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BACKGROUND:Uptake of antiretroviral treatment (ART) is expanding rapidly in low- and middle-income countries (LMIC). Monitoring of virological suppression is recommended at 6 months of treatment and annually thereafter. In case of confirmed virological failure, a switch to second-line ART is indicated. There is a paucity of data on virological suppression and clinical management of patients experiencing viremia in clinical practice in LMIC. We report a large-scale multicenter assessment of virological suppression over time and management of viremia under programmatic conditions. METHODS AND FINDINGS:Linked medical record and laboratory source data from adult patients on first-line ART at 52 South African centers between 1 January 2007 and 1 May 2018 were studied. Virological suppression, switch to second-line ART, death, and loss to follow-up were analyzed. Multistate models and Cox proportional hazard models were used to assess suppression over time and predictors of treatment outcomes. A total of 104,719 patients were included. Patients were predominantly female (67.6%). Median age was 35.7 years (interquartile range [IQR]: 29.9-43.0). In on-treatment analysis, suppression below 1,000 copies/mL was 89.0% at month 12 and 90.4% at month 72. Suppression below 50 copies/mL was 73.1% at month 12 and 77.5% at month 72. Intention-to-treat suppression was 75.0% and 64.3% below 1,000 and 50 copies/mL at month 72, respectively. Viremia occurred in 19.8% (20,766/104,719) of patients during a median follow-up of 152 (IQR: 61-265) weeks. Being male and below 35 years of age and having a CD4 count below 200 cells/μL prior to start of ART were risk factors for viremia. After detection of viremia, confirmatory testing took 29 weeks (IQR: 16-54). Viral resuppression to below 1,000 copies/mL without switch of ART occurred frequently (45.6%; 6,030/13,210) but was associated with renewed viral rebound and switch. Of patients with confirmed failure who remained in care, only 41.5% (1,872/4,510) were switched. The median time to switch was 68 weeks (IQR: 35-127), resulting in 12,325 person-years spent with a viral load above 1,000 copies/mL. Limitations of this study include potential missing data, which is in part addressed by the use of cross-matched laboratory source data, and the possibility of unmeasured confounding. CONCLUSIONS:In this study, 90% virological suppression below the threshold of 1,000 copies/mL was observed in on-treatment analysis. However, this target was not met at the 50-copies/mL threshold or in intention-to-treat analysis. Clinical management in response to viremia was profoundly delayed, prolonging the duration of viremia and potential for transmission. Diagnostic tools to establish the cause of viremia are urgently needed to accelerate clinical decision-making.

BACKGROUND: Uptake of antiretroviral treatment (ART) is expanding rapidly in low- and middle-income countries (LMIC). Monitoring of virological suppression is recommended at 6 months of treatment and annually thereafter. In case of confirmed virological failure, a switch to second-line ART is indicated. There is a paucity of data on virological suppression and clinical management of patients experiencing viremia in clinical practice in LMIC. We report a large-scale multicenter assessment of virological suppression over time and management of viremia under programmatic conditions. METHODS AND FINDINGS: Linked medical record and laboratory source data from adult patients on first-line ART at 52 South African centers between 1 January 2007 and 1 May 2018 were studied. Virological suppression, switch to second-line ART, death, and loss to follow-up were analyzed. Multistate models and Cox proportional hazard models were used to assess suppression over time and predictors of treatment outcomes. A total of 104,719 patients were included. Patients were predominantly female (67.6%). Median age was 35.7 years (interquartile range [IQR]: 29.9-43.0). In on-treatment analysis, suppression below 1,000 copies/mL was 89.0% at month 12 and 90.4% at month 72. Suppression below 50 copies/mL was 73.1% at month 12 and 77.5% at month 72. Intention-to-treat suppression was 75.0% and 64.3% below 1,000 and 50 copies/mL at month 72, respectively. Viremia occurred in 19.8% (20,766/104,719) of patients during a median follow-up of 152 (IQR: 61-265) weeks. Being male and below 35 years of age and having a CD4 count below 200 cells/μL prior to start of ART were risk factors for viremia. After detection of viremia, confirmatory testing took 29 weeks (IQR: 16-54). Viral resuppression to below 1,000 copies/mL without switch of ART occurred frequently (45.6%; 6,030/13,210) but was associated with renewed viral rebound and switch. Of patients with confirmed failure who remained in care, only 41.5% (1,872/4,510) were switched. The median time to switch was 68 weeks (IQR: 35-127), resulting in 12,325 person-years spent with a viral load above 1,000 copies/mL. Limitations of this study include potential missing data, which is in part addressed by the use of cross-matched laboratory source data, and the possibility of unmeasured confounding. CONCLUSIONS: In this study, 90% virological suppression below the threshold of 1,000 copies/mL was observed in on-treatment analysis. However, this target was not met at the 50-copies/mL threshold or in intention-to-treat analysis. Clinical management in response to viremia was profoundly delayed, prolonging the duration of viremia and potential for transmission. Diagnostic tools to establish the cause of viremia are urgently needed to accelerate clinical decision-making.

