Universal Testing, Expanded Treatment, and Incidence of HIV Infection in Botswana.

BACKGROUND: The feasibility of reducing the population-level incidence of human immunodeficiency virus (HIV) infection by increasing community coverage of antiretroviral therapy (ART) and male circumcision is unknown. METHODS: We conducted a pair-matched, community-randomized trial in 30 rural or periurban communities in Botswana from 2013 to 2018. Participants in 15 villages in the intervention group received HIV testing and counseling, linkage to care, ART (started at a higher CD4 count than in standard care), and increased access to male circumcision services. The standard-care group also consisted of 15 villages. Universal ART became available in both groups in mid-2016. We enrolled a random sample of participants from approximately 20% of households in each community and measured the incidence of HIV infection through testing performed approximately once per year. The prespecified primary analysis was a permutation test of HIV incidence ratios. Pair-stratified Cox models were used to calculate 95% confidence intervals. RESULTS: Of 12,610 enrollees (81% of eligible household members), 29% were HIV-positive. Of the 8974 HIV-negative persons (4487 per group), 95% were retested for HIV infection over a median of 29 months. A total of 57 participants in the intervention group and 90 participants in the standard-care group acquired HIV infection (annualized HIV incidence, 0.59% and 0.92%, respectively). The unadjusted HIV incidence ratio in the intervention group as compared with the standard-care group was 0.69 (P = 0.09) by permutation test (95% confidence interval [CI], 0.46 to 0.90 by pair-stratified Cox model). An end-of-trial survey in six communities (three per group) showed a significantly greater increase in the percentage of HIV-positive participants with an HIV-1 RNA level of 400 copies per milliliter or less in the intervention group (18 percentage points, from 70% to 88%) than in the standard-care group (8 percentage points, from 75% to 83%) (relative risk, 1.12; 95% CI, 1.09 to 1.16). The percentage of men who underwent circumcision increased by 10 percentage points in the intervention group and 2 percentage points in the standard-care group (relative risk, 1.26; 95% CI, 1.17 to 1.35). CONCLUSIONS: Expanded HIV testing, linkage to care, and ART coverage were associated with increased population viral suppression. (Funded by the President's Emergency Plan for AIDS Relief and others; Ya Tsie ClinicalTrials.gov number, NCT01965470.).

The Effect of High- and Low-Damping Prosthetic Foot Structures on Knee Loading in the Uninvolved Limb Across Different Walking Speeds.

Lower limb amputation has been associated with secondary impairments such as knee osteoarthritis in the uninvolved limb. Greater knee loading in the frontal plane has been related to severity and rate of progression in knee osteoarthritis. Reduced push-off work from the involved limb can increase uninvolved limb knee loading. However, little is known about specific effects that prosthetic foot damping may have on uninvolved limb loading. We hypothesized that uninvolved limb peak knee internal abduction moment (IAM) and loading rates would be greater when using a high-damping foot compared with a low-damping foot, across walking speeds. Eight healthy, young subjects walked in a prosthesis simulator boot using the experimental feet. Greater uninvolved limb first peak IAM (+16% in fast speed, P = .002; +11% in slow speed, P = .001) and loading rates (+11% in fast speed, P = .003) were observed when using the high-damping foot compared with low-damping foot. Within each foot, uninvolved limb first peak IAM and loading rates had a trend to increase with increased walking speed. These findings suggest that damping properties of prosthetic feet are related to uninvolved limb peak knee IAM and loading rates.

Outcomes of kidney transplantation in HIV-infected recipients.

