HIV post-treatment controllers have distinct immunological and virological features.

HIV post-treatment controllers (PTCs) are rare individuals who maintain low levels of viremia after stopping antiretroviral therapy (ART). Understanding the mechanisms of HIV post-treatment control will inform development of strategies aiming at achieving HIV functional cure. In this study, we evaluated 22 PTCs from 8 AIDS Clinical Trials Group (ACTG) analytical treatment interruption (ATI) studies who maintained viral loads ≤400 copies/mL for ≥24 wk. There were no significant differences in demographics or frequency of protective and susceptible human leukocyte antigen (HLA) alleles between PTCs and post-treatment noncontrollers (NCs, n = 37). Unlike NCs, PTCs demonstrated a stable HIV reservoir measured by cell-associated RNA (CA-RNA) and intact proviral DNA assay (IPDA) during analytical treatment interruption (ATI). Immunologically, PTCs demonstrated significantly lower CD4+ and CD8+ T cell activation, lower CD4+ T cell exhaustion, and more robust Gag-specific CD4+ T cell responses and natural killer (NK) cell responses. Sparse partial least squares discriminant analysis (sPLS-DA) identified a set of features enriched in PTCs, including a higher CD4+ T cell% and CD4+/CD8+ ratio, more functional NK cells, and a lower CD4+ T cell exhaustion level. These results provide insights into the key viral reservoir features and immunological profiles for HIV PTCs and have implications for future studies evaluating interventions to achieve an HIV functional cure.

Transcriptomic Signatures of Human Immunodeficiency Virus Post-Treatment Control.

Posttreatment controllers (PTCs) are rare HIV-infected individuals who can limit viral rebound after antiretroviral therapy interruption (ATI), but the mechanisms of this remain unclear. To investigate these mechanisms, we quantified various HIV RNA transcripts (via reverse transcription droplet digital PCR [RT-ddPCR]) and cellular transcriptomes (via RNA-seq) in blood cells from PTCs and noncontrollers (NCs) before and two time points after ATI. HIV transcription initiation did not significantly increase after ATI in PTCs or in NCs, whereas completed HIV transcripts increased at early ATI in both groups and multiply-spliced HIV transcripts increased only in NCs. Compared to NCs, PTCs showed lower levels of HIV DNA, more cell-associated HIV transcripts per total RNA at all times, no increase in multiply-spliced HIV RNA at early or late ATI, and a reduction in the ratio of completed/elongated HIV RNA after early ATI. NCs expressed higher levels of the IL-7 pathway before ATI and expressed higher levels of multiple cytokine, inflammation, HIV transcription, and cell death pathways after ATI. Compared to the baseline, the NCs upregulated interferon and cytokine (especially TNF) pathways during early and late ATI, whereas PTCs upregulated interferon and p53 pathways only at early ATI and downregulated gene translation during early and late ATI. In NCs, viral rebound after ATI is associated with increases in HIV transcriptional completion and splicing, rather than initiation. Differences in HIV and cellular transcription may contribute to posttreatment control, including an early limitation of spliced HIV RNA, a delayed reduction in completed HIV transcripts, and the differential expression of the IL-7, p53, and TNF pathways. IMPORTANCE The findings presented here provide new insights into how HIV and cellular gene expression change after stopping ART in both noncontrollers and posttreatment controllers. Posttreatment control is associated with an early ability to limit increases in multiply-spliced HIV RNA, a delayed (and presumably immune-mediated) ability to reverse an initial rise in processive/completed HIV transcripts, and multiple differences in cellular gene expression pathways. These differences may represent correlates or mechanisms of posttreatment control and may provide insight into the development and/or monitoring of therapeutic strategies that are aimed at a functional HIV cure.

Sexual Practice Changes Post-HIV Diagnosis Among Men Who Have Sex with Men in the United States: A Systematic Review and Meta-analysis.

