We report the first case to quantitatively demonstrate a rapid and substantial viral load reduction using long-acting cabotegravir and rilpivirine in the third trimester of pregnancy. This case underscores the challenges some pregnant individuals face with daily oral antiretroviral therapy and the potential role of long-acting injectables in select scenarios.

BACKGROUND:Outside of randomized controlled trials, there are limited data regarding the acceptability of injectable long-acting cabotegravir + rilpivirine (LA-CAB+RPV) among persons living with HIV. To evaluate acceptability, we described participant-reported outcomes of LA-CAB+RPV among a population underrepresented in randomized controlled trials. SETTING:Ruth M. Rothstein Core Center (CORE), large urban HIV clinic in Chicago, IL, USA. METHODS:We interviewed persons living with HIV prescribed LA-CAB+RPV who receive primary care at CORE. Participant-reported outcome endpoints included treatment satisfaction, reasons for switching to LA-CAB+RPV, tolerability of injections, and unexpected effects of LA-CAB+RPV. Mean and standard deviations (mean ± SD) and proportions (%) are reported. RESULTS:Among respondents (N = 150), 67% identified as non-Hispanic Black, 24% Hispanic, 56% male; the average age was 43 years (SD: 13.2), and 37% were ≥50 years old. Most respondents (93%) completed ≥3 injection appointments at the time of interview. The most common reasons for switching to LA-CAB+RPV were no longer wanting to take pills (89%) and trouble taking their pills daily (58%). Treatment satisfaction was high (6.7 ± 0.5 out of 7). Two-thirds (61%) reported an unexpected aspect of their life improved. Pain from injections was common (89%), with a mean pain score of 4.3 out of 10. Among those reporting pain, half (47%) reported that pain decreased after initial injection. Among participants reporting pain score >6 (n = 36), most (78%) reported no improvement since initial injection. CONCLUSIONS:We found high treatment satisfaction with LA-CAB+RPV in a diverse population. Participants reported moderate injection pain, which improved with time. Results suggest injectable LA-CAB+RPV will be met with acceptability across diverse participant populations.

HIV integrase strand transfer inhibitors (INSTI) are considered well tolerated with few treatment-limiting adverse effects. However, emerging data from clinical trials has identified excessive weight gain possibly due to INSTI alone or with tenofovir alafenamide as a new and possible long-term complication of combination antiretroviral therapy (cART). Identifying who is at greatest risk and whether the unintended weight gain is reversible remain unanswered questions. We report a return to baseline weight after switching back to tenofovir disoproxil/emtricitabine/efavirenz (Atripla®) in a woman who had profound weight gain due to tenofovir alafenamide/emtricitabine/cobicistat/elvitegravir (Genvoya®).

Persons living with HIV/AIDS (PLWHA) are at higher risk of developing adverse cutaneous reactions compared to the general population [1,2]. Numerous antiretrovirals approved for HIV treatment are associated with adverse dermatological reactions such as non-nucleoside reverse transcriptase inhibitors, protease inhibitors (specifically darunavir and amprenavir), and the CD4 T-lymphocyte attachment inhibitor ibalizumab [3]. Some antiretrovirals are associated with hypersensitivity reaction, one example is PLWHA who test positive for HLA-B*5701 allele and are prescribed the nucleoside reverse transcriptase inhibitor abacavir.

It has been over 30 years since the first antiretroviral agent was approved for treatment of HIV-1 infection and its impact on morbidity and mortality has been dramatic. However, early treatments were hindered by short- and long-term toxicity, poor tolerability, high pill burden, drug interactions and development of drug resistance. A major breakthrough in HIV therapeutics occurred over a decade ago with a new class of drugs that not only are preferred by HIV treatment guidelines but also are changing the HIV treatment paradigm. This new class of drugs are called HIV-1 integrase strand transfer inhibitors and they have established a role in almost every aspect of HIV treatment.

