Non-AIDS comorbidity burden differs by sex, race, and insurance type in aging adults in HIV care.

OBJECTIVE: To understand the epidemiology of non-AIDS-related chronic comorbidities (NACMs) among aging persons with HIV (PWH). DESIGN: Prospective multicenter observational study to assess, in an age-stratified fashion, number and types of NACMs by demographic and HIV factors. METHODS: Eligible participants were seen during 1 January 1997 to 30 June 2015, followed for more than 5 years, received antiretroviral therapy (ART), and virally suppressed (HIV viral load <200 copies/ml ≥75% of observation time). Age was stratified (18-40, 41-50, 51-60, ≥61 years). NACMs included cardiovascular disease, cancer, hypertension, diabetes, dyslipidemia, arthritis, viral hepatitis, anemia, and psychiatric illness. RESULTS: Of 1540 patients, 1247 (81%) were men, 406 (26%) non-Hispanic blacks (NHB), 183 (12%) Hispanics/Latinos, 575 (37%) with public insurance, 939 (61%) MSM, and 125 (8%) with injection drug use history. By age strata 18-40, 41-50, 51-60, and at least 61 years, there were 180, 502, 560, and 298 patients, respectively. Median HIV Outpatient Study observation was 10.8 years (range: min-max = 5.0-18.5). Mean number of NACMs increased with older age category (1.4, 2.1, 3.0, and 3.9, respectively; P < 0.001), as did prevalence of most NACMs (P < 0.001). Age-related differences in NACM numbers were primarily due to anemia, hepatitis C virus infection, and diabetes. Differences (all P < 0.05) in NACM number existed by sex (women >men, 3.9 vs. 3.4), race/ethnicity (NHB >non-NHB, 3.8 vs. 3.4), and insurance status (public >private, 4.3 vs. 3.1). CONCLUSIONS: Age-related increases existed in prevalence and number of NACMs, with disproportionate burden among women, NHBs, and the publicly insured. These groups should be targeted for screening and prevention strategies aimed at NACM reduction.

Daclatasvir and Peginterferon/Ribavirin for Black/African-American and Latino Patients with HCV infection.

 Background. Patient race and ethnicity have historically impacted HCV treatment response. This phase 3 study evaluated daclatasvir with peginterferon-alfa-2a/ribavirin (pegIFN alfa-2a/RBV) in treatment-naive black/African American (AA), Latino, and white non-Latino patients with chronic HCV genotype 1 infection. MATERIAL AND METHODS: In this single-arm, open-label study, 246 patients received daclatasvir plus pegIFN alfa-2a and weight-based RBV. Patients with an extended rapid virologic response (eRVR; undetectable HCV-RNA at treatment weeks 4 and 12) received 24 weeks of treatment; those without eRVR received an additional 24 weeks of treatment with pegIFN alfa-2a/RBV. The primary endpoint was sustained virologic response at post-treatment week 12 (SVR12; HCV-RNA < 25 IU/mL) compared with the cohort historical rate. RESULTS: Most patients were IL28B non-CC (84.4% black/AA; 77.6% Latino) genotype 1a-infected (72.7%; 81.3%), with HCV-RNA ≥ 800,000 IU/mL (81.3%; 64.5%). SVR12 rates were 50.8% (65/128; 95% confidence interval [CI], 42.1-59.4) for black/AA and 58.9% (63/107; 95% CI, 49.6-68.2) for Latino patients. The majority (55.5%; 58.9%) received 24 weeks treatment; rapid reductions (> 4-log10) in HCV-RNA levels were observed. Only 60.9% (78/128) of black/AA and 63.6% (68/107) of Latino patients completed treatment. On-treatment serious adverse events (SAEs) occurred in 21 patients. Discontinuations due to adverse events (AEs) occurred in 9 black/AA and 6 Latino patients. CONCLUSION: SVR12 rates for black/AA (50.8%) and Latino (58.9%) cohorts treated with daclatasvir plus pegIFN alfa-2a/RBV and the lower bound of the 95% CIs were higher than the estimated historical control (black/AA, 26% SVR; Latino, 36% SVR) treated with pegIFN alfa-2a/RBV. These data support daclatasvir use in all-oral direct-acting antiviral combinations.

A Matter of Perspective: Comparison of the Characteristics of Persons with HIV Infection in the United States from the HIV Outpatient Study, Medical Monitoring Project, and National HIV Surveillance System.