Men who have sex with men (MSM) often change sexual behaviors following HIV diagnosis. This systematic review examined such changes, including sero-adaptive behaviors (i.e., deliberate safer-sex practices to reduce transmission risk) to better understand the magnitude of their association with HIV diagnosis. We searched four databases (1996-2017) and reviewed references from other systematic reviews. We included studies conducted in the United States that compared sexual behavior among HIV-infected "aware" versus "unaware" MSM. We meta-analytically pooled RRs and associated 95% confidence intervals (CI) using random-effects models, and assessed risk of bias and evidence quality. Twenty studies reported k = 131 effect sizes on sexual practices outcomes, most of which reported changes in unprotected sex (k = 85), and on sex with at-risk partners (k = 76); 11 reported sero-adaptive behaviors. Unprotected anal intercourse with an HIV-uninfected/unknown-status partner was less likely among aware MSM (insertive position: k = 2, RR 0.26, 95% CI 0.17, 0.41; receptive position: k = 2, RR 0.53, 95% CI 0.37, 0.77). Risk of not always serosorting among aware MSM (k = 3) was RR = 0.92 (0.83, 1.02). Existing evidence, although low-quality, suggests that HIV-infected MSM tend to adopt safer sexual practices once aware of their diagnosis. Variation in reporting of outcomes limits their comparability. Sero-adaptive behavior data are sparse.

Change in Condom Use in Populations Newly Aware of HIV Diagnosis in the United States and Canada: A Systematic Review and Meta-Analysis.

HIV-infected individuals "aware" of their infection are more likely to use condoms, compared to HIV-infected "unaware" persons. To quantify this likelihood, we undertook a systematic review and meta-analysis of U.S. and Canadian studies. Twenty-one eligible studies included men who have sex with men (MSM; k = 15), persons who inject drugs (PWID; k = 2), and mixed populations of high-risk heterosexuals (HRH; k = 4). Risk ratios (RR) of "not always using condoms" with partners of any serostatus were lower among aware MSM (RR 0.44 [not significant]), PWID (RR 0.70) and HRH (RR 0.27); and, in aware MSM, with partners of HIV-uninfected or unknown status (RR 0.46). Aware individuals had lower "condomless sex likelihood" with HIV-uninfected or unknown status partners (MSM: RR 0.58; male PWID: RR 0.44; female PWID: RR 0.65; HRH: RR 0.35) and with partners of any serostatus (MSM only, RR 0.72). The association diminished over time. High risk of bias compromised evidence quality.

Health care utilization and HIV clinical outcomes among newly enrolled patients following Affordable Care Act implementation in a California integrated health system: a longitudinal study.

BACKGROUND: The Affordable Care Act (ACA) has increased insurance coverage for people with HIV (PWH) in the United States. To inform health policy, it is useful to investigate how enrollment through ACA Exchanges, deductible levels, and demographic factors are associated with health care utilization and HIV clinical outcomes among individuals newly enrolled in insurance coverage following implementation of the ACA. METHODS: Among PWH newly enrolled in an integrated health care system (Kaiser Permanente Northern California) in 2014 (N = 880), we examined use of health care and modeled associations between enrollment mechanisms (enrolled in a Qualified Health Plan through the California Exchange vs. other sources), deductibles (none, $1-$999 and > = $1000), receipt of benefits from the California AIDS Drug Assistance Program (ADAP), demographic factors, and three-year patterns of health service utilization (primary care, psychiatry, substance treatment, emergency, inpatient) and HIV outcomes (CD4 counts; viral suppression at HIV RNA < 75 copies/mL). RESULTS: Health care use was greatest immediately after enrollment and decreased over 3 years. Those with high deductibles were less likely to use primary care (OR = 0.64, 95% CI = 0.49-0.84, p < 0.01) or psychiatry OR = 0.59, 95% CI = 0.37, 0.94, p = 0.03) than those with no deductible. Enrollment via the Exchange was associated with fewer psychiatry visits (rate ratio [RR] = 0.40, 95% CI = 0.18-0.86; p = 0.02), but ADAP was associated with more psychiatry visits (RR = 2.22, 95% CI = 1.24-4.71; p = 0.01). Those with high deductibles were less likely to have viral suppression (OR = 0.65, 95% CI = 0.42-1.00; p = 0.05), but ADAP enrollment was associated with viral suppression (OR = 2.20, 95% CI = 1.32-3.66, p < 0.01). Black (OR = 0.35, 95% CI = 0.21-0.58, p < 0.01) and Hispanic (OR = 0.50, 95% CI = 0.29-0.85, p = 0.01) PWH were less likely to be virally suppressed. CONCLUSIONS: In this sample of PWH newly enrolled in an integrated health care system in California, findings suggest that enrollment via the Exchange and higher deductibles were negatively associated with some aspects of service utilization, high deductibles were associated with worse HIV outcomes, but support from ADAP appeared to help patients achieve viral suppression. Race/ethnic disparities remain important to address even among those with access to insurance coverage.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2020 Recommendations of the International Antiviral Society-USA Panel.

