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WHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in second-line therapy is non-inferior to switching to zidovudine.In this prospective, multicentre, open-label, factorial, randomised, non-inferiority trial (NADIA), participants with confirmed HIV first-line treatment failure (HIV-1 RNA ≥1000 copies per mL) were recruited at seven clinical sites in Kenya, Uganda, and Zimbabwe. Following a 2 × 2 factorial design and stratified by site and screening HIV-1 RNA concentration, participants were randomly assigned (1:1:1:1) to receive a 96-week regimen containing either dolutegravir (50 mg once daily) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir once daily) in combination with either tenofovir (300 mg once daily) plus lamivudine (300 mg once daily) or zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily). The NRTI drugs allocated by randomisation were administered orally in fixed-dose combination pills; other drugs were administered orally as separate pills. The previously reported primary outcome was the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 48 weeks. Here, we report the main secondary outcome: the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 96 weeks (non-inferiority margin 12%). We analysed this outcome and safety outcomes in the intention-to-treat population, which excluded only those who were randomly assigned in error and withdrawn before receiving trial drugs. This study was registered at ClinicalTrials.gov, NCT03988452, and is complete.Between July 30 and Dec 18, 2019, we screened 783 patients and enrolled 465. One participant was randomly assigned in error and immediately withdrawn. The remaining 464 participants were randomly assigned to receive either dolutegravir (n=235) or ritonavir-boosted darunavir (n=229) and to receive lamivudine plus either tenofovir (n=233) or zidovudine (n=231). At week 96, 211 (90%) of 235 participants in the dolutegravir group and 199 (87%) of 229 participants in the darunavir group had HIV-1 RNA less than 400 copies per mL (percentage point difference 2·9, 95% CI -3·0 to 8·7), indicating non-inferiority. Nine (4%) participants (all in the dolutegravir group) developed dolutegravir resistance; no participants developed darunavir resistance (p=0·0023). In the other randomised comparison, 214 (92%) of 233 patients in the tenofovir group and 196 (85%) of 231 patients in the zidovudine group had HIV-1 RNA less than 400 copies per mL (percentage point difference 7·0, 95% CI 1·2 to 12·8), showing non-inferiority and indicating the superiority of tenofovir (p=0·019). The proportions of participants with any grade 3-4 adverse event were similar between the dolutegravir (26 [11%]) and darunavir (28 [12%]) groups and between the tenofovir (22 [9%]) and zidovudine (32 [14%]) groups. There were no deaths related to study medication.Dolutegravir-based and darunavir-based regimens maintain good viral suppression during 96 weeks; dolutegravir is non-inferior to darunavir but is at greater risk of resistance in second-line therapy. Tenofovir should be continued in second-line therapy, rather than being switched to zidovudine.Janssen.

We investigated factors associated with loss to follow-up (LTFU) in 24 urban health facilities in Nairobi, Kenya. We conducted a retrospective analysis of routinely collected data to assess factors associated with LTFU in the period October 1, 2016, to June 30, 2017. LTFU was defined as no antiretroviral therapy (ART) refill for ≥90 days and no documentation of transfer, death, or treatment cessation in the patient chart, and if no lapse of ≥90 days between ART refills, patients were considered retained in care. Multivariable logistic regression modeling was used to compute odds ratios and 95% confidence interval (CI) for LTFU. Our analysis included 633 individuals who were LTFU and 13,098 individuals retained in care. Most participants (69.6%) were women, and median age was 33.0 years (interquartile range, 27.2-38.3 years). Median ART duration was shorter among those LTFU (0.4 years) than retained patients (2.5 years

Objective HIV-associated mortality rates in Africa decreased by 10-20% annually in 2003-2011, after the introduction of antiretroviral therapy (ART). We sought to document HIV-associated mortality rates in the general population in Kenya after 2011 in an era of expanded access to ART. Design We obtained data on mortality rates and migration from a health and demographic surveillance system (HDSS) in Gem, western Kenya, and data for HDSS residents aged 15-64 years from home-based HIV counseling and testing (HBCT) rounds in 2011, 2012, 2013, and 2016. Methods Mortality trends were determined among a closed cohort of residents who participated in at least the 2011 round of HBCT. Results Of 32 467 eligible HDSS residents, 22 688 (70%) participated in the 2011 round and comprised the study cohort. All-cause mortality rates declined from 10.0 [95% confidence interval (CI) 8.4-11.7] per 1000 in 2011 to 7.4 (95% CI 5·7-9·0) in 2016, whereas the mortality rate was stable among HIV-uninfected residents, at 5.7 per 1000 person-years. Among HIV-infected residents, mortality rates declined from 30.5 per 1000 in 2011 to 15.9 per 1000 in 2016 (average decline 6% per year). The HIV-infected group receiving ART had higher mortality rates than the HIV-uninfected group [adjusted rate ratio (aRR) 2.8, 95% CI 2.2-3.4], as did the HIV-infected group who did not receive ART (aRR 5.3, 95% CI 4.5-6.2). Conclusions Mortality rates among HIV-infected individuals declined substantially during ART expansion between 2011 and 2016, though less than during early ART introduction. Mortality trends among HIV-infected populations are critical to understanding epidemic dynamics.

Cervical cancer is the second most common cancer among women worldwide. Infection with the human immunodeficiency virus (HIV) and its related immunosuppression are associated with an increased risk of prevalent, incident, and persistent squamous intraepithelial lesions (SILs) of the cervix. The objective of the study was to describe the prevalence and predictors of high-risk HPV and cervical cancer to support the need for strengthening cervical cancer screening programs for HIV infected women in Kenya. A cross sectional study was conducted in a hospital in Central Kenya, Kiambu district. The study population constituted of HIV positive women attending the ART treatment clinic. A total of 715 HIV positive women initiated on Antiretroviral Therapy (ART) were enrolled in this study. About 359 (52.1%) were less than 40 years of age and 644 (90.3%) of the patients were widowed. About 642 (92.6%) of the HIV infected women were in follow-up period of ≥ 1 year. The outcome/prognosis of the patients undergoing ICC was 3 cured, 5 good and 4 poor respectively. In a multivariable ordinal logistic regression analysis showed that for a one-unit decrease of CD4, we expect 1.23 log odds of increasing the severity of cervical cancer (B = 1.23, P0.0 15), given that all of the other variables in the model are held constant. In conclusion screening of all HIV infected women, who are under HIV care and treatment, enrolling patients on HAART with higher CD4 counts is recommended to see the net effect of HAART response.

BACKGROUND: Although used globally little data exist on the efficacy of nevirapine (NVP) used in combination with tenofovir (TDF)/emtricitabine or lamivudine (XTC) and no large randomized prospective control trials exists comparing this combination with efavirenz (EFV)/TDF/(XTC). METHODS: As part of the AIDSRelief program a retrospective review of patient medical chart information along with a cross-sectional viral load and adherence measurement was conducted between 2004 and 2009. An on-treatment analysis excluded patients who died transferred out of care or were lost to follow-up. A switch of antiretrovirals for any reason was considered a failure in the intent-to-treat analysis. Patients with only clinically relevant reasons for switching such as toxicity adverse effects viral failure or clinical/immunological failure lost to follow-up and death were considered failures as part of the modified-intent-to-treat analysis. Step-wise multiple regression analysis was used to identify variables that were associated with viral suppression. RESULTS: A random sample of 3862 patients met criteria and were included in this analysis. In the on-treatment analysis older age (P < 0.004) and baseline CD4