Comparative analyses of the characteristics of persons living with HIV infection (PLWH) in the United States (US) captured in surveillance and other observational databases are few. To explore potential joint data use to guide HIV treatment and prevention in the US, we examined three CDC-funded data sources in 2012: the HIV Outpatient Study (HOPS), a multisite longitudinal cohort; the Medical Monitoring Project (MMP), a probability sample of PLWH receiving medical care; and the National HIV Surveillance System (NHSS), a surveillance system of all PLWH. Overall, data from 1,697 HOPS, 4,901 MMP, and 865,102 NHSS PLWH were analyzed. Compared with the MMP population, HOPS participants were more likely to be older, non-Hispanic/Latino white, not using injection drugs, insured, diagnosed with HIV before 2009, prescribed antiretroviral therapy, and to have most recent CD4+ T-lymphocyte cell count ≥500 cells/mm3 and most recent viral load test<2 00 copies/mL. The MMP population was demographically similar to all PLWH in NHSS, except it tended to be slightly older, HIV diagnosed more recently, and to have AIDS. Our comparative results provide an essential first step for combined epidemiologic data analyses to inform HIV care and prevention for PLWH in the US.

Is primary mycobacterium avium complex prophylaxis necessary in patients with CD4 <50 cells/µL who are virologically suppressed on cART?

We analyzed 369 patients with no prior Mycobacterium avium complex (MAC) infection and CD4 <50 cells/µL (baseline), while on combination antiretroviral therapy(cART), for incidence rates of primary MAC infection during the 6 months after baseline, by prophylaxis status. Of participants (median age, 40 years old), most were male (81%) and about half were non-white; at baseline, 81% of participants were on cART >60 days and 19% had HIV RNA <1000 copies/mL, whereas 65% had HIV RNA >10,000 copies/mL. Eleven patients had MAC infection within 6 months baseline (rate=0.6/100 person months): 4/175 on MAC prophylaxis vs. 7/194, no MAC prophylaxis (p=0.64). Of the 11 patients, seven had HIV RNA >10,000, and three >1000-9999 copies/mL at baseline (one missing). Median time to MAC infection was 62 days (IQR 43-126, maximum 139 days). No MAC infection occurred among 71 (19%) patients virologically suppressed (HIV RNA <1000 copies/mL) at baseline, including 41 patients with no MAC prophylaxis during follow-up. A small number of eligible virologically suppressed participants and the lack of data on cART/MAC prophylaxis adherence limited our observational nonrandomized study. Primary MAC prophylaxis may not be required for cART-virologically suppressed patients with CD4 <50 cells/mL.

Sexual risk behavior and viremia among men who have sex with men in the HIV Outpatient Study, United States, 2007-2010.

BACKGROUND: Recent US data on unsafe sexual behaviors among viremic HIV-infected men who have sex with men (MSM) are limited. METHOD: Using data abstracted from medical records of the participants in the HIV Outpatient Study (HOPS) and a supplemental behavioral survey, we assessed the frequency of high-risk sexual practices among HIV-infected MSM in care and examined the factors associated with risky sexual practices. We also compared the frequency of unprotected anal sex (UAS) with HIV-negative or unknown serostatus partners among viremic (HIV viral load ≥400 copies per milliliter) vs virologically suppressed (HIV viral load <400 copies per milliliter) MSM. RESULTS: Among 902 HIV-infected MSM surveyed, 704 (78%) reported having sex in the past 6 months, of whom 54% reported UAS (37% insertive, 42% receptive) and 40% UAS with a male partner who was HIV-negative or of unknown serostatus (24% insertive, 31% receptive). In multivariable regression with an outcome of engaging in any UAS with a male partner who was HIV-negative or of unknown serostatus, MSM aged <50 years, who reported injection drug use risk, had ≥2 sex partners, and who disclosed their HIV status to some but not to all of their sex partners were more likely to report this practice. Among MSM who reported any UAS, 15% were viremic; frequency of the UAS did not differ between viremic and virologically suppressed MSM. CONCLUSIONS: The high frequency of UAS with HIV-negative or unknown-status partners among HIV-infected MSM in care suggests the need for targeted prevention strategies for this population.

Trends in Decline of Antiretroviral Resistance among ARV-Experienced Patients in the HIV Outpatient Study: 1999-2008.

