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Background A prespecified integrated safety analysis was conducted for 3 doravirine (DOR) double-blind trials (Phase IIb: P007 [NCT01632345]; Phase III: DRIVE-FORWARD [NCT02275780] and DRIVE-AHEAD [NCT02403674]). Methods DOR (100 mg) arms from these trials were compared with darunavir plus ritonavir (DRV+r) in DRIVE-FORWARD and efavirenz (EFV) in P007 and DRIVE-AHEAD. Background therapies were emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in P007; abacavir/lamivudine (ABC/3TC) or FTC/TDF in DRIVE-FORWARD; and 3TC/TDF for DOR and FTC/TDF for EFV in DRIVE-AHEAD. The primary endpoint was the proportion of participants discontinuing due to adverse events (AEs) through Week 48. Results Discontinuation rates due to AEs were similar for participants on DOR and DRV+r (2.5% vs 3.1%, respectively) and lower for those on DOR than for those on EFV (2.5% vs 6.6%, respectively). Rates of drug-related AEs for DOR, DRV+r, and EFV were 30.9%, 32.1%, and 61.4%, respectively. In an analysis of DOR versus EFV, the treatment difference for discontinuations due to AEs was −3.4%, favoring DOR (95% confidence interval −6.2 to −0.8; P =.012). Fewer participants experienced neuropsychiatric AEs on DOR than on EFV (25.0% vs 55.9%, respectively), and fewer experienced diarrhea on DOR than on DRV+r (12.4% vs 22.5%, respectively). Changes from baseline in most lipid parameters also favored DOR. Conclusions At Week 48, DOR at 100 mg had a favorable safety profile compared with EFV or DRV+r and a favorable tolerability profile compared with EFV. Clinical Trials Registration NCT01632345; NCT02275780 and NCT02403674. [ABSTRACT FROM AUTHOR]

The article focuses on the 2012 recommendations of the Intemational Antiviral Society for the antiretroviral treatment (ART) of adult HIV infection. It states that the new recommendations for HIV patient care include providing ART to all patients regardless of CD4 cell count, changes in therapeutic options, and modifications in the timing. It also recommends providing ART irrespective of the choice of ART in the setting of opportunistic illnesses such as cryptococcal disease and tuberculosis. It also states that the concentration of HIV in both blood and seminal plasma is related to the probability of transmission of HIV to a sexual partner.

Few studies have examined the psychosocial factors associated with sexual transmission behaviors among HIV-positive men who have sex with men (MSM), heterosexual men (MSW) and women. We enrolled 1,050 sexually active HIV-positive patients at seven HIV clinics in six US cities as part of a clinic-based behavioral intervention. We describe the sexual transmission behaviors and examine demographic, clinical, psychosocial, and clinic prevention variables associated with unprotected anal or vaginal intercourse (UAVI). Twenty-three percent of MSM, 12.3% of MSW and 27.8% of women engaged in UAVI with partners perceived to be HIV-negative or of unknown serostatus. Among MSM and MSW, having multiple partners and lower self-efficacy were associated with increased odds of UAVI. Self-rating one’s health status as excellent/very good was a risk factor for UAVI among MSM. Among women, binge drinking and stressful life events were associated with UAVI. These findings identify variables that warrant attention in targeted interventions. [ABSTRACT FROM AUTHOR]

The article looks at the attitudes and counseling practices of HIV care providers before and after being trained to deliver counseling interventions to patients. Results indicate that the self-ratings of HIV care providers improved following training, particularly in the areas of attitudes, self-efficacy, comfort, and frequency of delivering prevention counseling. The author also notes that patients of HIV care clinics reported an increase in prevention counseling following the training of their providers.

The article reports on research which was conducted in an effort to summarize new data in the field of antiretroviral treatment of adult HIV infection and to provide current recommendations for antiretroviral management and monitoring of HIV infection. Researchers found that new data and considerations support initiating therapy before CD4 cell counts decline to less than 350/ul. They also determined that the initial treatment regimen for patients must be individualized, particularly in the presence of comorbid conditions. Their findings on treatment failure are discussed.

