine vaginal ring (DVR) in open-label use. METHODS : The DREAM study is an open-label extension of The Ring Study, done at five research centres in South Africa and one research centre in Uganda. Former participants from The Ring Study, who remained HIV-negative and who did not discontinue the study due to an adverse event or safety concern that was considered to be related to the investigational product, were eligible. Women who were pregnant, planning to become pregnant, or breastfeeding at screening for DREAM were excluded. All participants received the DVR for insertion at the enrolment visit. Participants attended a 1-month follow-up visit and could either proceed with visits once every 3 months or attend monthly visits up to month 3 and then continue with visits once every 3 months. At each visit, HIV testing and safety evaluations were done, and residual dapivirine measured in used rings (approximately 4 mg is released from the DVR over 28 days of consistent use). HIV-1 incidence was compared descriptively with the simulated incidence rate obtained from bootstrap sampling of participants in the placebo group of The Ring Study, matched for research centre, age, and presence of sexually transmitted infections at enrolment. This study is registered with ClinicalTrials.gov, NCT02862171. FINDINGS : Between July 12, 2016, and Jan 11, 2019, 1034 former participants from The Ring Study were screened, 941 were enrolled and 848 completed the trial. 616 (65·5%) of 941 participants reported treatment-emergent adverse events. Of these, six (0·6%) had events considered to be treatment-related. No treatment-related serious adverse events were reported. Measurements of monthly ring residual amounts in participants enrolled in both trials showed consistently lower mean values in DREAM than in The Ring Study. Arithmetic mean ring residual amounts of participants in The Ring Study DVR group who enrolled in DREAM were 0·25 mg lower (95% CI 0·03–0·47; p=0·027) than the mean ring residual amounts of these participants in The Ring Study. 18 (1·9%) HIV-1 infections were confirmed during DVR use, resulting in an incidence of 1·8 (95% CI 1·1–2·6) per 100 person-years, 62% lower than the simulated placebo rate. INTERPRETATION : Although efficacy estimation is limited by the absence of a placebo group, the observed low HIV-1 incidence and improved adherence observed in DREAM support the hypothesis that increased efficacy due to improved adherence occurs when women know the demonstrated safety and efficacy of the DVR. The feasibility of a visit schedule of once every 3 months was shown, indicating that the DVR can be used in a real-world situation in usual clinical practice.The Ministry of Foreign Affairs (MFA) Denmark, Flanders MFA, Irish Aid, Dutch MFA, UK Aid from the UK Government’s Foreign, Commonwealth and Development Office, and the US President’s Emergency Plan for AIDS Relief through the US Agency for International Development.https://www.thelancet.com/journals/lanhiv/homeam2022Family Medicin

Kanyimangin: the Early to Middle Pleistocene Transition in the south-west of the Turkana Basin

International audienceThe Early to Middle Pleistocene Transition (EMPT) is characterised by major environmental changes and evolutionary innovations within the genus Homo but the scarcity of the African EMPT fossil and archaeological records obscures its palaeoecological context. Here, we present archaeological and faunal evidence from a newly excavated West-Turkana EMPT site—Kanyimangin