Importance: Data on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices. Objective: To evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV. Evidence Review: New evidence was collected since the previous International Antiviral (formerly AIDS) Society-USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations. Findings: From 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic. Conclusion and Relevance: Advances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.

Effect of Short-Term Antiretroviral Therapy Interruption on Levels of Integrated HIV DNA.

Analytic treatment interruption (ATI) studies are required to evaluate strategies aimed at achieving ART-free HIV remission, but the impact of ATI on the viral reservoir remains unclear. We validated a DNA size selection-based assay for measuring levels of integrated HIV DNA and applied it to assess the effects of short-term ATI on the HIV reservoir. Samples from participants from four AIDS Clinical Trials Group ATI studies were assayed for integrated HIV DNA levels. Cryopreserved peripheral blood mononuclear cells (PBMCs) were obtained for 12 participants with available samples pre-ATI and approximately 6 months after ART resumption. Four participants also had samples available during the ATI. The median duration of ATI was 12 weeks. Validation of the HIV integrated DNA size-exclusion (HIDE) assay was performed using samples spiked with unintegrated HIV DNA, HIV-infected cell lines, and participant PBMCs. The HIDE assay eliminated 99% of unintegrated HIV DNA species and strongly correlated with the established Alu-gag assay. For the majority of individuals, integrated DNA levels increased during ATI and subsequently declined upon ART resumption. There was no significant difference in the levels of integrated HIV DNA between the pre- and post-ATI time points, with a median ratio of post- to pre-ATI HIV DNA levels of 0.95. Using a new integrated HIV DNA assay, we found minimal change in the levels of integrated HIV DNA in participants who underwent an ATI, followed by 6 months of ART. This suggests that short-term ATI can be conducted without a significant impact on the levels of integrated proviral DNA in the peripheral blood.IMPORTANCE Interventions aimed at achieving sustained antiretroviral therapy (ART)-free HIV remission require treatment interruption trials to assess their efficacy. However, these trials are accompanied by safety concerns related to the expansion of the viral reservoir. We validated an assay that uses an automated DNA size-selection platform for quantifying levels of integrated HIV DNA and is less sample- and labor-intensive than current assays. Using stored samples from AIDS Clinical Trials Group studies, we found that short-term ART discontinuation had minimal impact on integrated HIV DNA levels after ART resumption, providing reassurance about the reservoir effects of short-term treatment interruption trials.

Interventions to Reduce Unhealthy Alcohol Use among Primary Care Patients with HIV: the Health and Motivation Randomized Clinical Trial.

BACKGROUND: Unhealthy alcohol use has adverse effects on HIV treatment. Screening, brief intervention, and referral to treatment (SBIRT) has some evidence of efficacy but may not be sufficient for those with low motivation or comorbid substance use. OBJECTIVE: To examine the effectiveness of motivational interviewing (MI) and emailed feedback (EF) among primary care HIV-positive patients, compared with treatment as usual care (UC) only, which included SBIRT. DESIGN: Randomized clinical trial. PARTICIPANTS: Six hundred fourteen adult HIV-positive patients in Kaiser Permanente Northern California who reported prior-year unhealthy alcohol use. INTERVENTION: Participants were randomized to either three sessions of MI (one in person and two by phone), information regarding alcohol risks via EF through a patient portal, or UC alone. MI and EF participants who reported unhealthy alcohol use at 6 months were offered additional MI and EF treatment, respectively. MAIN MEASURES: Participant-reported unhealthy alcohol use (defined as ≥ 4/≥ 5 drinks per day for women/men), alcohol problems at 12 months, based on blinded telephone interviews. Secondary outcomes included drug use and antiretroviral (ART) adherence. KEY RESULTS: At 12 months, there were no overall group differences, but in all three arms, there were declines in unhealthy alcohol use and alcohol-related problems (p < 0.001). Participants reporting low motivation to reduce drinking at baseline were less likely to report unhealthy alcohol use if they received MI vs. EF and UC (p = 0.013). At 6 months, reported illegal drug use/misuse of prescription drugs other than marijuana was lower in the MI arm than EF or UC (p = 0.012). There were no differences in ART adherence between groups. CONCLUSIONS: In a randomized trial of HIV-positive patients using two behavioral interventions compared with SBIRT alone, participants in all three conditions reduced unhealthy alcohol use. MI may provide added benefit for patients with low motivation or who report illegal drug use/misuse of prescription drugs. TRIAL REGISTRATION: NCT01671501 ( ClinicalTrials.gov ).

