Person:

Siedner, Mark

Background: Many guidelines recommend adherence counseling prior to initiating antiretrovirals (ARVs), however the additional benefit of pre-therapy counseling visits on early adherence is not known. We sought to assess for a benefit of adherence counseling visits prior to ARV initiation versus adherence counseling during the early treatment period. Methods: We performed a secondary analysis of data from a prospective cohort of HIV-infected patients in Mbarara, Uganda. Adults were enrolled upon initiation of ARVs. Our primary exposure of interest was ARV adherence counseling prior to initiating therapy (versus concurrent with initiation of therapy). Our outcomes of interest were: 1) average adherence >90% in first three months; 2) absence of treatment interruptions >72 hours in first three months; and 3) Viral load >400 copies/ml at the three month visit. We fit univariable and multivariable regression models, adjusted for predictors of ARV adherence, to estimate the association between additional pre-therapy counseling visits and our outcomes. Results: 300 participants had records of counseling, of whom 231 (77%) completed visits prior to initiation of ARVs and 69 (23%) on or shortly after initiation. Median age was 33, 71% were female, and median CD4 was 133 cell/ml. Median 90-day adherence was 95%. Participants who completed pre-therapy counseling visits had longer delays from ARV eligibility to initiation (median 49 vs 14 days, p<0.01). In multivariable analyses, completing adherence counseling prior to ARV initiation was not associated with average adherence >90% (AOR 0.8, 95%CI 0.4–1.5), absence of treatment gaps (AOR 0.7, 95%CI 0.2–1.9), or HIV viremia (AOR 1.1, 95%CI 0.4–3.1). Conclusions: Completion of adherence counseling visits prior to ARV therapy was not associated with higher adherence in this cohort of HIV-infected patients in Uganda. Because mortality and loss-to-follow-up remain high in the pre-ARV period, policy makers should reconsider whether counseling can be delivered with ARV initiation, especially in patients with advanced disease.

Background: Patient-provider communication is a major challenge in resource-limited settings with large catchment areas. Though mobile phone usership increased 20-fold in Africa over the past decade, little is known about acceptability of, perceptions about disclosure and confidentiality, and preferences for cell phone communication of health information in the region. Methods: We performed structured interviews of fifty patients at the Immune Suppression Syndrome clinic in Mbarara, Uganda to assess four domains of health-related communication: a) cell phone use practices and literacy, b) preferences for laboratory results communication, c) privacy and confidentiality, and d) acceptability of and preferences for text messaging to notify patients of abnormal test results. Results: Participants had a median of 38 years, were 56% female, and were residents of a large catchment area throughout southwestern Uganda. All participants expressed interest in a service to receive information about laboratory results by cell phone text message, stating benefits of increased awareness of their health and decreased transportation costs. Ninety percent reported that they would not be concerned for unintended disclosure. A minority additionally expressed concerns about difficulty interpreting messages, discouragement upon learning bad news, and technical issues. Though all respondents expressed interest in password protection of messages, there was also a strong desire for direct messages to limit misinterpretation of information. Conclusions: Cell phone text messaging for communication of abnormal laboratory results is highly acceptable in this cohort of HIV-infected patients in rural Uganda. The feasibility of text messaging, including an optimal balance between privacy and comprehension, should be further studied.