BACKGROUND: The outcomes of kidney transplantation and immunosuppression in people infected with human immunodeficiency virus (HIV) are incompletely understood. METHODS: We undertook a prospective, nonrandomized trial of kidney transplantation in HIV-infected candidates who had CD4+ T-cell counts of at least 200 per cubic millimeter and undetectable plasma HIV type 1 (HIV-1) RNA levels while being treated with a stable antiretroviral regimen. Post-transplantation management was provided in accordance with study protocols that defined prophylaxis against opportunistic infection, indications for biopsy, and acceptable approaches to immunosuppression, management of rejection, and antiretroviral therapy. RESULTS: Between November 2003 and June 2009, a total of 150 patients underwent kidney transplantation; survivors were followed for a median period of 1.7 years. Patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively, and the corresponding mean graft-survival rates were 90.4% and 73.7%. In general, these rates fall somewhere between those reported in the national database for older kidney-transplant recipients (≥65 years) and those reported for all kidney-transplant recipients. A multivariate proportional-hazards analysis showed that the risk of graft loss was increased among patients treated for rejection (hazard ratio, 2.8; 95% confidence interval [CI], 1.2 to 6.6; P=0.02) and those receiving antithymocyte globulin induction therapy (hazard ratio, 2.5; 95% CI, 1.1 to 5.6; P=0.03); living-donor transplants were protective (hazard ratio, 0.2; 95% CI, 0.04 to 0.8; P=0.02). A higher-than-expected rejection rate was observed, with 1-year and 3-year estimates of 31% (95% CI, 24 to 40) and 41% (95% CI, 32 to 52), respectively. HIV infection remained well controlled, with stable CD4+ T-cell counts and few HIV-associated complications. CONCLUSIONS: In this cohort of carefully selected HIV-infected patients, both patient- and graft-survival rates were high at 1 and 3 years, with no increases in complications associated with HIV infection. The unexpectedly high rejection rates are of serious concern and indicate the need for better immunotherapy. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00074386.).

Novel method to evaluate angular stiffness of prosthetic feet from linear compression tests.

Lower limb amputee gait during stance phase is related to the angular stiffness of the prosthetic foot, which describes the dependence of ankle torque on angular progression of the shank. However, there is little data on angular stiffness of prosthetic feet, and no method to directly measure it has been described. The objective of this study was to derive and evaluate a method to estimate the angular stiffness of prosthetic feet using a simple linear compression test. Linear vertical compression tests were performed on nine configurations of an experimental multicomponent foot (with known component stiffness properties and geometry), which allowed for parametric adjustment of hindfoot and forefoot stiffness properties and geometries. Each configuration was loaded under displacement control at distinct pylon test angles. Angular stiffness was calculated as a function of the pylon angle, normal force, and center of pressure (COP) rate of change with respect to linear displacement. Population root mean square error (RMSE) between the measured and predicted angular stiffness values for each configuration of the multicomponent foot was calculated to be 4.1 N-m/deg, dominated by a bias of the estimated values above the predicted values of 3.8 ± 1.6 N-m/deg. The best-fit line to estimated values was approximately parallel to the prediction, with R2 = 0.95. This method should be accessible for a variety of laboratories to estimate angular stiffness of experimental and commercially available prosthetic feet with minimal equipment.

Changes in clearance, volume and bioavailability of immunosuppressants when given with HAART in HIV-1 infected liver and kidney transplant recipients.

Solid organ transplantation in human immunodeficiency virus 1 (HIV)-infected individuals requiring the concomitant use of immunosuppressants (IS) [e.g. cyclosporine (CsA) or tacrolimus (TAC)] and antiretrovirals (ARVs) [e.g. protease inhibitors (PIs) and/or non-nucleoside reverse transcriptase inhibitors (NNRTIs)] is complicated by significant drug interactions. This paper describes the pharmacokinetics of CsA and TAC in 52 patients on both IS and NNRTIs, PIs or combined NNRTIs + PIs, in studies conducted at 2 weeks, 3, 6, 12 and 24 months after transplantation. Cyclosporine and TAC blood concentrations were measured by LC/MS/MS. This multisubject, varied ARV-IS drug combination, longitudinal observational patient study provided a unique opportunity to examine the effect of different ARV drugs on IS pharmacokinetics (PK) by comparing the ratios of parameters over time and between PK parameters. Subjects taking concomitant PIs exhibited increases in CsA and TAC exposure (AUC/dose) due to the increased apparent oral bioavailability and decreased apparent oral clearance. Those subjects taking CsA and concomitant efavirenz (EFV) showed time dependent increases in exposure due to ~30% increases in the apparent oral bioavailability over time as well as a decreased apparent oral clearance, while subjects on TAC and EFV showed time-dependent changes in all PK parameters. The increased bioavailability was not observed in patients on CsA and nevirapine (NVP). These differences between IS drugs and the changes in PK parameters are not easily predicted, illustrating the importance of continued therapeutic drug monitoring in patients on these complex medication regimens. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection.

Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV-coinfected patients and 2 control groups: 235 HCV-monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3-year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%-71%] and 53% (95% CI = 40%-64%) for the HCV/HIV patients and 79% (95% CI = 72%-84%) and 74% (95% CI = 66%-79%) for the HCV-infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney-liver transplantation (HR = 3.8), an anti-HCV-positive donor (HR = 2.5), and a body mass index < 21 kg/m(2) (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV-coinfected LT patients versus HCV-monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV-coinfected recipients versus HCV-infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes.

Preventing human immunodeficiency virus infection among sexual assault survivors in Cape Town, South Africa: an observational study.

We describe 131 South African sexual assault survivors offered HIV post-exposure prophylaxis (PEP). While the median days completed was 27 (IQR 27, 28), 34% stopped PEP or missed doses. Controlling for baseline symptoms, PEP was not associated with symptoms (OR = 1.30, 95% CI = 0.66, 2.64). Factors associated with unprotected sex included prior unprotected sex (OR = 6.46, 95% CI = 3.04, 13.74), time since the assault (OR = 1.33, 95% CI = 1.12, 1.57) and age (OR = 1.30, 95% CI = 1.08, 1.57). Trauma counseling was protective (OR = 0.18, 95% CI = 0.05, 0.58). Four instances of seroconversion were observed by 6 months (risk = 3.7%, 95% CI = 1.0, 9.1). Proactive follow-up is necessary to increase the likelihood of PEP completion and address the mental health and HIV risk needs of survivors. Adherence interventions and targeted risk reduction counseling should be provided to minimize HIV acquisition.

HIV-infected hospitalized patients with 2009 pandemic influenza A (pH1N1)--United States, spring and summer 2009.

We describe the clinical findings of HIV-infected patients hospitalized with 2009 pandemic influenza A (pH1N1). Data were derived from 3 separate case series in the United States. Among 911 adults hospitalized with pH1N1 influenza, 31 (3.4%) were HIV infected compared with an HIV prevalence of 0.45% in the general US adult population. HIV-infected influenza patients experienced similar rates of intensive care unit admission (29% vs 34%) and death (13% vs 13%) compared with non-HIV-infected patients. Among HIV-infected patients with available data, 14 (50%) of 28 patients had a CD4 cell count <200 cells/µL, which was not associated with an increased risk of an intensive care unit admission or death. Overall, 25 (81%) HIV-infected patients received influenza antiviral therapy, but treatment was initiated within 48 h of illness onset in only 33% of cases. Clinicians should consider early empiric influenza antiviral treatment in HIV-infected patients presenting with suspected influenza.

A randomized noninferiority trial of standard versus enhanced risk reduction and adherence counseling for individuals receiving post-exposure prophylaxis following sexual exposures to HIV.

BACKGROUND: The National HIV/AIDS Strategy proposes to scale-up post-exposure prophylaxis (PEP). Intensive risk reduction and adherence counseling appear to be effective but are resource intensive. Identifying simpler interventions that maximize the HIV prevention potential of PEP is critical. METHODS: A randomized noninferiority study comparing 2 (standard) or 5 (enhanced) risk reduction counseling sessions was performed. Adherence counseling was provided in the enhanced arm. We measured changes in unprotected sexual intercourse acts at 12 months, compared with baseline; HIV acquisition; and PEP adherence. Outcomes were stratified by degree of baseline risk. RESULTS: We enrolled 457 individuals reporting unprotected intercourse within 72 h with an HIV-infected or at-risk partner. Participants were 96% male and 71% white. There were 1.8 and 2.3 fewer unprotected sex acts in the standard and enhanced groups. The maximum potential risk difference, reflected by the upper bound of the 95% confidence interval, was 3.9 acts. The difference in the riskier subset may have been as many as 19.6 acts. The incidence of HIV seroconversion was 2.9% and 2.6% among persons randomized to standard and enhanced counseling, respectively, with a maximum potential difference of 3.4%. The absolute and maximal HIV seroconversion incidence was 9.9% and 20.4% greater in the riskier group randomized to standard, compared with enhanced, counseling. Adherence outcomes were similar, with noninferiority in the lower risk group and concerning differences among the higher-risk group. CONCLUSIONS: Risk assessment is critical at PEP initiation. Standard counseling is only noninferior for individuals with lower baseline risk; thus, enhanced counseling should be targeted to individuals at higher risk.