Selection of an appropriate antiretroviral regimen for the patient infected with human immunodeficiency virus can be challenging, as various considerations must be taken into account including viral resistance mutations, patient comorbidities, drug interactions, and the potential for drug-related adverse effects and toxicities. Treatment is further complicated when a clinical scenario arises requiring an alteration in the dosage form. Factors ranging from dysphagia to administration through an enteral feeding tube can affect decisions regarding antiretroviral dosage forms. Limited pharmacokinetic data exist regarding the alteration of antiretroviral medications from their original form. Bioavailability may vary substantially between dosage forms, which can lead to unpredictable drug concentrations. Supratherapeutic or subtherapeutic antiretroviral drug concentrations can result in increased toxicity, virologic failure, or the emergence of drug resistance. We performed a systematic literature search to review the available antiretroviral literature on the modification of solid dosage forms as well as alternative routes of administration of oral antiretroviral agents and their application to clinical practice.

Dolutegravir is a second-generation HIV integrase strand transfer inhibitor (INSTI) and the most recent antiretroviral approved for treatment of HIV-1 infection. Dolutegravir in combination with two nucleoside reverse transcriptase inhibitors is one of the preferred regimens recommended by the Department of Health and Human Services HIV treatment guidelines for treatment-naive adults and adolescents. This recommendation is based on clinical trial data where dolutegravir demonstrated superiority compared with guideline preferred regimens containing efavirenz and ritonavir-boosted darunavir and noninferiority compared with first-generation INSTI, raltegravir. Dolutegravir also demonstrated superiority when compared with raltegravir in treatment-experienced, integrase-naive patients and clinical efficacy in patients with resistance to first-generation INSTIs. Overall, dolutegravir has demonstrated excellent tolerability, limited drug interactions, minimal drug resistance and once-daily dosing for treatment-naive patients.

BACKGROUNDTenofovir associated nephrotoxicity (TDFN) is well recognized. This study describes the trend of renal function recovery and virologic consequences after cessation of tenofovir (TDF) for suspected TDFN.METHODSThis was a retrospective chart review of 241 patients who underwent HLA-B*5701 allele testing between January 2007-December 2010. Demographics and clinical characteristics were compared at baseline, 3, 6, and 12 month between patients that continued and discontinued TDF. Factors associated with renal function recovery were assessed by multivariable logistic regression.RESULTSEighty patients were identified with TDFN; 84% male, 74% African American (AA) with a median age of 55 years, and median length of TDF use for 122 weeks. Renal recovery at 12 months differed in those who stopped versus (vs.) continued TDF (83% vs. 57% p=0.03). In a crude analysis, baseline chronic kidney disease was negatively associated with renal recovery (p=0.01). An adjusted analysis showed that those who stopped TDF had 3.76 higher odds of renal recovery compared to those who did not stop TDF (95% CI: 1.26-11.27, p=0.02). There were no significant differences in virologic response after switching TDF to an alternative agent.CONCLUSIONIn this mostly AA male population with suspected TDFN, discontinuation of TDF was strongly associated with renal function recovery without affecting viral suppression.

We describe a 55-year-old HIV-1-infected male who developed severe dyslipidaemia (total cholesterol 600 mg/dl, triglycerides >5,000 mg/dl, high density lipoprotein <5 mg/dl) after raltegravir was added to his lopinavir/ ritonavir-containing regimen. To our knowledge, this is the first reported case of severe dyslipidaemia associated with the addition of raltegravir to a lopinavir/ritonavir-based regimen, suggestive of a possible drug interaction. The lipid profile quickly normalized following discontinuation of lopinavir/ritonavir and continuation of raltegravir, suggesting that lopinavir/ritonavir was the primary driver for the adverse event. With increasing interest in nucleoside-sparing regimens, knowledge of clinically significant adverse events such as this is important for HIV clinicians when selecting regimens for patients with highly resistant virus or drug tolerability issues.

Morbidity and mortality associated with human immunodeficiency virus (HIV) has decreased with highly active anti-retroviral therapy (HAART). Tenofovir is a nucleotide reverse transcriptase inhibitor (NRTI) that is preferred by the Department of Health and Human Services (DHHS) HIV treatment guidelines and is widely used for the initial treatment of HIV. Although tenofovir is generally well-tolerated, it has been associated with rare cases of acute nephrotoxicity. HIV-infected patients frequently have co-morbidities that require treatment, thus adding another level of complexity due to drug interactions and medication adverse effects with antiretrovirals. We present a patient who suffered an acute deterioration in renal function from tenofovir, leading to an accumulation of co-administered ethambutol, thus resulting in optic neuritis.