Background: Mobile health (mHealth) technologies hold incredible promise to improve healthcare delivery in resource-limited settings. Network reliability across large catchment areas can be a major challenge. We performed an analysis of network failure frequency as part of a study of real-time adherence monitoring in rural Uganda. We hypothesized that the addition of short messaging service (SMS+GPRS) to the standard cellular network modality (GPRS) would reduce network disruptions and improve transmission of data. Methods: Participants were enrolled in a study of real-time adherence monitoring in southwest Uganda. In June 2011, we began using Wisepill devices that transmit data each time the pill bottle is opened. We defined network failures as medication interruptions of >48 hours duration that were transmitted when network connectivity was re-established. During the course of the study, we upgraded devices from GPRS to GPRS+SMS compatibility. We compared network failure rates between GPRS and GPRS+SMS periods and created geospatial maps to graphically demonstrate patterns of connectivity. Results: One hundred fifty-seven participants met inclusion criteria of seven days of SMS and seven days of SMS+GPRS observation time. Seventy-three percent were female, median age was 40 years (IQR 33–46), 39% reported >1-hour travel time to clinic and 17% had home electricity. One hundred one had GPS coordinates recorded and were included in the geospatial maps. The median number of network failures per person-month for the GPRS and GPRS+SMS modalities were 1.5 (IQR 1.0–2.2) and 0.3 (IQR 0–0.9) respectively, (mean difference 1.2, 95%CI 1.0–1.3, p-value<0.0001). Improvements in network connectivity were notable throughout the region. Study costs increased by approximately $1USD per person-month. Conclusions: Addition of SMS to standard GPRS cellular network connectivity can significantly reduce network connection failures for mobile health applications in remote areas. Projects depending on mobile health data in resource-limited settings should consider this upgrade to optimize mHealth applications.

Background: There is conflicting evidence on the immunologic benefit of treating helminth co-infections (“deworming”) in HIV-infected individuals. Several studies have documented reduced viral load and increased CD4 count in antiretroviral therapy (ART) naïve individuals after deworming. However, there are a lack of data on the effect of deworming therapy on CD4 count recovery among HIV-infected persons taking ART. Methodology/Principal Findings To estimate the association between empiric deworming therapy and CD4 count after ART initiation, we performed a retrospective observational study among HIV-infected adults on ART at a publicly operated HIV clinic in southwestern Uganda. Subjects were assigned as having received deworming if prescribed an anti-helminthic agent between 7 and 90 days before a CD4 test. To estimate the association between deworming and CD4 count, we fit multivariable regression models and analyzed predictors of CD4 count, using a time-by-interaction term with receipt or non-receipt of deworming. From 1998 to 2009, 5,379 subjects on ART attended 21,933 clinic visits at which a CD4 count was measured. Subjects received deworming prior to 668 (3%) visits. Overall, deworming was not associated with a significant difference in CD4 count in either the first year on ART (β = 42.8; 95% CI, −2.1 to 87.7) or after the first year of ART (β = −9.9; 95% CI, −24.1 to 4.4). However, in a sub-analysis by gender, during the first year of ART deworming was associated with a significantly greater rise in CD4 count (β = 63.0; 95% CI, 6.0 to 120.1) in females. Conclusions/Significance: Empiric deworming of HIV-infected individuals on ART conferred no significant generalized benefit on subsequent CD4 count recovery. A significant association was observed exclusively in females and during the initial year on ART. Our findings are consistent with recent studies that failed to demonstrate an immunologic advantage to empirically deworming ART-naïve individuals, but suggest that certain sub-populations may benefit.

Background: The resazurin microtiter assay (classic REMA), a colorimetric liquid culture-based drug susceptibility assay for Mycobacterium tuberculosis (MTB), has been endorsed by the World Health Organization. The assay requires 8-16 days to obtain results, delaying management of drug resistant tuberculosis patients. A modified REMA which allows results in as little as 24 hours for bacterial strains, has been developed and validated using Staphylococcus aureus, but has not yet been evaluated for MTB. Therefore we assessed the performance of the modified REMA for rifampicin (RIF) and isoniazid (INH) susceptibility, using the classic REMA as the reference standard. We also compared simplicity (from the technicians’ point of view), time taken to obtain results (rank-sum testing), specificity and Kappa statistics of the two methods. Results: The modified REMA, which is a one-step procedure, was found to be simpler to perform and results were obtained in a significantly shorter time (5 versus 9 days, p < 0.0001) compared to the classic REMA due to addition of indicator and strain at the same time. The specificity of the modified REMA was low {46.8% (35.5% - 58.4%) for RIF and 13.9% (7.2% - 23.5%) for INH}. Kappa statistics were 16.0% for RIF and 2.0% for INH. Low specificity and kappa statistics are due to indicator reduction by the strains before complete drug activity. Conclusion: Although modified REMA is faster and simpler compared to classic REMA, it is not reliable for MTB drug susceptibility testing.

