Circulating resistance to first-line HIV drug regimens in sub-Saharan Africa: a sheep in wolf’s clothing?

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START or SMART? Timing of Antiretroviral Therapy Initiation and Cardiovascular Risk for People With Human Immunodeficiency Virus Infection

The Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection (START) study has reinforced the benefits of early initiation of antiretroviral therapy (ART). However, a notable secondary finding from that study was that immediate initiation of ART did not prevent cardiovascular disease (CVD) events (0.17 vs 0.20 events/1000 person-years, P = .65). This result appears to contradict a body of evidence, most notably from the Strategies for Management of Antiretroviral Therapy (SMART) study, which reported a 70% increased hazard of cardiovascular events for those deferring or interrupting treatment. Thus, an important unresolved question is whether the timing of ART impacts CVD risk. In this review, published data on relationships between timing of ART and CVD risk are reviewed. The data support a role for ART in mitigating CVD risk at lower CD4 counts, but data also suggests that, among those initiating therapy early, ART alone appears to suboptimally mitigate CVD risk. Additional interventions to address CVD risk among human immunodeficiency virus-infected populations are likely to be needed

Correlates of physical activity among people living with and without HIV in rural Uganda

BackgroundAntiretroviral therapy (ART) has led to diminishing AIDS-related mortality but a concomitant increase in non-communicable diseases (NCDs) for people with HIV (PWH). Whereas physical activity (PA) has been shown to help prevent NCDs and NCD outcomes in other settings, there are few data on PA and its correlates among PWH in high-endemic settings. We aimed to compare PA by HIV serostatus in rural Uganda.MethodsWe analysed data from the UGANDAC study, an observational cohort including PWH in ambulatory HIV care in Mbarara, Uganda, and age- and gender-matched people without HIV (PWOH). Our primary outcome of interest was PA, which we assessed using the International Physical Activity Questionnaire and considered as a continuous measure of metabolic equivalents in minutes/week (MET-min/week). Our primary exposure of interest was HIV serostatus. We fit univariable and multivariable linear regression models to estimate the relationship between HIV and PA levels, with and without addition of sociodemographic and clinical correlates of PA (MET-min/week). In secondary analyses, we explored relationships restricted to rural residents, and interactions between gender and serostatus.ResultsWe enrolled 309 participants, evenly divided by serostatus and gender. The mean age of PWH was 52 [standard deviation (SD) 7.2] and 52.6 (SD 7.3) for PWOH. In general, participants engaged in high levels of PA regardless of serostatus, with 81.2% (251/309) meeting criteria for high PA. However, PWOH reported higher mean levels of PA met-minutes/week than PWH (9,128 vs 7,152, p ≤ 0.001), and a greater proportion of PWOH (88.3%; 136/154) met the criteria for high PA compared to PWH (74.2%; 115/155). In adjusted models, lower levels of PA persisted among PWH (β = −1,734, 95% CI: −2,645, −824, p ≤ 0.001). Results were similar in a sensitivity analysis limited to people living in rural areas.ConclusionIn a rural Ugandan cohort, PWOH had higher levels of PA than PWH. Interventions that encourage PA among PWH may have a role in improving NCD risk profiles among PWH in the region

Reply to Gautret et al

To the Editor—We thank Gautret et al for their comments and interest in our work. We found it compelling to see the Web of Science data that illustrated the ac-celeration of scholarly publications at the intersection of climate change and vec-tor-borne disease. This trend is perhaps unsurprising, considering that each of the last 3 decades has been successively warm-er at the Earth’s surface than any preced-ing decade since 1850, and well-accepted science has demonstrated the devastating ecologic effects of these changes [1]

High Acceptability for Cell Phone Text Messages to Improve Communication of Laboratory Results with HIV-infected Patients in Rural Uganda: A Cross-sectional Survey Study

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. A supplemental file containing the cell phone survey used in this research is attached below. Note: At the time of writing, David Bangsberg was affiliated with Massachusetts General Hospital, Harvard Medical School, Mbarara University of Science and Technology, and Ragon Institute

Sublingual misoprostol versus intramuscular oxytocin for prevention of postpartum hemorrhage in Uganda: a double-blind randomized non-inferiority trial