Venous thrombosis is a well-described complication of thalidomide therapy in patients with multiple myeloma (MM). However, an association between thalidomide use and thrombosis in HIV-positive patients has not been previously described. We present the case of a 48-year-old HIV-positive man who developed a deep venous thrombosis while on thalidomide for the treatment of severe aphthous ulcers. We review the management of severe aphthous disease and the potential adverse effects of thalidomide therapy. We examine the association between thalidomide and thrombosis in patients with MM and discuss how the same relationship may or may not exist in HIV-positive patients. Although the strength of the association between thalidomide use and thrombosis in HIV-positive patients being treated for aphthous disease remains unclear, HIV providers should be aware of the potential risk of thrombosis in all patients receiving thalidomide.

BACKGROUND:In the HAART era, the incidence of HIV-associated non-Hodgkin lymphoma (NHL) is decreasing. We describe cases of NHL among patients with multi-class antiretroviral resistance diagnosed rapidly after initiating newer-class antiretrovirals, and examine the immunologic and virologic factors associated with potential IRIS-mediated NHL.METHODS:During December 2006 to January 2008, eligible HIV-infected patients from two affiliated clinics accessed Expanded Access Program antiretrovirals of raltegravir, etravirine, and/or maraviroc with optimized background. A NHL case was defined as a pathologically-confirmed tissue diagnosis in a patient without prior NHL developing symptoms after starting newer-class antiretrovirals. Mean change in CD4 and log10 VL in NHL cases compared to controls was analyzed at week 12, a time point at which values were collected among all cases.RESULTS:Five cases occurred among 78 patients (mean incidence = 64.1/1000 patient-years). All cases received raltegravir and one received etravirine. Median symptom onset from newer-class antiretroviral initiation was 5 weeks. At baseline, the median CD4 and VL for NHL cases (n = 5) versus controls (n = 73) were 44 vs.117 cells/mm3 (p = 0.09) and 5.2 vs. 4.2 log10 (p = 0.06), respectively. The mean increase in CD4 at week 12 in NHL cases compared to controls was 13 (n = 5) vs. 74 (n = 50)(p = 0.284). Mean VL log10 reduction in NHL cases versus controls at week 12 was 2.79 (n = 5) vs. 1.94 (n = 50)(p = 0.045).CONCLUSIONS:An unexpectedly high rate of NHL was detected among treatment-experienced patients achieving a high level of virologic response with newer-class antiretrovirals. We observed trends toward lower baseline CD4 and higher baseline VL in NHL cases, with a significantly greater decline in VL among cases by 12 weeks. HIV-related NHL can occur in the setting of immune reconstitution. Potential immunologic, virologic, and newer-class antiretroviral-specific factors associated with rapid development of NHL warrants further investigation.

We determined rates of achieving the American Diabetes Association goals among human immunodeficiency virus (HIV)-infected diabetic patients. American Diabetes Association goals ( for hemoglobin A1c, blood pressure, and lipid levels) were defined by 2008 American Diabetes Association guidelines. HIV-infected diabetic patients achieved American Diabetes Association goals at rates similar to those in general medicine clinic patients. A multidisciplinary approach is needed to improve diabetes management in HIV clinics.

INTRODUCTION:To explore whether an assay change was responsible for an increasing proportion of patients with undetectable HIV viral loads at our urban HIV clinic, we selected highly stable patients, examining their viral loads before and after changing assays. We compared the proportion with detectable viremia during RT-PCR vs. bDNA periods. METHODOLOGY/PRINCIPAL FINDINGS:We selected patients with > or =1 viral loads assessed during both RT-PCR and bDNA periods. We included patients with stable CD4 counts, excluding patients with viral loads > or =1,000 copies/ml or any significant changes in therapy. Out of 4500 clinic patients, 419 patients (1588 viral loads) were included. 39% of viral loads were reported as detectable by RT-PCR vs. 5% reported as detectable by bDNA. The mean coefficient of variation was higher before vs. after assay change. We found an odds' ratio of 16.7 for having a viral load >75 copies/ml during the RT-PCR vs. bDNA periods. DISCUSSION:These data support previous reports, suggesting that bDNA may more reliably discriminate between viral suppression and low level viremia in stable patients on therapy. Low-level viremia, noted more with RT-PCR, may promote unneeded testing, while differences in viral load reliability may impact antiretroviral trial and quality assurance endpoints. Commonly used plasma separator tubes may differentially affect RT-PCR and bDNA results.