Background: This study seeks to understand distance from health facilities as a barrier to maternal and child health service uptake within a rural Liberian population. Better understanding the relationship between distance from health facilities and rural health care utilization is important for post–Ebola health systems reconstruction and for general rural health system planning in sub–Saharan Africa. Methods: Cluster–sample survey data collected in 2012 in a very rural southeastern Liberian population were analyzed to determine associations between quartiles of GPS–measured distance from the nearest health facility and the odds of maternal (ANC, facility–based delivery, and PNC) and child (deworming and care seeking for ARI, diarrhea, and fever) service use. We estimated associations by fitting simple and multiple logistic regression models, with standard errors adjusted for clustered data. Findings: Living in the farthest quartile was associated with lower odds of attending 1–or–more ANC checkup (AOR = 0.04, P < 0.001), 4–or–more ANC checkups (AOR = 0.13, P < 0.001), delivering in a facility (AOR = 0.41, P = 0.006), and postnatal care from a health care worker (AOR = 0.44, P = 0.009). Children living in all other quartiles had lower odds of seeking facility–based fever care (AOR for fourth quartile = 0.06, P < 0.001) than those in the nearest quartile. Children in the fourth quartile were less likely to receive deworming treatment (AOR = 0.16, P < 0.001) and less likely (but with only marginal statistical significance) to seek ARI care from a formal HCW (AOR = 0.05, P = 0.05). Parents in distant quartiles more often sought ARI and diarrhea care from informal providers. Conclusions: Within a rural Liberian population, distance is associated with reduced health care uptake. As Liberia rebuilds its health system after Ebola, overcoming geographic disparities, including through further dissemination of providers and greater use of community health workers should be prioritized.

In a Perspective accompanying Bor and colleagues, Alexander Tsai and Mark Siedner discuss the gender gap in ART uptake and HIV mortality in Africa.

Background: Point-of-care tests have the capacity to improve healthcare delivery by reducing costs and delay associated with care. A novel point-of-care immunochromatographic test for dual diagnosis of both HIV and syphilis by detecting IgG, IgM and IgA antibodies to HIV, and specific and recombinant Treponema pallidum antigens has recently been developed, but has not been evaluated in rural field settings. We evaluated the performance of the SD Bioline Syphilis/HIV Duo (Duo) assay at a healthcare center in rural Uganda. Methods: A convenience sample of pregnant women attending Kinoni Health Centre IV from March to May, 2013 was enrolled. Venous blood was collected and centrifuged for plasma isolation. Samples were tested with the Duo assay and compared with the Treponema pallidum hemaglutination assay and paired HIV rapid antibody tests as the reference standards. The ease of use and time required for the Duo assay were also assessed by laboratory technicians. Results: Two hundred twenty women were enrolled with a mean age of 25.00 years (SD 5.41). The sensitivity and specificity of the Duo assay were 100% (95% CI 79.0 – 100%) and 100% (95% CI 97.6 – 100.0) respectively, for syphilis, and, 100% (75.9 – 100%) and 99.5% (96.8 – 99.9%) respectively, for HIV. The duo kit was found to be faster and easier to use than the current HIV and syphilis testing techniques. Conclusion: The sensitivity and specificity of the SD Bioline HIV/Syphilis Duo test were excellent in a field setting in Uganda. The Duo assay should be further evaluated in alternate populations and with point-of-care specimens (e.g. whole blood from finger stick specimens), but shows promise as a tool for improved HIV and syphilis surveillance, diagnosis, and treatment in field settings.

