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Supplemental Digital Content is Available in the Text., Ibalizumab, a humanized monoclonal antibody targeting CD4, blocks HIV-1 entry into cells and is the first Food and Drug Adminstration-approved long-acting agent for HIV-1 treatment. In this phase 2a study, 82 HIV-infected adults failing antiretroviral therapy were assigned an individually optimized background regimen (OBR) and randomized 1:1:1 to arm A (15 mg/kg ibalizumab q2wk), arm B (10 mg/kg weekly for 9 weeks, then q2wk), or placebo. Subjects with an inadequate response at week 16 were permitted to cross over to a new OBR plus 15 mg/kg ibalizumab q2wk. At week 16, viral load (VL) reduction was significantly greater than placebo (0.26 log10) in arms A (1.07 log10; P = 0.002) and B (1.33 log10; P < 0.001); CD4+ T cell counts increased significantly in arm A. After week 16, 11/27 (arm B) and 19/27 (placebo) subjects crossed over to OBR plus 15 mg/kg ibalizumab; 8/28 in arm A initiated a new OBR. Ibalizumab treatment resulted in VL reduction at week 24 (−0.77 and −1.19 log10 for arms A and B, respectively, versus −0.32 log10 for placebo) and 48 weeks (−0.54 and −0.77 versus −0.22 log10). Compared with placebo, VL differences were statistically significant for arm B at week 24 (P = 0.001) and week 48 (P = 0.027). CD4+ T cell counts increased significantly by week 48 in both arm A and arm B, relative to placebo. No ibalizumab-related serious adverse events were reported. The durable antiviral activity and tolerability of ibalizumab support its use in treating individuals harboring multidrug-resistant HIV-1.

Summary Background Doravirine is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) with a pharmacokinetic profile supporting once-daily dosing, and potent in-vitro activity against the most common NNRTI-resistant HIV-1 variants. We compared doravirine with ritonavir-boosted darunavir, when both were given with two nucleoside reverse transcriptase inhibitors (NRTIs), in adults with previously untreated HIV-1 infection. Methods In this randomised, controlled, double-blind, multicentre, non-inferiority trial, adults with HIV-1 infection were screened and enrolled at 125 clinical centres in 15 countries. Eligible participants (aged ≥18 years) were naive to antiretroviral therapy with plasma HIV-1 RNA of at least 1000 copies per mL at screening. Participants who had previously been treated for a viral infection other than HIV-1, those taking immunosuppressive drugs, and individuals with active acute hepatitis were excluded. Participants were randomly assigned (1:1) via an interactive voice and web response system to receive oral doravirine 100 mg or darunavir 800 mg plus ritonavir 100 mg once daily, with two investigator-selected NRTIs (tenofovir and emtricitabine or abacavir and lamivudine) for up to 96 weeks. Randomisation was stratified by HIV-1 RNA measurements at screening (≤100 000 vs >100 000 copies per mL) and the NRTI pair. Study participants, funding institution staff, investigators, and study site personnel were masked to treatment group assignment. The primary efficacy endpoint was the proportion of participants achieving HIV-1 RNA of less than 50 copies per mL at week 48 defined by the US Food and Drug Administration snapshot algorithm, with non-inferiority established if the lower bound of the two-sided 95% CI for the treatment difference (doravirine minus darunavir) was greater than −10 percentage points. All participants who received at least one dose of study drug were included in the primary efficacy and safety analyses. This trial is active, but not recruiting, and is registered with ClinicalTrials.gov, number NCT02275780. Findings Between Dec 1, 2014, and Oct 20, 2015, 1027 participants were screened for eligibility, of whom 769 participants were randomly assigned to treatment (385 with doravirine and 384 with ritonavir-boosted darunavir). 56 participants discontinued treatment in the doravirine group compared with 71 in the darunavir group, mostly due to loss to follow-up. 383 participants who received doravirine and 383 who received darunavir were included in the primary efficacy analyses. At week 48, 321 (84%) participants in the doravirine group and 306 (80%) in the darunavir group achieved plasma HIV-1 RNA of less than 50 copies per mL (difference 3·9%, 95% CI −1·6 to 9·4), indicating non-inferiority of the doravirine regimen. The most common study drug-related adverse events were diarrhoea (21 [5%] of 383 participants in the doravirine group and 49 [13%] of 383 participants in the darunavir group), nausea (25 [7%] vs 29 [8%]), and headache (23 [6%] vs ten [3%]). 18 participants (six [2%] of 383 participants in the doravirine group vs 12 [3%] of 383 participants in the darunavir group) discontinued treatment due to adverse events, which were considered drug-related in four (1%) participants in the doravirine group and 8 (2%) participants in the darunavir group. Serious adverse events occurred in 19 (5%) of 383 participants in the doravirine group and 23 (6%) of 383 in the darunavir roup, and were considered study-drug related in one ( Interpretation In treatment-naive adults with HIV-1 infection, doravirine combined with two NRTIs might offer a valuable treatment option for adults with previously untreated HIV-1 infection. Funding Merck & Co.