MELD score is an important predictor of pretransplantation mortality in HIV-infected liver transplant candidates.

BACKGROUND & AIMS: Human immunodeficiency virus (HIV) infection accelerates liver disease progression in patients with hepatitis C virus (HCV) and could shorten survival of those awaiting liver transplants. The Model for End-Stage Liver Disease (MELD) score predicts mortality in HIV-negative transplant candidates, but its reliability has not been established in HIV-positive candidates. METHODS: We evaluated predictors of pretransplantation mortality in HIV-positive liver transplant candidates enrolled in the Solid Organ Transplantation in HIV: Multi-Site Study (HIVTR) matched 1:5 by age, sex, race, and HCV infection with HIV-negative controls from the United Network for Organ Sharing. RESULTS: Of 167 HIVTR candidates, 24 died (14.4%); this mortality rate was similar to that of controls (88/792, 11.1%, P = .30) with no significant difference in causes of mortality. A significantly lower proportion of HIVTR candidates (34.7%) underwent liver transplantation, compared with controls (47.6%, P = .003). In the combined cohort, baseline MELD score predicted pretransplantation mortality (hazard ratio [HR], 1.27; P < .0001), whereas HIV infection did not (HR, 1.69; P = .20). After controlling for pretransplantation CD4(+) cell count and HIV RNA levels, the only significant predictor of mortality in the HIV-infected subjects was pretransplantation MELD score (HR, 1.2; P < .0001). CONCLUSIONS: Pretransplantation mortality characteristics are similar between HIV-positive and HIV-negative candidates. Although lower CD4(+) cell counts and detectable levels of HIV RNA might be associated with a higher rate of pretransplantation mortality, baseline MELD score was the only significant independent predictor of pretransplantation mortality in HIV-infected liver transplant candidates.

Validation of a new method for finding the rotational axes of the knee using both marker-based roentgen stereophotogrammetric analysis and 3D video-based motion analysis for kinematic measurements.

In a previous paper, we reported the virtual axis finder, which is a new method for finding the rotational axes of the knee. The virtual axis finder was validated through simulations that were subject to limitations. Hence, the objective of the present study was to perform a mechanical validation with two measurement modalities: 3D video-based motion analysis and marker-based roentgen stereophotogrammetric analysis (RSA). A two rotational axis mechanism was developed, which simulated internal-external (or longitudinal) and flexion-extension (FE) rotations. The actual axes of rotation were known with respect to motion analysis and RSA markers within ± 0.0006 deg and ± 0.036 mm and ± 0.0001 deg and ± 0.016 mm, respectively. The orientation and position root mean squared errors for identifying the longitudinal rotation (LR) and FE axes with video-based motion analysis (0.26 deg, 0.28 m, 0.36 deg, and 0.25 mm, respectively) were smaller than with RSA (1.04 deg, 0.84 mm, 0.82 deg, and 0.32 mm, respectively). The random error or precision in the orientation and position was significantly better (p=0.01 and p=0.02, respectively) in identifying the LR axis with video-based motion analysis (0.23 deg and 0.24 mm) than with RSA (0.95 deg and 0.76 mm). There was no significant difference in the bias errors between measurement modalities. In comparing the mechanical validations to virtual validations, the virtual validations produced comparable errors to those of the mechanical validation. The only significant difference between the errors of the mechanical and virtual validations was the precision in the position of the LR axis while simulating video-based motion analysis (0.24 mm and 0.78 mm, p=0.019). These results indicate that video-based motion analysis with the equipment used in this study is the superior measurement modality for use with the virtual axis finder but both measurement modalities produce satisfactory results. The lack of significant differences between validation techniques suggests that the virtual sensitivity analysis previously performed was appropriately modeled. Thus, the virtual axis finder can be applied with a thorough understanding of its errors in a variety of test conditions.

Hierarchy of qualities in global health partnerships: a path towards equity and sustainability.