The Control of HIV After Antiretroviral Medication Pause (CHAMP) Study: Posttreatment Controllers Identified From 14 Clinical Studies.

Background: HIV posttreatment controllers are rare individuals who start antiretroviral therapy (ART), but maintain HIV suppression after treatment interruption. The frequency of posttreatment control and posttreatment interruption viral dynamics have not been well characterized. Methods: Posttreatment controllers were identified from 14 studies and defined as individuals who underwent treatment interruption with viral loads ≤400 copies/mL at two-thirds or more of time points for ≥24 weeks. Viral load and CD4+ cell dynamics were compared between posttreatment controllers and noncontrollers. Results: Of the 67 posttreatment controllers identified, 38 initiated ART during early HIV infection. Posttreatment controllers were more frequently identified in those treated during early versus chronic infection (13% vs 4%, P < .001). In posttreatment controllers with weekly viral load monitoring, 45% had a peak posttreatment interruption viral load of ≥1000 copies/mL and 33% had a peak viral load ≥10000 copies/mL. Of posttreatment controllers, 55% maintained HIV control for 2 years, with approximately 20% maintaining control for ≥5 years. Conclusions: Posttreatment control was more commonly identified amongst early treated individuals, frequently characterized by early transient viral rebound and heterogeneous durability of HIV remission. These results may provide mechanistic insights and have implications for the design of trials aimed at achieving HIV remission.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2018 Recommendations of the International Antiviral Society-USA Panel.

Importance: Antiretroviral therapy (ART) is the cornerstone of prevention and management of HIV infection. Objective: To evaluate new data and treatments and incorporate this information into updated recommendations for initiating therapy, monitoring individuals starting therapy, changing regimens, and preventing HIV infection for individuals at risk. Evidence Review: New evidence collected since the International Antiviral Society-USA 2016 recommendations via monthly PubMed and EMBASE literature searches up to April 2018; data presented at peer-reviewed scientific conferences. A volunteer panel of experts in HIV research and patient care considered these data and updated previous recommendations. Findings: ART is recommended for virtually all HIV-infected individuals, as soon as possible after HIV diagnosis. Immediate initiation (eg, rapid start), if clinically appropriate, requires adequate staffing, specialized services, and careful selection of medical therapy. An integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is generally recommended for initial therapy, with unique patient circumstances (eg, concomitant diseases and conditions, potential for pregnancy, cost) guiding the treatment choice. CD4 cell count, HIV RNA level, genotype, and other laboratory tests for general health and co-infections are recommended at specified points before and during ART. If a regimen switch is indicated, treatment history, tolerability, adherence, and drug resistance history should first be assessed; 2 or 3 active drugs are recommended for a new regimen. HIV testing is recommended at least once for anyone who has ever been sexually active and more often for individuals at ongoing risk for infection. Preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine and appropriate monitoring is recommended for individuals at risk for HIV. Conclusions and Relevance: Advances in HIV prevention and treatment with antiretroviral drugs continue to improve clinical management and outcomes for individuals at risk for and living with HIV.

Crowdsourcing HIV Test Promotion Videos: A Noninferiority Randomized Controlled Trial in China.

