A combination intervention strategy to improve linkage to and retention in HIV care following diagnosis in Mozambique: A cluster-randomized study

Background: Concerning gaps in the HIV care continuum compromise individual and population health. We evaluated a combination intervention strategy (CIS) targeting prevalent barriers to timely linkage and sustained retention in HIV care in Mozambique. Methods and findings: In this cluster-randomized trial, 10 primary health facilities in the city of Maputo and Inhambane Province were randomly assigned to provide the CIS or the standard of care (SOC). The CIS included point-of-care CD4 testing at the time of diagnosis, accelerated ART initiation, and short message service (SMS) health messages and appointment reminders. A pre–post intervention 2-sample design was nested within the CIS arm to assess the effectiveness of CIS+, an enhanced version of the CIS that additionally included conditional non-cash financial incentives for linkage and retention. The primary outcome was a combined outcome of linkage to care within 1 month and retention at 12 months after diagnosis. From April 22, 2013, to June 30, 2015, we enrolled 2,004 out of 5,327 adults ≥18 years of age diagnosed with HIV in the voluntary counseling and testing clinics of participating health facilities: 744 (37%) in the CIS group, 493 (25%) in the CIS+ group, and 767 (38%) in the SOC group. Fifty-seven percent of the CIS group achieved the primary outcome versus 35% in the SOC group (relative risk [RR]CIS vs SOC = 1.58, 95% CI 1.05–2.39). Eighty-nine percent of the CIS group linked to care on the day of diagnosis versus 16% of the SOC group (RRCIS vs SOC = 9.13, 95% CI 1.65–50.40). There was no significant benefit of adding financial incentives to the CIS in terms of the combined outcome (55% of the CIS+ group achieved the primary outcome, RRCIS+ vs CIS = 0.96, 95% CI 0.81–1.16). Key limitations include the use of existing medical records to assess outcomes, the inability to isolate the effect of each component of the CIS, non-concurrent enrollment of the CIS+ group, and exclusion of many patients newly diagnosed with HIV. Conclusions: The CIS showed promise for making much needed gains in the HIV care continuum in our study, particularly in the critical first step of timely linkage to care following diagnosis

Declining Tuberculosis Incidence Among People Receiving HIV Care and Treatment Services in East Africa, 2007–2012

Background: Antiretroviral therapy (ART) reduces the risk of Tuberculosis (TB) among people living with HIV (PLWH). With ART scale-up in sub-Saharan Africa over the past decade, incidence of TB among PLWH engaged in HIV care is predicted to decline. Methods: We conducted a retrospective analysis of routine clinical data from 168,330 PLWH receiving care at 35 facilities in Kenya, Tanzania, and Uganda during 2003–2012, participating in the East African region of the International Epidemiologic Databases to Evaluate AIDS. Temporal trends in facility-based annual TB incidence rates (per 100,000 person years) among PLWH and country-specific standardized TB incidence ratios using annual population-level TB incidence data from the World Health Organization were computed between 2007 and 2012. We examined patient-level and facility-level factors associated with incident TB using multivariable Cox models. Results: Overall, TB incidence rates among PLWH in care declined 5-fold between 2007 and 2012 from 5960 to 985 per 100,000 person years [P = 0.0003] (Kenya: 7552 to 1115 [P = 0.0007]; Tanzania: 7153 to 635 [P = 0.0025]; Uganda: 3204 to 242 [P = 0.018]). Standardized TB incidence ratios significantly decreased in the 3 countries, indicating a narrowing gap between incidence rates among PLWH and the general population. We observed lower hazards of incident TB among PLWH on ART and/or isoniazid preventive therapy and receiving care in facilities offering TB treatment onsite. Conclusions: Annual TB incidence rates among PLWH significantly declined during ART scale-up but remained higher than the general population. Increasing access to ART and isoniazid preventive therapy and co-location of HIV and TB treatment may further reduce TB incidence among PLWH

Increased prevalence of pregnancy and comparative risk of program attrition among individuals starting HIV treatment in East Africa