Despite the exponential growth of global health partnerships (GHPs) over the past 20 years, evidence for their effectiveness remains limited. Furthermore, many partnerships are dysfunctional as a result of inequitable partnership benefits, low trust and accountability and poor evaluation and quality improvement practices. In this article, we describe a theoretical model for partnerships developed by seven global health experts. Through semistructured interviews and an open-coding approach to data analysis, we identify 12 GHP pillars spanning across three interconnected partnership levels and inspired by Maslow's hierarchy of needs. The transactional pillars are governance, resources and expertise, power management, transparency and accountability, data and evidence and respect and curiosity. The collaborative pillars (which build on the transactional pillars) are shared vision, relationship building, deep understanding and trust. The transformational pillars (which build on the collaborative pillars and allow partnerships to achieve their full potential) are equity and sustainability. The theoretical model described in this article is complemented by real-life examples, which outline both the cost incurred when GHPs fail to live up to these pillars and the benefits gained when GHPs uphold them. We also provide lessons learnt and best practices that GHPs should adopt to further increase their strength and improve their effectiveness in the future. To continue improving health outcomes and reducing health inequities globally, we need GHPs that are transformational, not just rhetorically but de facto. These actualised partnerships should serve as a catalyst for the greater societal good and not simply as a platform to accrue and exchange organisational benefits.

To achieve 95-95-95 targets we must reach men and youth: High level of knowledge of HIV status, ART coverage, and viral suppression in the Botswana Combination Prevention Project through universal test and treat approach.

BACKGROUND: Increasing HIV treatment coverage is crucial to reducing population-level HIV incidence. METHODS: The Botswana Combination Prevention Project (BCPP) was a community randomized trial examining the impact of multiple prevention interventions on population-level HIV incidence and was conducted from October 2013 through June 2017. Home and mobile campaigns offered HIV testing to all individuals ≥ age 16. All identified HIV-positive persons who were not on antiretroviral therapy (ART) were referred to treatment and tracked to determine linkage to care, ART status, retention in treatment, and viral suppression. RESULTS: Of an estimated total of 14,270 people living with HIV (PLHIV) residing in the 15 intervention communities, BCPP identified 13,328 HIV-positive persons (93%). At study start, 10,703 (80%) of estimated PLHIV knew their status; 2,625 (20%) learned their status during BCPP, a 25% increase with the greatest increases occurring among men (37%) and youth (77%). At study start, 9,258 (65%) of estimated PLHIV were on ART. An additional 3,001 persons started ART through the study. By study end, 12,259 had initiated and were retained on ART, increasing coverage to 93%. A greater increase in ART coverage was achieved among men (40%) compared to women (29%). Of the 11,954 persons who had viral load (VL) test results, 11,687 (98%) were virally suppressed (HIV-1 RNA ≤400 copies/mL). Overall, 82% had documented VL suppression by study end. CONCLUSIONS: Knowledge of HIV-positive status and ART coverage increased towards 95-95 targets with universal testing, linkage interventions, and ART. The increases in HIV testing and ART use among men and youth were essential to reaching these targets. CLINICAL TRIAL NUMBER: NCT01965470.

Virtual axis finder: a new method to determine the two kinematic axes of rotation for the tibio-femoral joint.

The tibio-femoral joint has been mechanically approximated with two fixed kinematic axes of rotation, the longitudinal rotational (LR) axis in the tibia and the flexion-extension (FE) axis in the femur. The mechanical axis finder developed by Hollister et al. (1993, "The Axes of Rotation of the Knee," Clin. Orthop. Relat. Res., 290, pp. 259-268) identified the two fixed axes but the visual-based alignment introduced errors in the method. Therefore, the objectives were to develop and validate a new axis finding method to identify the LR and FE axes which improves on the error of the mechanical axis finder. The virtual axis finder retained the concepts of the mechanical axis finder but utilized a mathematical optimization to identify the axes. Thus, the axes are identified in a two-step process: First, the LR axis is identified from pure internal-external rotation of the tibia and the FE axis is identified after the LR axis is known. The validation used virtual simulations of 3D video-based motion analysis to create relative motion between the femur and tibia during pure internal-external rotation, and flexion-extension with coupled internal-external rotation. The simulations modeled tibio-femoral joint kinematics and incorporated 1 mm of random measurement error. The root mean squared errors (RMSEs) in identifying the position and orientation of the LR and FE axes with the virtual axis finder were 0.45 mm and 0.20 deg, and 0.11 mm and 0.20 deg, respectively. These errors are at least two times better in position and seven times better in orientation than those of the mechanical axis finder. Variables, which were considered a potential source of variation between joints and/or measurement systems, were tested for their sensitivity to the RMSE of identifying the axes. Changes in either the position or orientation of a rotational axis resulted in high sensitivity to translational RMSE (6.8 mm of RMSE per mm of translation) and rotational RMSE (1.38 deg of RMSE per degree of rotation), respectively. Notwithstanding these high sensitivities, corresponding errors can be reduced by segmenting the range of motion into regions where changes in either position or orientation are small. The virtual axis finder successfully increased the accuracy of the mechanical axis finder when the axes of motion are fixed with respect to the bones, but must be used judiciously in applications which do not have fixed axes of rotation.