Summary Background Dolutegravir is a once-daily integrase strand transfer inhibitor with no need for pharmacokinetic boosting that is approved for the treatment of HIV-1 infection. Because women are often under-represented in HIV clinical trials, we addressed the safety and efficacy of dolutegravir in women with HIV-1. Methods The ARIA study is a randomised, open-label, multicentre, active-controlled, parallel-group, non-inferiority phase 3b study done in 86 hospital and university infectious disease clinics, local health clinics, and private infectious disease clinics in 12 countries and one US territory, in North America, South America, Europe, Africa, and Asia. Eligible participants were women aged 18 years or older who had HIV-1 RNA viral loads of 500 copies per mL or greater, had received 10 days or less of previous antiretroviral therapy, and had tested negative for the HLA-B*5701 allele. Pregnant women were excluded. Eligible women were randomly assigned (1:1) to receive either a single-tablet regimen of dolutegravir plus abacavir and lamivudine once a day (dolutegravir group) or a three-tablet combination of ritonavir-boosted atazanavir plus coformulated tenofovir disoproxil fumarate and emtricitabine once a day (atazanavir group). Random treatment group assignment was stratified by plasma HIV-1 RNA viral loads and CD4 cell count at baseline. The primary endpoint was the proportion of participants with HIV-1 RNA viral loads of less than 50 copies per mL at week 48 in all participants who received at least one dose of study medication (intention-to-treat exposed population). We used a non-inferiority margin of −12%. Investigators monitored adverse events to assess safety. This study is registered with ClinicalTrials.gov, number NCT01910402. Findings Between Aug 22, 2013, and Sept 22, 2015, of 705 women assessed, 499 were randomly assigned to either the dolutegravir group (n=250) or the atazanavir group (n=249); two participants from each group were randomised to treatment but did not receive study medication. At week 48, 203 (82%) of 248 participants in the dolutegravir group compared with 176 (71%) of 247 in the atazanavir group had HIV-1 RNA viral loads of less than 50 copies per mL (mean difference 10·5%, 95% CI 3·1–17·8, p=0·005). One participant in the atazanavir group had nucleoside reverse transcriptase inhibitor–associated resistance that led to reduced emtricitabine susceptibility. Adverse events were similar between the dolutegravir and atazanavir groups; the most common were nausea (46 [19%] of 248 in the dolutegravir group vs 49 [20%] of 247 in the atazanavir group) and headache (28 [11%] vs 32 [13%]). Fewer participants in the dolutegravir group than the atazanavir group reported drug-related adverse events (83 [33%] vs 121 [49%]) or adverse events that led to discontinuation (ten [4%] vs 17 [7%]). One death was reported in each treatment group, but neither was considered related to the study medications. Interpretation The non-inferior efficacy and similar safety profile of the dolutegravir combined regimen compared with the atazanavir regimen support the use of dolutegravir for HIV-1 infection in treatment-naive women. Funding ViiV Healthcare.

This study examined whether melanonychia was more prevalent in 1) HIV positive individuals compared to HIV negative persons, 2) HIV positives exposed to zidovudine and/or stavudine and 3) those with darker skin pigmentation. Procedures. 267 HIV positive and 273 HIV negative patients were examined for presence or absence of melanonychia and level of skin pigmentation using the Fitzgerald scale. Pharmacy records were examined for determining exposure to zidovudine or stavudine. Chi square, odds ratios and logistic regression were used to examine the study questions Main Findings. Melanonychia appeared in 49.1% of 267 HIV positive and 21.8% of 273 HIV negative subjects. Adjusting for skin pigmentation, HIV positives were 4.1 times more likely to have melanonychia than HIV negatives. Melanonychia was present in 54% of those receiving zidovudine and in 42% of those receiving stavudine (OR = 2.73, p = 0.05). In a multivariate model in HIV positives which included skin type, prescription of zidovudine and/or Stavudine, only dark skin (OR = 14.62, p < 0.001) and zidovudine (OR = 2.65, p < 0.03) were significant. Principal Conclusions. HIV infected persons are prone to melanonychia. This is more frequent in darker skinned persons and is enhanced in those exposed to zidovudine.