Background: Postpartum hemorrhage (PPH) is a leading cause of maternal death in sub-Saharan Africa. Although the World Health Organization recommends use of oxytocin for prevention of PPH, misoprostol use is increasingly common owing to advantages in shelf life and potential for sublingual administration. There is a lack of data about the comparative efficacy of oxytocin and sublingual misoprostol, particularly at the recommended dose of 600 mu g, for prevention of PPH during active management of labor. Methods and Findings: We performed a double-blind, double-dummy randomized controlled non-inferiority trial between 23 September 2012 and 9 September 2013 at Mbarara Regional Referral Hospital in Uganda. We randomized 1,140 women to receive 600 mu g of misoprostol sublingually or 10 IU of oxytocin intramuscularly, along with matching placebos for the treatment they did not receive. Our primary outcome of interest was PPH, defined as measured blood loss >= 500 ml within 24 h of delivery. Secondary outcomes included measured blood loss >= 1,000 ml; mean measured blood loss at 1, 2, and 24 h after delivery; death; requirement for blood transfusion; hemoglobin changes; and use of additional uterotonics. At 24 h postpartum, primary PPH occurred in 163 (28.6%) participants in the misoprostol group and 99 (17.4%) participants in the oxytocin group (relative risk [RR] 1.64, 95% CI 1.32 to 2.05, p<0.001; absolute risk difference 11.2%, 95% CI 6.44 to 16.1). Severe PPH occurred in 20 (3.6%) and 15 (2.7%) participants in the misoprostol and oxytocin groups, respectively (RR 1.33, 95% CI 0.69 to 2.58, p = 0.391; absolute risk difference 0.9%, 95% CI -1.12 to 2.88). Mean measured blood loss was 341.5 ml (standard deviation [SD] 206.2) and 304.2 ml (SD 190.8, p = 0.002) at 2 h and 484.7 ml (SD 213.3) and 432.8 ml (SD 203.5, p<0.001) at 24 h in the misoprostol and oxytocin groups, respectively. There were no significant differences between the two groups in any other secondary outcomes. Women in the misoprostol group more commonly experienced shivering (RR 1.91, 95% CI 1.65 to 2.21, p<0.001) and fevers (RR 5.20, 95% CI 3.15 to 7.21, p = 0.005). This study was conducted at a regional referral hospital with capacity for emergency surgery and blood transfusion. High-risk women were excluded from participation. Conclusions: Misoprostol 600 mu g is inferior to oxytocin 10 IU for prevention of primary PPH in active management of labor. These data support use of oxytocin in settings where it is available. While not powered to do so, the study found no significant differences in rate of severe PPH, need for blood transfusion, postpartum hemoglobin, change in hemoglobin, or use of additional uterotonics between study groups. Further research should focus on clarifying whether and in which sub-populations use of oxytocin would be preferred over sublingual misoprostol

Severe Flooding and Malaria Transmission in the Western Ugandan Highlands: Implications for Disease Control in an Era of Global Climate Change

Background. There are several mechanisms by which global climate change may impact malaria transmission. We sought to assess how the increased frequency of extreme precipitation events associated with global climate change will influence malaria transmission in highland areas of East Africa

Correlates of physical activity among people living with and without HIV in rural Uganda

Background Antiretroviral therapy (ART) has led to diminishing AIDS-related mortality but a concomitant increase in non-communicable diseases (NCDs) for people with HIV (PWH). Whereas physical activity (PA) has been shown to help prevent NCDs and NCD outcomes in other settings, there are few data on PA and its correlates among PWH in high-endemic settings. We aimed to compare PA by HIV serostatus in rural Uganda. Methods We analysed data from the UGANDAC study, an observational cohort including PWH in ambulatory HIV care in Mbarara, Uganda, and age- and gender-matched people without HIV (PWOH). Our primary outcome of interest was PA, which we assessed using the International Physical Activity Questionnaire and considered as a continuous measure of metabolic equivalents in minutes/week (MET-min/week). Our primary exposure of interest was HIV serostatus. We fit univariable and multivariable linear regression models to estimate the relationship between HIV and PA levels, with and without addition of sociodemographic and clinical correlates of PA (MET-min/week). In secondary analyses, we explored relationships restricted to rural residents, and interactions between gender and serostatus. Results We enrolled 309 participants, evenly divided by serostatus and gender. The mean age of PWH was 52 [standard deviation (SD) 7.2] and 52.6 (SD 7.3) for PWOH. In general, participants engaged in high levels of PA regardless of serostatus, with 81.2% (251/309) meeting criteria for high PA. However, PWOH reported higher mean levels of PA met-minutes/week than PWH (9,128 vs 7,152, p ≤ 0.001), and a greater proportion of PWOH (88.3%; 136/154) met the criteria for high PA compared to PWH (74.2%; 115/155). In adjusted models, lower levels of PA persisted among PWH (β = −1,734, 95% CI: −2,645, −824, p ≤ 0.001). Results were similar in a sensitivity analysis limited to people living in rural areas. Conclusion In a rural Ugandan cohort, PWOH had higher levels of PA than PWH. Interventions that encourage PA among PWH may have a role in improving NCD risk profiles among PWH in the region

Disinhibition in Risky Sexual Behavior in Men, but Not Women, during Four Years of Antiretroviral Therapy in Rural, Southwestern Uganda

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