BACKGROUND: Crowdsourcing, the process of shifting individual tasks to a large group, may enhance human immunodeficiency virus (HIV) testing interventions. We conducted a noninferiority, randomized controlled trial to compare first-time HIV testing rates among men who have sex with men (MSM) and transgender individuals who received a crowdsourced or a health marketing HIV test promotion video. METHODS: Seven hundred twenty-one MSM and transgender participants (≥16 years old, never before tested for HIV) were recruited through 3 Chinese MSM Web portals and randomly assigned to 1 of 2 videos. The crowdsourced video was developed using an open contest and formal transparent judging while the evidence-based health marketing video was designed by experts. Study objectives were to measure HIV test uptake within 3 weeks of watching either HIV test promotion video and cost per new HIV test and diagnosis. RESULTS: Overall, 624 of 721 (87%) participants from 31 provinces in 217 Chinese cities completed the study. HIV test uptake was similar between the crowdsourced arm (37% [114/307]) and the health marketing arm (35% [111/317]). The estimated difference between the interventions was 2.1% (95% confidence interval, -5.4% to 9.7%). Among those tested, 31% (69/225) reported a new HIV diagnosis. The crowdsourced intervention cost substantially less than the health marketing intervention per first-time HIV test (US$131 vs US$238 per person) and per new HIV diagnosis (US$415 vs US$799 per person). CONCLUSIONS: Our nationwide study demonstrates that crowdsourcing may be an effective tool for improving HIV testing messaging campaigns and could increase community engagement in health campaigns. CLINICAL TRIALS REGISTRATION: NCT02248558.

Facilitators of HCV treatment adherence among people who inject drugs: a systematic qualitative review and implications for scale up of direct acting antivirals.

BACKGROUND: While the public health benefits of new HCV treatments depend on treatment adherence, particularly among people who inject drugs (PWID), several social and medical factors can jeopardize treatment adherence. The aim of this study is to examine the qualitative literature on facilitators to HCV treatment adherence among PWID. METHODS: We searched six databases to identify qualitative research studies on HCV treatment adherence facilitators among PWID. Two reviewers independently extracted and analyzed data using PRISMA guidelines and the CASP tool to evaluate study quality. RESULTS: From ten studies representing data from 525 participants, three major themes emerged across studies: logistical facilitators within health systems enhanced HCV treatment adherence, positive social interactions between PWID and staff provided positive feedback during treatment, and HCV treatment may complicate the addiction recovery process. CONCLUSIONS: Although PWID face several barriers to adherence, we identified treatment adherence facilitators that could be incorporated into clinical practice.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society-USA Panel.

IMPORTANCE: New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. OBJECTIVE: To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. EVIDENCE REVIEW: A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. FINDINGS: Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure. CONCLUSIONS AND RELEVANCE: Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults.

Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel.

IMPORTANCE: New data and antiretroviral regimens expand treatment choices in resource-rich settings and warrant an update of recommendations to treat adults infected with human immunodeficiency virus (HIV). OBJECTIVE: To provide updated treatment recommendations for adults with HIV, emphasizing when to start treatment; what treatment to start; the use of laboratory monitoring tools; and managing treatment failure, switches, and simplification. DATA SOURCES, STUDY SELECTION, AND DATA SYNTHESIS: An International Antiviral Society-USA panel of experts in HIV research and patient care considered previous data and reviewed new data since the 2012 update with literature searches in PubMed and EMBASE through June 2014. Recommendations and ratings were based on the quality of evidence and consensus. RESULTS: Antiretroviral therapy is recommended for all adults with HIV infection. Evidence for benefits of treatment and quality of available data increase at lower CD4 cell counts. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (NRTIs; abacavir/lamivudine or tenofovir disoproxil fumarate/emtricitabine) and a third single or boosted drug, which should be an integrase strand transfer inhibitor (dolutegravir, elvitegravir, or raltegravir), a nonnucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine) or a boosted protease inhibitor (darunavir or atazanavir). Alternative regimens are available. Boosted protease inhibitor monotherapy is generally not recommended, but NRTI-sparing approaches may be considered. New guidance for optimal timing of monitoring of laboratory parameters is provided. Suspected treatment failure warrants rapid confirmation, performance of resistance testing while the patient is receiving the failing regimen, and evaluation of reasons for failure before consideration of switching therapy. Regimen switches for adverse effects, convenience, or to reduce costs should not jeopardize antiretroviral potency. CONCLUSIONS AND RELEVANCE: After confirmed diagnosis of HIV infection, antiretroviral therapy should be initiated in all individuals who are willing and ready to start treatment. Regimens should be selected or changed based on resistance test results with consideration of dosing frequency, pill burden, adverse toxic effect profiles, comorbidities, and drug interactions.

A roadmap to establishing global oncology as a priority initiative within a National Cancer Institute-designated cancer center.