Rapid antiretroviral therapy initiation in the Botswana Combination Prevention Project: a quasi-experimental before and after study.

BACKGROUND: Ensuring that individuals who are living with HIV rapidly initiate antiretroviral therapy (ART) is an essential step in meeting the 90-90-90 targets. We evaluated the feasibility and outcomes of rapid ART initiation in the Botswana Combination Prevention Project (BCPP). We aimed to establish whether simplified ART initiation with the offer of same-day treatment could increase uptake and reduce time from clinic linkage to treatment initiation, while maintaining rates of retention in care and viral suppression. METHODS: We did a quasi-experimental before and after study with use of data from the BCPP. The BCPP was a community-randomised HIV-prevention trial done in 30 communities across Botswana from Oct 1, 2013, to June 30, 2018. Participants in the 15 intervention clusters, who were HIV-positive and not already taking ART were offered universal HIV-treatment and same-day ART with a dolutegravir-based regimen at first clinic visit. This rapid ART intervention was implemented mid-way through the trial on June 1, 2016, enabling us to determine the effect of rapid ART guidelines on time to ART initiation and rates of retention in care and viral suppression at 1 year in the BCPP intervention group. FINDINGS: We assessed 1717 adults linked to study clinics before rapid ART introduction and 800 after rapid ART introduction. During the rapid ART period, 457 (57·1%, 95% CI 53·7-60·6) individuals initiated ART within 1 day of linkage, 589 (73·7%, 70·6-76·7) of 799 within 1 week, 678 (84·9%, 82·4-87·3) of 799 within 1 month, and 744 (93·5%, 91·6-95·1) of 796 within 1 year. Before the introduction of rapid ART, 163 (9·5%, 95% CI 8·2-11·0) individuals initiated ART within 1 day of linkage, 276 (16·1%, 14·4-17·9) within 1 week, 839 (48·9%, 46·5-51·3) within 1 month, and 1532 (89·2%, 87·7-90·6) within 1 year. 1 year after ART initiation, 1472 (90·5%, 87·4-92·8) of 1627 individuals who linked in the standard ART period were in care and had a viral load of less than 400 copies per mL, compared with 578 (91·6%, 88·1-94·1) of 631 in the rapid ART period (risk ratio 1·01, 95% CI 0·92-1·11). INTERPRETATION: Our findings provide support for the WHO recommendations for rapid ART initiation, and add to the accumulating evidence showing the feasibility, acceptability, and safety of rapid ART initiation in low-income and middle-income country settings. FUNDING: US President's Emergency Plan for AIDS Relief.

Self-reported risky sexual practices among adolescents and young adults in Botswana.