We conducted a demonstration project to design, implement, and evaluate a risk-reduction intervention delivered by medical providers to patients with HIV during routine care in 2005 and 2006. Medical providers at seven HIV clinics in the United States received training to deliver an intervention in which they screened patients for behavioral risks, gave targeted counseling, and delivered prevention messages. A longitudinal cohort ( n = 767) of patients completed a baseline questionnaire and two follow-up questionnaires (6-month intervals) after the intervention was initiated. Logistic regression and generalized estimating equations (GEE) methods were used in analyses. The cohort had a median age of 41, was 58% black, 28% white, and 10% Hispanic; 32% were women and 42% self-identified as men who have sex with men. The 3-month prevalence of unprotected anal or vaginal intercourse (UAVI) with any partners declined significantly ( p < 0.001) from baseline (42%) to follow-up (26% at first follow-up, 23% at second follow-up). The decline was significant with partners who were HIV-negative/unknown serostatus or HIV-positive. Cohort patients' self-reported receipt of safer-sex counseling at all, some, or no clinic visits during the interval between baseline and first follow-up showed a dose-response relationship with decline in prevalence of UAVI in that interval, with relative reductions of 45%, 35%, and 19%, respectively. All findings were confirmed in multivariate models that controlled for demographic factors and HIV clinical status of participants. This project demonstrated that with only brief training, HIV medical providers successfully conducted an HIV prevention intervention with their clinic patients. Our findings indicate that clinics that serve HIV patients can incorporate such programs as standard of care. [ABSTRACT FROM AUTHOR]

Studies the impact of an educational program on efficacy and adherence with a twice-daily lamivudine/zidovudine/abacavir regimen in underrepresented HIV-infected patients. Modules of the Tools or Health and Empowerment HIV education intervention; Plasma HIV-1 RNA levels.

Assesses the risk of AIDS-related opportunistic illness or death among persons first prescribed highly active antiretroviral therapy in the U.S. Increase of HIV plasma RNA levels; Improvement of the quality of life of HIV-infected persons; Cause of the decrease of CD4[sup +] lymphocyte counts.

A 48-week open-label study of 11 antiretroviral-naive, human immunodeficiency virus type 1 (HIV-1)-infected adults evaluated once-daily treatment with adefovir dipivoxil, lamivudine, didanosine, and efavirenz. At baseline, the median plasma HIV-1 RNA level was 4.99 log[sub 10] copies/mL, and the median CD4 cell count was 471 cells/mm[sup 3]. At 24 and 48 weeks after initiation of treatment, median HIV-1 RNA levels decreased from baseline by 4.77 and 4.99 log[sub 10] copies/mL, respectively, and median CD4 cell counts increased by 135 and 177 cells/mm[sup 3], respectively. The regimen was generally well tolerated. No patients withdrew from the study because of adverse events. However, 7 patients developed adefovir-related nephrotoxicity after ≥20 weeks of treatment; this resolved without sequelae after adefovir was discontinued. Overall adherence was 85%. Once-daily quadruple-drug therapy with adefovir, lamivudine, didanosine, and efavirenz provides pronounced and durable suppression of HIV-1 RNA and elevation of CD4 cell counts over the course of 48 weeks, with generally good tolerability and adherence. [ABSTRACT FROM AUTHOR]

Introduction Doravirine (DOR) is an investigational NNRTI (aka MK-1439) that retains activity against common NNRTI-resistant mutants. We have previously reported the Part 1 results from a two-part, randomized, double-blind, Phase IIb study in ART-naïve HIV-1-positive patients []. At doses of 25, 50, 100 and 200 mg qd, DOR plus open-label tenofovir/emtricitabine (TDF/FTC) demonstrated potent antiretroviral activity comparable to EFV 600 mg qhs plus TDF/FTC and was generally well tolerated at week 24. DOR 100 mg was selected for use in patients continuing in Part 1 and those newly enrolled in Part 2. Methods Patients receiving DOR 25, 50 or 200 mg in Part 1 were switched to 100 mg after dose selection. In Part 2, 132 additional patients were randomized 1:1 to DOR 100 mg qd or EFV 600 mg qhs (each with TDF/FTC). We present week 48 efficacy and safety results for all patients in Part 1, and early (week 8) CNS tolerability only for patients randomized to DOR 100 mg or to EFV in Parts 1 and 2 combined. The primary safety endpoint is the % of patients with pre-specified CNS events (all causality) by week 8 for DOR 100 mg qd vs EFV (Parts 1 + 2 combined). Results Part 1 week 48 efficacy and safety results are shown below. The most common DR clinical AEs in the DOR and EFV groups, respectively, were abnormal dreams (10.2%; 9.5%), nausea (7.8%; 2.4%), fatigue (7.2%; 4.8%), diarrhoea (4.8%; 9.5%) and dizziness (3.0%; 23.8%), and were generally mild to moderate. Part 1 + 2 Week 8 CNS Event Analysis: One hundred thirty-two patients were randomized in Part 2, 66 to DOR 100 mg and 66 to EFV. Combining Part 1 and 2, a total of 108 patients received DOR 100 mg and 108 received EFV. By week 8, at least one CNS AE was reported in 22.2% of the DOR group and 43.5% of the EFV group ( p<0.001). The most common CNS AEs were dizziness (DOR 9.3%; EFV 27.8%), insomnia (6.5%; 2.8%), abnormal dreams (5.6%; 16.7%) and nightmares (5.6%; 8.3%). Conclusions In ART-naïve, HIV-1-positive patients also receiving TDF/FTC, DOR 100 mg qd demonstrated potent antiretroviral activity and immunological effect at week 48 and was generally safe and well tolerated. Patients who received DOR 100 mg qd had significantly fewer treatment-emergent CNS AEs by week 8 than those who received EFV. [ABSTRACT FROM AUTHOR]