As the burden of cancers impacting low- and middle-income countries is projected to increase, formation of strategic partnerships between institutions in high-income countries and low- and middle-income country institutions may serve to accelerate cancer research, clinical care, and training. As the US National Cancer Institute and its Center for Global Health continue to encourage cancer centers to join its global mission, academic cancer centers in the United States have increased their global activities. In 2015, the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, responded to the call for international partnership in addressing the global cancer burden through the establishment of the Global Cancer Program as a priority initiative. In developing the Global Cancer Program, we galvanized institutional support to foster sustained, bidirectional, equitable, international partnerships in global cancer control. Our focus and intent in disseminating this commentary is to share experiences and lessons learned from the perspective of a US-based, National Cancer Institute-designated cancer center and to provide a roadmap for other high-income institutions seeking to strategically broaden their missions and address the complex challenges of global cancer control. Herein, we review the formative evaluation, governance, strategic planning, investments in career development, funding sources, program evaluation, and lessons learned. Reflecting on the evolution of our program during the first 5 years, we observed in our partners a powerful shift toward a locally driven priority setting, reduced dependency, and an increased commitment to research as a path to improve cancer outcomes in resource-constrained settings.

Autologous neutralizing antibodies increase with early antiretroviral therapy and shape HIV rebound after treatment interruption.

Early initiation of antiretroviral therapy (ART) alters viral rebound kinetics after analytic treatment interruption (ATI) and may play a role in promoting HIV-1 remission. Autologous neutralizing antibodies (aNAbs) represent a key adaptive immune response in people living with HIV-1. We aimed to investigate the role of aNAbs in shaping post-ATI HIV-1 rebound variants. We performed single-genome amplification of HIV-1 env from pre-ART and post-ATI plasma samples of 12 individuals who initiated ART early after infection. aNAb activity was quantified using pseudoviruses derived from the most common plasma variant, and the serum dilution that inhibited 50% of viral infections was determined. aNAb responses matured while participants were on suppressive ART, because on-ART plasma and purified immunoglobulin G (IgG) demonstrated improved neutralizing activity against pre-ART HIV-1 strains when compared with pre-ART plasma or purified IgG. Post-ATI aNAb responses exerted selective pressure on the rebounding viruses, because the post-ATI HIV-1 strains were more resistant to post-ATI plasma neutralization compared with the pre-ART virus. Several pre-ATI features distinguished post-treatment controllers from noncontrollers, including an infecting HIV-1 sequence that was more similar to consensus HIV-1 subtype B, more restricted proviral diversity, and a stronger aNAb response. Post-treatment control was also associated with the evolution of distinct N-glycosylation profiles in the HIV-1 envelope. In summary, aNAb responses appeared to mature after early initiation of ART and applied selective pressure on rebounding viruses. The combination of aNAb activity with select HIV-1 sequence and reservoir features identified individuals with a greater chance of post-treatment control.

Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel.

CONTEXT: New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected adults in resource-rich settings. OBJECTIVE: To provide current recommendations for the treatment of adult HIV infection with ART and use of laboratory-monitoring tools. Guidelines include when to start therapy and with what drugs, monitoring for response and toxic effects, special considerations in therapy, and managing antiretroviral failure. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Data that had been published or presented in abstract form at scientific conferences in the past 2 years were systematically searched and reviewed by an International Antiviral Society-USA panel. The panel reviewed available evidence and formed recommendations by full panel consensus. DATA SYNTHESIS: Treatment is recommended for all adults with HIV infection; the strength of the recommendation and the quality of the evidence increase with decreasing CD4 cell count and the presence of certain concurrent conditions. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir). Alternatives in each class are recommended for patients with or at risk of certain concurrent conditions. CD4 cell count and HIV-1 RNA level should be monitored, as should engagement in care, ART adherence, HIV drug resistance, and quality-of-care indicators. Reasons for regimen switching include virologic, immunologic, or clinical failure and drug toxicity or intolerance. Confirmed treatment failure should be addressed promptly and multiple factors considered. CONCLUSION: New recommendations for HIV patient care include offering ART to all patients regardless of CD4 cell count, changes in therapeutic options, and modifications in the timing and choice of ART in the setting of opportunistic illnesses such as cryptococcal disease and tuberculosis.