Background: Up to 50 % of HIV-infected persons in sub-Saharan Africa are lost from care between HIV diagnosis and antiretroviral therapy (ART) initiation. Structural barriers, including cost of transportation to clinic and poor communication systems, are major contributors. Methods: We conducted a prospective, pragmatic, before-and-after clinical trial to evaluate a combination mobile health and transportation reimbursement intervention to improve care at a publicly operated HIV clinic in Uganda. Patients undergoing CD4 count testing were enrolled, and clinicians selected a result threshold that would prompt early return for ART initiation or further care. Participants enrolled in the pre-intervention period (January – August 2012) served as a control group. Participants in the intervention period (September 2012 – November 2013) were randomized to receive daily short message service (SMS) messages for up to seven days in one of three formats: 1) messages reporting an abnormal result directly, 2) personal identification number-protected messages reporting an abnormal result, or 3) messages reading “ABCDEFG” to confidentially convey an abnormal result. Participants returning within seven days of their first message received transportation reimbursements (about $6USD). Our primary outcomes of interest were time to return to clinic and time to ART initiation. Results: There were 45 participants in the pre-intervention period and 138 participants in the intervention period (46, 49, and 43 in the direct, PIN, and coded groups, respectively) with low CD4 count results. Median time to clinic return was 33 days (IQR 11–49) in the pre-intervention period and 6 days (IQR 3–16) in the intervention period (P < 0.001); and median time to ART initiation was 47 days (IQR 11–75) versus 12 days (IQR 5–19), (P < 0.001). In multivariable models, participants in the intervention period had earlier return to clinic (AHR 2.32, 95 %CI 1.53 to 3.51) and earlier time to ART initiation (AHR 2.27, 95 %CI 1.38 to 3.72). All three randomized message formats improved time to return to clinic and time to ART initiation (P < 0.01 for all comparisons versus the pre-intervention period). Conclusions: A combination of an SMS laboratory result communication system and transportation reimbursements significantly decreased time to clinic return and time to ART initiation after abnormal CD4 test results. Trial registrations Clinicaltrials.gov NCT01579214, approved 13 April 2012. Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0397-1) contains supplementary material, which is available to authorized users.

Background: In resource-rich areas, risky sexual behavior (RSB) largely diminishes after initiation of anti-retroviral therapy, with notable exceptions among some populations who perceive a protected benefit from anti-retroviral therapy (ART). Yet, there is limited data about long-term trends in risky sexual behavior among HIV-infected people in sub-Saharan Africa after initiation of anti-retroviral therapy. Methods: We administered questionnaires every three months to collect sexual behavior data among patients taking ART in southwestern Uganda over four years of follow-up time. We defined RSB as having unprotected sex with an HIV-negative or unknown status partner, or unprotected sex with a casual partner. We fit logistic regression models to estimate changes in RSB by time on ART, with and without adjustment for calendar year and CD4 count. Results: 506 participants were enrolled between 2005 and 2011 and contributed a median of 13 visits and 3.5 years of observation time. The majority were female (70%) and median age was 34 years (interquartile range 29–39). There was a decrease in the proportion of men reporting RSB from the pre-ART visit to the first post-ART visit (16.2 to 4.3%, p<0.01) but not women (14.1 to 13.3%, p = 0.80). With each year of ART, women reported decreasing RSB (OR 0.85 per year, 95%CI 0.74–0.98, p = 0.03). In contrast, men had increasing odds of reporting RSB with each year of ART to near pre-treatment rates (OR 1.41, 95%CI 1.14–1.74, p = 0.001), which was partially confounded by changes in calendar time and CD4 count (AOR = 1.24, 95%CI 0.92–1.67, p = 0.16). Conclusions: Men in southwestern Uganda reported increasing RSB over four years on ART, to levels approaching pre-treatment rates. Strategies to promote long-term safe sex practices targeted to HIV-infected men on ART might have a significant impact on preventing HIV transmission in this setting.