Studies have shown that reverse transcription-polymerase chain reaction (RT-PCR) technology underquantifies viral loads in patients with non-B clades of HIV-1. Testing with bDNA technology gave higher viral loads in these subtypes. A study was conducted to determine whether virologically responding patients on HAART who were not immunologically responding would have higher viral loads using bDNA technology and whether these differences were due to non-B clades.Forty-eight patients receiving HAART for more than 6 months who were having inappropriate immunologic responses in spite of undetectable or very low viral loads determined by RT-PCR (3000 copies by Roche Amplicor 1.0) were studied. These patients had bDNA viral loads performed. All patients who had bDNA viral loads equivalent to3000 by RT-PCR had clade and genotypic studies performed.Fifteen patients had viral loads by bDNA that were equivalent to3000 copies by RT-PCR. Four of these were found to have non-B clades (one D clade and three AG clade). The D clade patient had multidrug resistance; none of the AG clade patients had resistance. Of the remaining 11 patients, virus could not be recovered from 2 and 9 had a B clade. Six of these nine had genotypic resistance to HAART drugs.bDNA testing may be useful in the immunologically nonresponding patient.

Dyslipidemia is common in persons living with HIV infection. Nurse clinicians must be able to recognize lipid abnormalities so that treatment plans can be developed. Managing dyslipidemia must be considered early in the HIV treatment process because certain antiretroviral therapy (ART) regimens, particularly those containing ritonavir, may exacerbate dyslipidemia risk. Statins are the most common medications used to treat dyslipidemia; however, because of drug-drug interactions, some are contraindicated with certain ART drugs. Other statins can be used but require dose adjustments when used with certain ART medications. Non-statin medications such as fibrates, niacin, and omega-3 fatty acid (fish oil) can be used to manage lipids and are discussed. Nurse clinicians should be prepared to discuss with the health care team potential alternative drug regimens for concurrent treatment of HIV infection and dyslipidemia.

The purpose of this study was to determine the effective use of the 2001 Centers for Disease Control and Prevention (CDC) HIV testing recommendations in emergency department settings. A postal questionnaire was distributed to health care providers in emergency departments across the United States to evaluate the rate HIV tests are routinely offered to individuals presenting to emergency departments for care. A total of 223 emergency department providers responded. Results indicated that health care providers generally were not aware that their institutions were located in areas with high HIV seroprevalence rates. Only 3% of the health care providers surveyed claimed they routinely offered an HIV test to everyone who sought care in their emergency department regardless of patients' presentation to care. The conclusion was that, in 2004, testing for HIV in emergency departments was not a priority for those providing care. In general, despite the fact that the CDC 2001 HIV testing guidelines were less universal than the 2006 recommendations, many had not implemented routine HIV testing programs in their emergency departments. The number of patients who use emergency departments for routine care is on the rise, and missed opportunities for offering HIV tests have detrimental effects for the individual as well as for the public health.

There were two study questions: How often do HIV-infected patients present with a medical history or concurrent medication use that might contraindicate the use of one or more antiretroviral drugs? What is the frequency of patients having lifestyle behaviors that might preclude them from successfully following an antiretroviral drug regimen?One hundred patients were given a 52-item questionnaire that asked about their medical histories, concurrent use of non-HAART drugs, and lifestyle. The results were analyzed to determine the frequency of potential side effects, drug interactions, or lifestyle behaviors that could interfere with the patient being able to successfully adhere to antiretroviral drug regimens.96% of the patients had at least one medical history item or were taking at least one medication that could potentially create a serious side effect to one or more of the 14 antiretroviral drugs that were studied. All of the patients had at least one lifestyle behavior that would have interfered with successful adherence to one or more of the drugs.The questionnaire utilized in the study identified potential factors that could cause medical problems or that could interfere with the successful use of various antiretroviral drugs. The frequency of occurrence of these factors was unexpectedly high.

Nathaniel Currier's spectacular lithograph of the “Great Riot at the Astor Place Opera House, New York” (1), is one of the most well-known images depicting a nineteenth-century U.S. theatre building left to us by the popular pictorial reporting of that prephotographic era. The background of the event in terms of drama history is familiar, when It is the building itself, as a theatrical monument, that we tend to overlook, except for its appeal as a bygone relic, and architecturally it is easy to dismiss it as simply another manifestation of the rage which was caustically described by the New York correspondent of The Architectural Magazine (London) in 1834: One factor which discourages the theatre historian is the difficulty of relating any one theatre of the period with other examples in a city, let alone the country.