BACKGROUND:Uptake of antiretroviral treatment (ART) is expanding rapidly in low- and middle-income countries (LMIC). Monitoring of virological suppression is recommended at 6 months of treatment and annually thereafter. In case of confirmed virological failure, a switch to second-line ART is indicated. There is a paucity of data on virological suppression and clinical management of patients experiencing viremia in clinical practice in LMIC. We report a large-scale multicenter assessment of virological suppression over time and management of viremia under programmatic conditions. METHODS AND FINDINGS:Linked medical record and laboratory source data from adult patients on first-line ART at 52 South African centers between 1 January 2007 and 1 May 2018 were studied. Virological suppression, switch to second-line ART, death, and loss to follow-up were analyzed. Multistate models and Cox proportional hazard models were used to assess suppression over time and predictors of treatment outcomes. A total of 104,719 patients were included. Patients were predominantly female (67.6%). Median age was 35.7 years (interquartile range [IQR]: 29.9-43.0). In on-treatment analysis, suppression below 1,000 copies/mL was 89.0% at month 12 and 90.4% at month 72. Suppression below 50 copies/mL was 73.1% at month 12 and 77.5% at month 72. Intention-to-treat suppression was 75.0% and 64.3% below 1,000 and 50 copies/mL at month 72, respectively. Viremia occurred in 19.8% (20,766/104,719) of patients during a median follow-up of 152 (IQR: 61-265) weeks. Being male and below 35 years of age and having a CD4 count below 200 cells/μL prior to start of ART were risk factors for viremia. After detection of viremia, confirmatory testing took 29 weeks (IQR: 16-54). Viral resuppression to below 1,000 copies/mL without switch of ART occurred frequently (45.6%; 6,030/13,210) but was associated with renewed viral rebound and switch. Of patients with confirmed failure who remained in care, only 41.5% (1,872/4,510) were switched. The median time to switch was 68 weeks (IQR: 35-127), resulting in 12,325 person-years spent with a viral load above 1,000 copies/mL. Limitations of this study include potential missing data, which is in part addressed by the use of cross-matched laboratory source data, and the possibility of unmeasured confounding. CONCLUSIONS:In this study, 90% virological suppression below the threshold of 1,000 copies/mL was observed in on-treatment analysis. However, this target was not met at the 50-copies/mL threshold or in intention-to-treat analysis. Clinical management in response to viremia was profoundly delayed, prolonging the duration of viremia and potential for transmission. Diagnostic tools to establish the cause of viremia are urgently needed to accelerate clinical decision-making.

The high field superconducting magnets required for ongoing and planned upgrades to the Large Hadron Collider (LHC) will be wound with Nb3Sn Rutherford cables for which reason studies of Nb3Sn strand, cable, and magnet properties will continue to be needed. Of particular importance is field quality. The amplitudes of multipoles in the bore fields of dipole and quadrupole magnets, induced by ramp-rate-dependent coupling currents, are under the control of the interstrand contact resistances-crossing-strand, $R-{c}$, adjacent strand, $R-{a}$ , or a combination of them, $R-{{\text{eff}}}$. Although two decades ago it was agreed that for the LHC $R-{c}$ should be in the range 10-30 μ, more recent measurements of LHC quadrupoles have revealed $R-{c}$ values ranging from 95 to 230 μ. This paper discusses ways in which these values can be achieved. In a heavily compacted cable $R-{{\text{eff}}}$ can be tuned to some predictable value by varying the width of an included stainless steel (effectively 'insulating') core. But cables are no longer heavily compacted with the result that the crossing strands of the impregnated cable are separated by a thick epoxy layer that behaves like an insulating core. If a stainless steel core is actually present, $R-{{\text{eff}}}$ must be independent of core width. Since there is no guarantee that a fixed predetermined amount of interlayer separation could be reproduced from winding to winding it would be advisable to include a full width core.

The high field superconducting magnets required for ongoing and planned upgrades to the Large Hadron Collider (LHC) will be wound with Nb3Sn Rutherford cables for which reason studies of Nb3Sn strand, cable, and magnet properties will continue to be needed. Of particular importance is field quality. The amplitudes of multipoles in the bore fields of dipole and quadrupole magnets, induced by ramp-rate-dependent coupling currents, are under the control of the interstrand contact resistances-crossing-strand, $R-{c}$, adjacent strand, $R-{a}$ , or a combination of them, $R-{{\text{eff}}}$. Although two decades ago it was agreed that for the LHC $R-{c}$ should be in the range 10-30 μ, more recent measurements of LHC quadrupoles have revealed $R-{c}$ values ranging from 95 to 230 μ. This paper discusses ways in which these values can be achieved. In a heavily compacted cable $R-{{\text{eff}}}$ can be tuned to some predictable value by varying the width of an included stainless steel (effectively 'insulating') core. But cables are no longer heavily compacted with the result that the crossing strands of the impregnated cable are separated by a thick epoxy layer that behaves like an insulating core. If a stainless steel core is actually present, $R-{{\text{eff}}}$ must be independent of core width. Since there is no guarantee that a fixed predetermined amount of interlayer separation could be reproduced from winding to winding it would be advisable to include a full width core.

