Search

Background Since the declaration of the 10th Ebola Virus Disease (EVD) outbreak in DRC on 1st Aug 2018, several neighboring countries have been developing and implementing preparedness efforts to prevent EVD cross-border transmission to enable timely detection, investigation, and response in the event of a confirmed EVD outbreak in the country. We describe Uganda’s experience in EVD preparedness. Results On 4 August 2018, the Uganda Ministry of Health (MoH) activated the Public Health Emergency Operations Centre (PHEOC) and the National Task Force (NTF) for public health emergencies to plan, guide, and coordinate EVD preparedness in the country. The NTF selected an Incident Management Team (IMT), constituting a National Rapid Response Team (NRRT) that supported activation of the District Task Forces (DTFs) and District Rapid Response Teams (DRRTs) that jointly assessed levels of preparedness in 30 designated high-risk districts representing category 1 (20 districts) and category 2 (10 districts). The MoH, with technical guidance from the World Health Organisation (WHO), led EVD preparedness activities and worked together with other ministries and partner organisations to enhance community-based surveillance systems, develop and disseminate risk communication messages, engage communities, reinforce EVD screening and infection prevention measures at Points of Entry (PoEs) and in high-risk health facilities, construct and equip EVD isolation and treatment units, and establish coordination and procurement mechanisms. Conclusion As of 31 May 2019, there was no confirmed case of EVD as Uganda has continued to make significant and verifiable progress in EVD preparedness. There is a need to sustain these efforts, not only in EVD preparedness but also across the entire spectrum of a multi-hazard framework. These efforts strengthen country capacity and compel the country to avail resources for preparedness and management of incidents at the source while effectively cutting costs of using a “fire-fighting” approach during public health emergencies.

BACKGROUND Global guidelines recommend preexposure prophylaxis (PrEP) use by women at risk for HIV, including during pregnancy, a period with heightened HIV risk. However, data to support safety of PrEP use during pregnancy are limited, particularly from women using PrEP throughout pregnancy. METHODS In an open-label delivery study of PrEP integrated with ART for high-risk HIV serodiscordant couples in Kenya and Uganda (the Partners Demonstration Project), women who became pregnant while using PrEP were offered the option to continue PrEP throughout pregnancy. We compared pregnancy outcomes and 1-year infant growth from pregnancies with exposure to PrEP throughout pregnancy to those without any exposure, with data from the placebo arm of a prior efficacy trial of PrEP conducted in the same setting. RESULTS Outcomes from 30 women who elected to continue PrEP throughout pregnancy were compared with those from 96 pregnancies among PrEP-unexposed women. There were small nonsignificant decreases in the frequency of pregnancy loss [16.7% PrEP-exposed versus 23.5% PrEP-unexposed, adjusted odds ratio (aOR) = 0.59, P = 0.4] and preterm delivery [0 versus 7.7%, (aOR) = 0.54, exact P = 0.6]. No congenital anomalies occurred among PrEP-exposed infants. PrEP-exposed infants had slightly lower adjusted mean z-scores for length (-1.73 versus -0.79, P = 0.05) and head circumference (0.24 versus 1.07, P = 0.04) 1 month after birth but were comparable to PrEP-unexposed infants in these measurements 1 year after birth. CONCLUSION This first evaluation among women using PrEP throughout pregnancy indicates no greater frequency of adverse pregnancy outcomes or restricted infant growth; these findings support recommendations permitting PrEP use during pregnancy.

African HIV serodiscordant couples often desire pregnancy, despite sexual HIV transmission risk during pregnancy attempts. Pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) reduce HIV risk and can be leveraged for safer conception but how well these strategies are used for safer conception is not known. We conducted an open-label demonstration project of the integrated delivery of PrEP and ART among 1,013 HIV serodiscordant couples from Kenya and Uganda followed quarterly for 2 years. We evaluated fertility intentions, pregnancy incidence, the use of PrEP and ART during peri-conception, and peri-conception HIV incidence. At enrollment, 80% of couples indicated a desire for more children. Pregnancy incidence rates were 18.5 and 18.7 per 100 person years among HIV-uninfected and HIV-infected women, and higher among women who recently reported fertility intention (adjusted odds ratio=3.43, 95% CI 2.38-4.93) in multivariable GEE models. During the 6 months preceding pregnancy, 82.9% of couples used PrEP or ART and there were no HIV seroconversions. In this cohort with high pregnancy rates, integrated PrEP and ART was readily used by HIV serodiscordant couples, including during peri-conception periods. Widespread scale-up of safer conception counseling and services is warranted to respond to strong desires for pregnancy among HIV-affected men and women.