BACKGROUND: Adolescents and young adults account for more than one-third of incident Human Immunodeficiency Virus (HIV) infections globally. Understanding sexual practices of this high-risk group is critical in designing HIV targeted prevention programming. OBJECTIVES: To describe self-reported risky sexual practices of adolescents and young adults aged 16-24 years from 30 Botswana communities. METHODS: Cross-sectional, self-reported age at sexual debut; number of sexual partners; condom and alcohol use during sex; intergenerational sex; and transactional sex data were collected. Modified Poisson estimating equations were used to obtain univariate and multivariate-adjusted prevalence ratios (PR) and 95% confidence intervals (CI) comparing engagement in different sexual practices according to gender, accounting for the clustered design of the study. RESULTS: Among the 3380 participants, 2311 reported being sexually active with more females reporting being sexually active compared to males (65% vs. 35%, respectively; p < 0.0001). In univariate analyses, female participants were more likely to report inconsistent condom use (PR 1.61; 95% CI 1.44-1.80), intergenerational sex (PR 9.00; 95% CI 5.84-13.88) and transactional sex (PR 3.46; 95% CI 2.07-5.77) than males, yet less likely to report engaging in sex before age 15 years (PR 0.59; 95% CI: 0.41-0.85), using alcohol around the time of intercourse (PR: 0.59; 95% CI 0.45-0.76) or having ≥ two partners in the last 12 months (PR 0.65; 95% CI 0.57-0.74). CONCLUSIONS: Self-reported risky sexual practices of adolescents and young adults in Botswana differed significantly between males and females. Gender-specific risky sexual practices highlight the importance of developing tailored HIV prevention programming.

Increasing knowledge of HIV status in a country with high HIV testing coverage: Results from the Botswana Combination Prevention Project.

INTRODUCTION: Achieving widespread knowledge of HIV-positive status is a crucial step to reaching universal ART coverage, population level viral suppression, and ultimately epidemic control. We implemented a multi-modality HIV testing approach to identify 90% or greater of HIV-positive persons in the Botswana Combination Prevention Project (BCPP) intervention communities. METHODS: BCPP is a cluster-randomized trial designed to evaluate the impact of combination prevention interventions on HIV incidence in 30 communities in Botswana. Community case finding and HIV testing that included home and targeted mobile testing were implemented in the 15 intervention communities. We described processes for identifying HIV-positive persons, uptake of HIV testing by age, gender and venue, characteristics of persons newly diagnosed through BCPP, and coverage of knowledge of status reached at the end of study. RESULTS: Of the 61,655 eligible adults assessed in home or mobile settings, 13,328 HIV-positive individuals, or 93% of the estimated 14,270 positive people in the communities were identified through BCPP. Knowledge of status increased by 25% over the course of the study with the greatest increases seen among men (37%) as compared to women (19%) and among youth aged 16-24 (77%) as compared to older age groups (21%). Although more men were tested through mobile than through home-based testing, higher rates of newly diagnosed HIV-positive men were found through home than mobile testing. CONCLUSIONS: Even when HIV testing coverage is high, additional gains can be made using a multi-modality HIV testing strategy to reach different sub-populations who are being missed by non-targeted program activities. Men and youth can be reached and will engage in community testing when services are brought to places they access routinely.

Transfemoral amputee intact limb loading and compensatory gait mechanics during down slope ambulation and the effect of prosthetic knee mechanisms.

BACKGROUND: Intact limb knee osteoarthritis is a prevalent secondary disability in transfemoral amputees. Walking down a ramp may increase this risk due to excessive limb loading. We sought to determine whether intact limb loading differed between transfemoral amputees and controls during down slope ambulation, and the compensatory strategies transfemoral amputees used to modify intact limb loading. Secondarily, we sought to determine the effect of prosthetic knee type. METHODS: Five unilateral transfemoral amputees and five non-amputee controls walked down a ramp and the following outcome measures were compared between amputees and controls and across prosthetic knee type (C-leg versus Power Knee): step length, walking speed, leading limb ground reaction forces, and trailing and leading limb ankle and knee energy absorption. Linear mixed effects regression was used to test for association between gait variables and limb. FINDINGS: There were no significant differences in intact limb loading between amputees and controls or between prosthetic knee types. Transfemoral amputees walked slower (C-leg - control = -0.29 m/s; P = 0.008, Power Knee - control = -0.38 m/s; P < 0.001) with a shorter intact limb step length (C-leg - control = -0.12 m/s; P < 0.001, Power Knee - control = -0.16 m/s; P < 0.001). The prosthetic trailing limb ankle absorbed less energy throughout stance than the trailing limb in controls (C-leg-control = -0.22 J/kg; P < 0.001, Power Knee - control = -0.22 J/kg; P < 0.001). INTERPRETATION: Intact limb loading in transfemoral amputees is equivalent to controls during down ramp ambulation, in spite of reduced prosthetic trailing limb energy absorption. The primary compensatory strategies include a reduced ambulation speed and intact limb step length, which reduces center of mass velocity at heel contact.