Search

INTRODUCTION AND OBJECTIVE: In May 2018, the World Health Organization and other regulatory authorities released a safety alert for dolutegravir related to a risk of neural tube defects among women exposed to dolutegravir at the time of conception. Models of how drug safety information can be shared effectively in the shortest time are necessary to prevent interruptions of public health programs. We sought to describe an implementation process to inform and support women already on dolutegravir-based regimens at the time of conception to make informed choices following the safety alert of a potential teratogenicity risk. We describe the choices made by women, as well as determine the factors associated with women's choices to switch off dolutegravir.A clinic response plan was developed in the first week following the alert and clinic staff were trained on safety guidance. All women aged 55 years taking dolutegravir were identified from the clinic database and contacted by phone for earlier appointments. Non-menopausal and non-surgically sterilized women were referred for urine pregnancy testing and evaluation of pregnancy intentions in the following 12 months and effective family planning was offered. We describe the coverage of women who received the communication as well as the fidelity to the outlined plan from 21 May to 12 September, 2018. We used modified a Poisson regression analysis to determine factors associated with switching off dolutegravir.Of all active patients in the clinic, 9% (690/7963) were identified as female aged 55 years taking dolutegravir. Ninety-five percent (656/690) were reviewed by September 2018 and informed of the safety alert, implying a high level of uptake. Fidelity to standard operating procedures was also high at 72%. Twenty-two percent (146/656) of patients were menopausal or surgically sterilized. Five hundred and ten women were of reproductive potential with a median age (interquartile range) of 37 years (30-42 years). Five percent (23/510) were human chorionic gonadotrophin positive and all initial ultrasound reports revealed no deformities. Twenty-one percent (108/510) had intentions to conceive and opted to stop taking dolutegravir with 90% (97/108) switching to efavirenz. Seventy-nine percent (402/510) opted to remain taking dolutegravir. However, only 40% (160/402) chose effective contraceptive methods and 60% (242/402) opted for condoms only/no contraceptive method.A rapid well-coordinated response ensured prompt communication of the dolutegravir safety warning. The process developed by the clinic can act as a model for response during drug safety alerts. Women made informed decisions with most opting to remain taking dolutegravir; however, effective contraception uptake was low.

Additional file 1. Multivariable logistic regression model of number of curable STI infections, sociodemographic and clinical characteristics or risk behaviors in men with urethral discharge syndrome in Kampala, Uganda with I) None, and II) Two or more as the referent.

Contains fulltext : 283104.pdf (Publisher’s version ) (Open Access) BACKGROUND: Late initiation of antiretrovirals in pregnancy is associated with increased risk of perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy and safety of dolutegravir-based compared with efavirenz-based regimens in mothers and infants. METHODS: DolPHIN-2 was a randomised, open-label trial. 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 antiretroviral therapy in third trimester were eligible for inclusion. Eligible women were randomly assigned (1:1) to receive either dolutegravir-based (50 mg dolutegravir, 300 mg tenofovir disoproxil fumarate, and either 200 mg emtricitabine in South Africa or 300 mg lamivudine in Uganda) or efavirenz-based (fixed dose combination 600 mg tenofovir disoproxil fumarate plus either emtricitabine in South Africa or lamivudine in Uganda) therapy. The primary efficacy outcome was the time to a viral load of less than 50 copies per mL measured at 6, 12, 24, 48, and 72 weeks postpartum with a Cox model adjusting for viral load and CD4 cell count. Safety endpoints were summarised by the number of women and infants with events. This trial is registered with ClinicalTrials.gov, NCT03249181. FINDINGS: Between Jan 23 and Aug 15, 2018, 280 women were screened for inclusion, of whom 268 (96%) women were randomly assigned: 133 (50%) to the efavirenz group and 135 (50%) to the dolutegravir group. 250 (93%; 125 [50%] in the efavirenz group and 125 [50%] in the dolutegravir group) women were included in the intention-to-treat analysis of efficacy. Median time to viral load of less than 50 copies per mL was 4·1 weeks (IQR 4·0-5·1) in the dolutegravir group compared with 12·1 weeks (10·7-13·3) in the efavirenz group (adjusted hazard ratio [HR] 1·93 [95% CI 1·5-2·5]). At 72 weeks postpartum, 116 (93%) mothers in the dolutegravir group and 114 (91%) in the efavirenz group had a viral load of less than 50 copies per mL. Of 57 (21%) mothers with a severe adverse event, three (2%) in the dolutegravir group and five (4%) in the efavirenz group were related to the drug (dolutegravir drug-related events were one woman each with suicidal ideation, suicide attempt, herpes zoster meningitis; efavirenz drug-related events were one woman each with suicide attempt and liver cirrhosis, and three people with drug-induced liver injury). Of 136 (56%) infants in whom severe adverse events were recorded, none were related to the study drugs. In addition to the three infant HIV infections detected at birth in the dolutegravir group that have been previously reported, an additional transmission in the efavirenz group occurred during breastfeeding despite optimal maternal viral suppression and serial negative infant tests in the first year of life. INTERPRETATION: Dolutegravir was safe and well tolerated, supporting updated WHO treatment recommendations in pregnant and breastfeeding women. Infant HIV transmissions can occur during breastfeeding despite persistently undetectable maternal viral load highlighting the need for continued infant testing. FUNDING: Unitaid.