Background The World Health Organization now recommends initiating all pregnant women on life-long antiretroviral therapy (ART), yet there is limited information about the characteristics and program outcomes of pregnant women already on ART in Africa. Our hypothesis was that pregnant women comprised an increasing proportion of those starting ART, and that sub-groups of these women were at higher risk for program attrition. Methods and findings We used the International Epidemiology Databases to Evaluate AIDS- East Africa (IeDEA-EA) to conduct a retrospective cohort study including HIV care and treatment programs in Kenya, Uganda, and Tanzania. The cohort consecutively included HIV-infected individuals 13 years or older starting ART 2004–2014. We examined trends over time in the proportion pregnant, their characteristics and program attrition rates compared to others initiating and already receiving ART. 156,474 HIV-infected individuals (67.0% women) started ART. The proportion of individuals starting ART who were pregnant women rose from 5.3% in 2004 to 12.2% in 2014. Mean CD4 cell counts at ART initiation, weighted for annual program size, increased from 2004 to 2014, led by non-pregnant women (annual increase 20 cells/mm3) and men (17 cells/mm3 annually), with lower rates of change in pregnant women (10 cells/mm3 per year) (p<0.0001). There was no significant difference in the cumulative incidence of program attrition at 6 months among pregnant women starting ART and non-pregnant women. However, healthy pregnant women starting ART (WHO stage 1/2) had a higher rate of attrition rate (9.6%), compared with healthy non-pregnant women (6.5%); in contrast among women with WHO stage 3/4 disease, pregnant women had lower attrition (8.4%) than non-pregnant women (14.4%). Among women who initiated ART when healthy and remained in care for six months, subsequent six-month attrition was slightly higher among pregnant women at ART start (3.5%) compared to those who were not pregnant (2.4%), (absolute difference 1.1%, 95% CI 0.7%-1.5%). Conclusions Pregnant women comprise an increasing proportion of those initiating ART in Africa, and pregnant women starting ART while healthy are at higher risk for program attrition than non-pregnant women. As ART programs further expand access to healthier pregnant women, further studies are needed to better understand the drivers of loss among this high risk group of women to optimize retention

Incomplete financial markets and jumps in asset prices

For incomplete financial markets, jumps in both prices and consumption can be unavoidable. We consider pure-exchange economies with infinite horizon, discrete time, uncertainty with a continuum of possible shocks at every date. The evolution of shocks follows a Markov process, and fundamentals depend continuously on shocks. It is shown that: (1) equilibria exist; (2) for effectively complete financial markets, asset prices depend continuously on shocks; and (3) for incomplete financial markets, there is an open set of economies U such that for every equilibrium of every economy in U, asset prices at every date depend discontinuously on the shock at that date

Trends in the clinical characteristics of HIV-infected patients initiating antiretroviral therapy in Kenya, Uganda and Tanzania between 2002 and 2009

East Africa has experienced a rapid expansion in access to antiretroviral therapy (ART) for HIV-infected patients. Regionally representative socio-demographic, laboratory and clinical characteristics of patients accessing ART over time and across sites have not been well described. We conducted a cross-sectional analysis of characteristics of HIV-infected adults initiating ART between 2002 and 2009 in Kenya, Uganda and Tanzania and in the International Epidemiologic Databases to Evaluate AIDS Consortium. Characteristics associated with advanced disease (defined as either a CD4 cell count level of less than 50 cells/mm3 or a WHO Stage 4 condition) at the time of ART initiation and use of stavudine (D4T) or nevirapine (NVP) were identified using a log-link Poisson model with robust standard errors. Among 48,658 patients (69% from Kenya, 22% from Uganda and 9% from Tanzania) accessing ART at 30 clinic sites, the median age at the time of ART initiation was 37 years (IQR: 31-43) and 65% were women. Pre-therapy CD4 counts rose from 87 cells/mm3 (IQR: 26-161) in 2002-03 to 154 cells/mm3 (IQR: 71-233) in 2008-09 (p<0.001). Accessing ART at advanced disease peaked at 35% in 2005-06 and fell to 27% in 2008-09. D4T use in the initial regimen fell from a peak of 88% in 2004-05 to 59% in 2008-09, and a greater extent of decline was observed in Uganda than in Kenya and Tanzania. Self-pay for ART peaked at 18% in 2003, but fell to less than 1% by 2005. In multivariable analyses, accessing ART at advanced immunosuppression was associated with male sex, women without a history of treatment for prevention of mother to child transmission (both as compared with women with such a history) and younger age after adjusting for year of ART initiation and country of residence. Receipt of D4T in the initial regimen was associated with female sex, earlier year of ART initiation, higher WHO stage, and lower CD4 levels at ART initiation and the absence of co-prevalent tuberculosis. Public health ART services in east Africa have improved over time, but the fraction of patients accessing ART with advanced immunosuppression is still high, men consistently access ART with more advanced disease, and D4T continues to be common in most settings. Strategies to facilitate access to ART, overcome barriers among men and reduce D4T use are needed

Characteristics and Outcomes among Older HIV-Positive Adults Enrolled in HIV Programs in Four Sub-Saharan African Countries