Describes the factors that complicate anti-tuberculosis therapy in a large observational cohort of HIV-infected persons in the United States. Hepatotoxicity; Adverse events; Elevation of the upper limits of normal of aminotransaminases.

Background: We compared two combinations of nucleosides with zidovudine alone in patients with advanced human immunodeficiency virus (HIV) infection. Methods: A total of 1102 patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter were randomly assigned to receive zidovudine alone or zidovudine combined with either didanosine or zalcitabine. Disease progression, survival, toxic effects, and the CD4 cell response were assessed. Results: After a median follow-up of 35 months, disease progression or death occurred in 62 percent of the 363 patients assigned to zidovudine plus didanosine, 63 percent of the 367 assigned to zidovudine plus zalcitabine, and 66 percent of the 372 assigned to zidovudine alone (P = 0.24). As compared with zidovudine therapy, treatment with zidovudine plus didanosine was associated with a relative risk of disease progression or death of 0.86 (95 percent confidence interval, 0.71 to 1.03), and treatment with zidovudine plus zalcitabine was associated with a relative risk of 0.92 (95 percent confidence interval, 0.76 to 1.10). Survival was similar in the three groups. In a subgroup analysis, combination therapy delayed disease progression or death in patients who had previously received zidovudine for 12 months or less. Therapy with zidovudine plus didanosine resulted in more gastrointestinal adverse effects, and treatment with zidovudine plus zalcitabine, more neuropathy. The mean increases in CD4 cell counts at two months were higher with combination therapy than with zidovudine alone. Conclusions: In patients with advanced HIV infection, combination therapy with zidovudine and either didanosine or zalcitabine is not superior to zidovudine therapy alone. However, these combinations may be more effective than zidovudine monotherapy in patients with little or no previous zidovudine treatment. (N Engl J Med 1996;335:1099-106.) [ABSTRACT FROM AUTHOR]

Background: Both didanosine and zalcitabine are commonly used to treat patients with human immunodeficiency virus (HIV) infection who cannot tolerate zidovudine treatment or who have had disease progression despite it. The relative efficacy and safety of these second-line therapies are not well defined. Methods: In this multicenter, open-label trial we randomly assigned 467 patients who previously received zidovudine and had 300 or fewer CD4 cells per cubic millimeter or a diagnosis of the acquired immunodeficiency syndrome (AIDS) to treatment with either didanosine (500 mg per day) or zalcitabine (2.25 mg per day). Results: After a median follow-up of 16 months, disease progression or death occurred in 157 of 230 patients assigned to didanosine and 152 of 237 patients assigned to zalcitabine, for a relative risk of 0.93 for the zalcitabine group as compared with the didanosine group (P = 0.56), which decreased to 0.84 (P = 0.15) after adjustment for the CD4 count, Karnofsky score, and presence of AIDS at base line. There were 100 deaths in the didanosine group and 88 in the zalcitabine group, for a relative risk of 0.78 (P = 0.09) and an adjusted relative risk of 0.63 (P = 0.003). A majority of patients in each group (66 percent) had at least one adverse event during treatment (153 patients taking didanosine and 157 taking zalcitabine). Peripheral neuropathy and stomatitis occurred more often with zalcitabine and diarrhea and abdominal pain more frequently with didanosine. Conclusions: For patients with HIV infection who have not responded to treatment with zidovudine, zalcitabine is at least as efficacious as didanosine in delaying disease progression and death. (N Engl J Med 1994;330:657-62.) [ABSTRACT FROM AUTHOR]