Background Multi-drug resistant Neisseria gonorrhoeae (NG) threatens the effectiveness of gonorrhea treatment and control globally. Pharyngeal NG (pNG) infections are hypothesized to play a role in the emergence of antimicrobial resistance (AMR) in NG, yet the epidemiology of pNG infections is poorly understood, especially in resource-limited settings (RLS). We report on pNG in men with concurrent urogenital NG infections in Kampala, Uganda. Methods Penile-meatal and pharyngeal samples were collected from Ugandan men with urethral discharge syndrome (UDS), cultured for NG, and tested by nucleic acid amplification tests (NAATs) for NG and other STIs. Antimicrobial susceptibility testing was performed on all NG isolates. Results Of the 83 participants (mean age 29.5 years) who provided urogenital and pharyngeal samples, 22.9% (19/83) were living with HIV, and 57.8% (48/83) were positive for urogenital gonorrhea. NG was detected in 8.6% (7/81) of pharyngeal samples by NAAT; 57.1% (4/7) were also positive by culture. Participants with pNG had concurrent urogenital NG, were HIV-negative, heterosexual (71.4%), reported transactional sex (85.7%), did not report oral sex (85.7%), and were younger (median – 24 years, IQR=21–28; p=0.013) than pNG-negative participants (median – 29 years, IQR=27–32). The paired (n = 4) urogenital-pharyngeal isolates displayed the same antimicrobial susceptibility profile: ciprofloxacin-, tetracycline-, and penicillin-resistant and ceftriaxone- and cefixime-susceptible. None of the pharyngeal samples were positive for Chlamydia trachomatis and one sample was positive for Mycoplasma genitalium. Conclusions To our knowledge, this is the first report of pNG in Ugandan men. NAATs were more sensitive than cultures for detection of pNG. In this pilot study, there was no difference in the susceptibility profiles of paired pharyngeal and urogenital NG isolates. Differences by age might be explained by differences in sexual behaviors or mucosal immunity. Additional studies are warranted to better define the epidemiology and microbiology of pNG infections in RLS.

Background After effective treatment, persons diagnosed with a sexually transmitted infections (STI) are encouraged to modify behavior and notify partners. In resource-limited settings (RLS), follow-up assessment is limited by a variety of factors, including access to knowledge, material resources, and reliable communication. Methods A study conducted in 2019 within the existing WHO-based Enhanced Gonococcal Antimicrobial Surveillance Program (EGASP) collected urogenital samples and blood from men with urethral discharge syndrome (UDS). Samples were tested for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG), and HIV. Participants received treatment and were then followed up using phone calls on days 7, 14 and 21 post-enrolment. Results Of the 250 participants recruited for this study, 66.7%, 20.5%, 11.6%, and 2.0% were positive for NG, CT, MG, TV, respectively, and 20% (50/250) were HIV-positive. Follow-up visits on days 7, 14, and 21 were completed by 98.8%, 96.0%, and 96.4% of participants, respectively. The majority (94.5%) of participants completed their prescribed treatment regimen. Resolution of symptoms (penile discharge and dysuria) was reported by 76.7% of participants 3–5 days post-treatment while 7.5% reported no resolution of symptoms. The majority (77.2%) reported sexual activity while on treatment; 31.6% of those reported condom use, and 15.1% reported multiple partners. PN was reported by 66.9% of participants; 16.8% of participants reported that they had no intention of notifying their partners. Conclusions The prevalence of STIs was high in this group of men with UDS who also reported low condom use and multiple sex partners. While completion rate of follow-up visits was very high, innovative ways to follow-up patients to ensure response to treatment and to incentivize PN are necessary in future STI control interventions.

Effective treatment of sexually transmitted infections (STIs) is limited by diagnostics that cannot deliver results rapidly while the patient is still in the clinic. The gold standard methods for identification of STIs are nucleic acid amplification tests (NAATs), which are too expensive for widespread use and have lengthy turnaround times. To address the need for fast and affordable diagnostics, we have developed a portable, rapid, on-cartridge magnetofluidic purification and testing (PROMPT) polymerase chain reaction (PCR) test. We show that it can detect Neisseria gonorrhoeae, the pathogen causing gonorrhea, with simultaneous genotyping of the pathogen for resistance to the antimicrobial drug ciprofloxacin in