Limited information exists on adults ≥50 years receiving HIV care in sub-Saharan Africa. Using routinely-collected longitudinal patient-level data among 391,111 adults ≥15 years enrolling in HIV care from January 2005–December 2010 and 184,689 initiating ART, we compared characteristics and outcomes between older (≥50 years) and younger adults at 199 clinics in Kenya, Mozambique, Rwanda, and Tanzania. We calculated proportions over time of newly enrolled and active adults receiving HIV care and initiating ART who were ≥50 years; cumulative incidence of loss to follow-up (LTF) and recorded death one year after enrollment and ART initiation, and CD4+ response following ART initiation. From 2005–2010, the percentage of adults ≥50 years newly enrolled in HIV care remained stable at 10%, while the percentage of adults ≥50 years newly initiating ART (10% [2005]-12% [2010]), active in follow-up (10% [2005]-14% (2010]), and active on ART (10% [2005]-16% [2010]) significantly increased. One year after enrollment, older patients had significantly lower incidence of LTF (33.1% vs. 32.6%[40–49 years], 40.5%[25–39 years], and 56.3%[15–24 years]; p-value<0.0001), but significantly higher incidence of recorded death (6.0% vs. 5.0% [40–49 years], 4.1% [25–39 years], and 2.8% [15–24 years]; p-valve<0.0001). LTF was lower after vs. before ART initiation for all ages, with older adults experiencing less LTF than younger adults. Among 85,763 ART patients with baseline and follow-up CD4+ counts, adjusted average 12-month CD4+ response for older adults was 20.6 cells/mm3 lower than for adults 25–39 years of age (95% CI: 17.1–24.1). The proportion of patients who are ≥50 years has increased over time and been driven by aging of the existing patient population. Older patients experienced less LTF, higher recorded mortality and less robust CD4+ response after ART initiation. Increased programmatic attention on older adults receiving HIV care in sub-Saharan Africa is warranted

Increasing Support for Contraception as HIV Prevention: Stakeholder Mapping to Identify Influential Individuals and Their Perceptions

BACKGROUND: Voluntary contraceptive use by HIV-positive women currently prevents more HIV-positive births, at a lower cost, than anti-retroviral drug (ARV) regimens. Despite this evidence, most prevention of mother-to-child transmission (PMTCT) programs focus solely on providing ARV prophylaxis to pregnant women and rarely include the prevention of unintended pregnancies among HIV-positive women. METHODOLOGY/PRINCIPAL FINDINGS: To strengthen support for family planning as HIV prevention, we systematically identified key individuals in the field of international HIV/AIDS-those who could potentially influence the issue-and sought to determine their perceptions of barriers to and facilitators for implementing this PMTCT strategy. We used a criteria-based approach to determine which HIV/AIDS stakeholders have the most significant impact on HIV/AIDS research, programs, funding and policy and stratified purposive sampling to conduct interviews with a subset of these individuals. The interview findings pointed to obstacles to strengthening linkages between family planning and HIV/AIDS, including the need for: resources to integrate family planning and HIV services, infrastructure or capacity to provide integrated services at the facility level, national leadership and coordination, and targeted advocacy to key decision-makers. CONCLUSIONS/SIGNIFICANCE: The individuals we identified as having regional or international influence in the field of HIV/AIDS have the ability to leverage an increasingly conducive funding environment and a growing evidence base to address the policy, programmatic and operational challenges to integrating family planning with HIV/AIDS. Fostering greater support for implementing contraception for HIV prevention will require the dedication, collaboration and coordination of many such actors. Our findings can inform a targeted advocacy campaign

A combination strategy for enhancing linkage to and retention in HIV care among adults newly diagnosed with HIV in Mozambique: study protocol for a site-randomized implementation science study

Despite the extraordinary scale up of HIV prevention, care and treatment services in sub-Saharan Africa (SSA) over the past decade, the overall effectiveness of HIV programs has been significantly hindered by high levels of attrition across the HIV care continuum. Data from “real-life” settings are needed on the effectiveness of an easy to deliver package of services that can improve overall performance of the HIV care continuum. We are conducting an implementation science study using a two-arm cluster site-randomized design to determine the effectiveness of a combination intervention strategy (CIS) using feasible, evidence-based, and practical interventions—including (1) point-of-care (POC) CD4 count testing, (2) accelerated antiretroviral therapy initiation for eligible individuals, and (3) SMS reminders for linkage to and retention in care—as compared to the standard of care (SOC) in Mozambique in improving linkage and retention among adults following HIV diagnosis. A pre-post intervention two-sample design is nested within the CIS arm to assess the incremental effectiveness of the CIS plus financial incentives (CIS + FI) compared to the CIS without FI on study outcomes. Randomization is done at the level of the study site, defined as a primary health facility. Five sites are included from the City of Maputo and five from Inhambane Province. Target enrollment is a total of 2,250 adults: 750 in the SOC arm, 750 in the CIS cohort of the intervention arm and 750 in the CIS + FI cohort of the intervention arm (average of 150 participants per site). Participants are followed for 12 months from time of HIV testing to ascertain a combined endpoint of linkage to care within 1 month after testing and retention in care 12 months from HIV test. Cost-effectiveness analyses of CIS compared to SOC and CIS + FI compared to CIS will also be conducted. Study findings will provide evidence on the effectiveness of a CIS and the incremental effectiveness of a CIS + FI in a “real-life” service delivery system in a SSA country severely impacted by HIV. Trial registration: Clinicaltrials.gov, NCT0193008