Background. Little is known about temporal trends in frequencies of clinically relevant ARV resistance mutations in HIV strains from U.S. patients undergoing genotypic testing (GT) in routine HIV care. Methods. We analyzed cumulative frequency of HIV resistance among patients in the HIV Outpatient Study (HOPS) who, during 1999-2008 and while prescribed antiretrovirals, underwent GT with plasma HIV RNA >1,000 copies/mL. Exposure ≥4 months to each of three major antiretroviral classes (NRTI, NNRTI and PI) was defined as triple-class exposure (TCE). Results. 906 patients contributed 1,570 GT results. The annual frequency of any major resistance mutations decreased during 1999-2008 (88% to 79%, P = 0.05). Resistance to PIs decreased among PI-exposed patients (71% to 46%, P = 0.010) as exposure to ritonavir-boosted PIs increased (6% to 81%, P < 0.001). Non-significant declines were observed in resistance to NRTIs among NRTI-exposed (82% to 67%), and triple-class-resistance among TCE patients (66% to 41%), but not to NNRTIs among NNRTI-exposed. Conclusions. HIV resistance was common but declined in HIV isolates from subgroups of ARV-experienced HOPS patients during 1999-2008. Resistance to PIs among PI-exposed patients decreased, possibly due to increased representation of patients whose only PI exposures were to boosted PIs.

Nitazoxanide and probiotics for the treatment of recurrent Clostridium difficile infection in a peritoneal dialysis patient.

Nitazoxanide has been proven to be efficacious for the treatment of Clostridium difficile infection (CDI), but data is limited in peritoneal dialysis (PD) patients. This report details the successful utilization of nitazoxanide and probiotics to treat multirecurrent CDI in a PD patient. A 58-year-old woman was admitted with hypotension, nausea and vomiting attributed to metronidazole therapy for CDI, her third CDI treatment regimen in 3 months. During her admission, the patient developed CDI and was started on a 6-week regimen of nitazoxanide and probiotics to assist in re-establishing the colonic flora. The regimen was well tolerated and the patient remained disease free at follow up, four months later.

Short-term safety and antiretroviral activity of T-1249, a second-generation fusion inhibitor of HIV.

T-1249 is a 39-aa synthetic peptide that inhibits fusion of human immunodeficiency virus (HIV) to the host target cell. A 14-day open-label, phase 1/2 dose-escalation monotherapy study of the safety and antiretroviral activity of T-1249 was performed on 115 HIV-1-infected adults. At baseline, the majority of the patients had advanced HIV disease (baseline median CD4(+) cell count, 57 cells/microL) and had extensive pretreatment (i.e., pre-T-1249) experience with antiretroviral medications (median, 11 antiretroviral drugs). Patients received T-1249 monotherapy by subcutaneous injection, for 14 days, at doses ranging from 6.25 to 192 mg/day. T-1249 was generally well tolerated, and no dose-limiting toxicity was identified. Injection-site reactions were the most commonly reported adverse event (57%). Dose-dependent decreases in plasma HIV-1 RNA load were observed; the median maximum change from baseline across dose groups ranged from -0.29 log(10) copies/mL (95% confidence interval [CI], -0.43 to -0.05 log(10) copies/mL) for the lowest dose to -1.96 log(10) copies/mL (95% CI, -2.02 to -1.37 copies/mL) for the highest dose. These results indicate that T-1249 is a potent new therapeutic agent for HIV-1 infection.

Once-daily versus twice-daily lopinavir/ritonavir in antiretroviral-naive HIV-positive patients: a 48-week randomized clinical trial.

The safety, pharmacokinetics, and antiviral activity of lopinavir, a human immunodeficiency virus (HIV) protease inhibitor, coformulated with ritonavir as a pharmacokinetic enhancer were evaluated in 38 antiretroviral-naive patients randomized 1:1 to receive open-label lopinavir/ritonavir at a dose of 800/200 mg once daily or 400/100 mg twice daily, each in combination with stavudine and lamivudine twice daily, for 48 weeks. Over the course of 48 weeks, median predose concentrations of lopinavir exceeded the protein-binding corrected concentration required to inhibit replication of wild-type HIV by 50% in vitro by 40- and 84-fold in the once- and twice-daily groups, respectively. Predose concentrations of lopinavir were more variable in the once-daily group (mean +/- SD, 3.62+/-3.38 microg/mL for the once-daily group and 7.13+/-2.93 microg/mL for the twice-daily group). At week 48, in an intent-to-treat (missing = failure) analysis, 74% of patients in the once-daily group and 79% of patients in the twice-daily group had HIV RNA levels of <50 copies/mL (P=.70). Study drug-related discontinuations occurred in 1 patient in each treatment group. Genotypic resistance testing of 4 patients with HIV RNA levels >400 copies/mL between weeks 24 and 48 demonstrated no protease inhibitor-resistance mutations.