The magnetizations of eight high-gradient quadrupole cables designated HQ and QXF and a pair of strands, identical in architecture but with different effective strand diameters extracted from an HQ and a related QXF cable, were measured. In the service of field quality assessment, the cable magnetizations and losses were measured by pickup coil magnetometry at 4.2 K in face-on fields, B m , of ± 400 mT at frequencies, f, of up to 60 mHz. Based on the coupling component of loss, Q coup , the coupling magnetization M coup = Q coup /4B m was derived for a ramp rate of 7.5 mT/s. Persistent current (shielding) magnetization and loss (M sh and Q h,strand ) were measured on short pieces of extracted strand by vibrating sample magnetometry at 4.2 K. Unpenetrated M-B loops to ±400 mT and fully penetrated loops to ±14 T were obtained. M coup can be easily controlled and reduced to relatively small values by introducing cores and adjusting the preparation conditions. But in low fields near injection Nb3Sn's high J c and correspondingly high M sh,cable may call for magnetic compensation to preserve field quality. The suitably adjusted cable and strand fully penetrated M-B loops were in reasonable accord leading to the conclusion that strand magnetization is a useful measure of cable magnetization, and that when suitably manipulated can provide input to magnet field error calculations.

The magnetizations of eight high-gradient quadrupole cables designated HQ and QXF and a pair of strands, identical in architecture but with different effective strand diameters extracted from an HQ and a related QXF cable, were measured. In the service of field quality assessment, the cable magnetizations and losses were measured by pickup coil magnetometry at 4.2 K in face-on fields, B m , of ± 400 mT at frequencies, f, of up to 60 mHz. Based on the coupling component of loss, Q coup , the coupling magnetization M coup = Q coup /4B m was derived for a ramp rate of 7.5 mT/s. Persistent current (shielding) magnetization and loss (M sh and Q h,strand ) were measured on short pieces of extracted strand by vibrating sample magnetometry at 4.2 K. Unpenetrated M-B loops to ±400 mT and fully penetrated loops to ±14 T were obtained. M coup can be easily controlled and reduced to relatively small values by introducing cores and adjusting the preparation conditions. But in low fields near injection Nb3Sn's high J c and correspondingly high M sh,cable may call for magnetic compensation to preserve field quality. The suitably adjusted cable and strand fully penetrated M-B loops were in reasonable accord leading to the conclusion that strand magnetization is a useful measure of cable magnetization, and that when suitably manipulated can provide input to magnet field error calculations.

Calorimetric measurement of coupling loss versus frequency has been measured on two sets of cored and uncored large Hadron Collider Accelerator Research Program high gradient quadrupole Nb3Sn Rutherford cables. Studied are the responses of the resulting interstrand contact resistances (ICR) to variation of stainless-steel (SS) core width and position and to variation of reaction-heat-treatment (RHT) condition. One pair of cables (an early HQ-series type) with and without core had received RHT under 20-MPa uniaxial face-on pressure. Another set of cables (recent QXF type) furnished with SS cores of various widths had received RHT under ambient pressure. The results were displayed as cable-cross-sectional micrographs and plots of ICR versus percent core coverage (W). The HQ cables were tightly compacted and produced results consistent with a previously expected continuous ICR versus W variation. On the other hand, the QXF cables were uncompacted such that their upper and lower layers were separated by what is referred to as a full-width 'pseudocore;' as a result, their ICRs were independent of the widths of the SS cores. Compaction versus noncompaction is discussed and future research directions are suggested.

Calorimetric measurement of coupling loss versus frequency has been measured on two sets of cored and uncored large Hadron Collider Accelerator Research Program high gradient quadrupole Nb3Sn Rutherford cables. Studied are the responses of the resulting interstrand contact resistances (ICR) to variation of stainless-steel (SS) core width and position and to variation of reaction-heat-treatment (RHT) condition. One pair of cables (an early HQ-series type) with and without core had received RHT under 20-MPa uniaxial face-on pressure. Another set of cables (recent QXF type) furnished with SS cores of various widths had received RHT under ambient pressure. The results were displayed as cable-cross-sectional micrographs and plots of ICR versus percent core coverage (W). The HQ cables were tightly compacted and produced results consistent with a previously expected continuous ICR versus W variation. On the other hand, the QXF cables were uncompacted such that their upper and lower layers were separated by what is referred to as a full-width 'pseudocore;' as a result, their ICRs were independent of the widths of the SS cores. Compaction versus noncompaction is discussed and future research directions are suggested.

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy.

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy.

The "Berlin patient" is the first patient cured of HIV-1 infection after allogeneic transplantation with nonfunctional CCR5 coreceptor stem cells. We demonstrate that CXCR4-predicted minority viruses present prior to transplantation were unable to rebound after transplantation due to their dependence on CCR5 for replication and high genetic barrier toward CXCR4 usage.

Background: Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing ri