Background For HIV-serodiscordant couples, integrated delivery of antiretroviral therapy (ART) for HIV-positive partners and time-limited pre-exposure prophylaxis (PrEP) for negative partners virtually eliminates HIV transmission. Standardized messaging, sensitive to the barriers and motivators to HIV treatment and prevention, is needed for widespread scale-up of this approach. Methods Within the Partners Demonstration Project, a prospective interventional project among 1013 serodiscordant couples in Kenya and Uganda, we offered ART to eligible HIV-positive partners and PrEP to HIV-negative partners before ART initiation and through the HIV-positive partner's first 6 months of ART use. We conducted individual and group discussions with counseling staff to elicit the health communication framework and key messages about ART and PrEP that were delivered to couples. Results Counseling sessions for serodiscordant couples about PrEP and ART included discussions of HIV serodiscordance, PrEP and ART initiation and integrated use, and PrEP discontinuation. ART messages emphasized daily, lifelong use for treatment and prevention, adherence, viral suppression, resistance, side effects, and safety of ART during pregnancy. PrEP messages emphasized daily dosing, time-limited PrEP use until the HIV-positive partner sustained 6 months of high adherence to ART, adherence, safety during conception, side effects, and other risks for HIV. Conclusions Counseling messages for HIV-serodiscordant couples are integral to the delivery of time-limited PrEP as a "bridge" to ART-driven viral suppression. Their incorporation into programmatic scale-up will maximize intervention impact on the global epidemic.

Background Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings. Methods and Findings Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (≥85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7–6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0–0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP. Conclusions Integrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of 5% per year.

During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.

Introduction: Despite scale-up of antiretroviral therapy (ART) for treating HIV-positive persons, HIV incidence remains elevated among those at high risk such as persons in serodiscordant partnerships. Antiretrovirals taken by HIV-negative persons as pre- exposure prophylaxis (PrEP) has the potential to avert infections in individuals in serodiscordant partnerships. Evaluating the cost-effectiveness of implementing time-limited PrEP as a short-term bridge during the first six months of ART for the HIV- positive partner to prevent HIV transmission compared to increasing ART coverage is crucial to informing policy-makers considering PrEP implementation. Methods: To estimate the real world delivery costs of PrEP, we conducted micro-costing and time and motion analyses in an open-label prospective study of PrEP and ART delivery targeted to high-risk serodiscordant couples in Uganda (the Partners Demonstration Project). The cost (in USD, in 2012) of PrEP and ART for serodiscordant couples was assessed, with and without research components, in the study setting. Using Ministry of Health costs, the cost of PrEP and ART provision within a government programme was estimated, as was the cost of providing PrEP in addition to ART. We parameterized an HIV transmission model to estimate the health and economic impacts of 1) PrEP and ART targeted to high-risk serodiscordant couples in the context of current ARTuse and 2) increasing ARTcoverage to 55% of HIV-positive persons with CD4 5500 cells/mL without PrEP. The incremental cost-effectiveness ratios (ICERs) per HIV infection and disability-adjusted life year (DALY) averted were calculated over 10 years. Results: The annual cost of PrEP and ARTdelivery for serodiscordant couples was $1058 per couple in the study setting and $453 in the government setting. The portion of the programme cost due to PrEP was $408 and $92 per couple per year in the study and government settings, respectively. Over 10 years, a programme of PrEP and ART for high-risk serodiscordant couples was projected to avert 43% of HIV infections compared to current practice with an ICER of $1340 per infection averted. This was comparable to ART expansion alone, which would avert 37% of infections with an ICER of $1452. Conclusions: Using Uganda's gross domestic product per capita of $1681 as a threshold, PrEP and ART for high-risk persons have the potential for synergistic action and are cost-effective in preventing HIV infections in high prevalence settings.The annual cost of PrEP in this programme is less than $100 per serodiscordant couple if implemented in public clinics.

Background Antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) reduce HIV-1 transmission within heterosexual HIV-1 serodiscordant couples. Prioritizing couples at highest HIV-1 transmission risk for ART and PrEP would maximize impact and minimize costs. Methods The Partners Demonstration Project is an open-label, delivery study of integrated PrEP and ART for HIV-1 prevention among high risk HIV-1 serodiscordant couples in Kenya and Uganda. We evaluated the feasibility of using a validated risk score that weighs a combination of easily measurable factors (age, children, marital status, male circumcision status, condom use, plasma HIV-1 levels) to identify couples at highest risk for HIV-1 transmission for enrollment. Couples scoring ≥5 met the risk score eligibility criteria. Results We screened 1694 HIV-1 serodiscordant couples and enrolled 1013. Of the screened couples, 1331 (78.6 %) scored ≥5 (with an expected incidence >3 % per year) and 76 % of these entered the study. The median age of the HIV-1 uninfected partner was 29 years [IQR 26, 36] and 20 % were 50,000 copies/ml. Conclusion A risk scoring tool identified HIV-1 serodiscordant couples for a demonstration project of PrEP and ART with high HIV-1 risk. The tool may be feasible for research and public health settings to maximize efficiency and minimize HIV-1 prevention costs.