Retrospective study on the outcome of two-drug regimens based on dolutegravir plus one reverse transcriptase inhibitor in virologically-suppressed HIV-infected patients.

This was a retrospective study on the efficacy and drug resistance mutations selected at virological failure (VF) in prospectively-followed HIV-infected patients switched to dolutegravir plus rilpivirine (DTG+RPV) or lamivudine (DTG+3TC) while virologically suppressed (HIV-RNA <50 copies/mL). VF was defined as HIV-RNA >50 copies/mL in two consecutive determinations or in a single determination if followed by treatment modification, or >1000 copies/mL in a single determination. Totally, 374 patients were analysed (307 switched to DTG+3TC and 67 to DTG+RPV); 220 had documented historical resistance. The median (IQR) time with HIV-RNA <50 copies/mL before switch was 4.52 (1.93-8.14) years. VF occurred in 17 patients after a median of 1.74 (0.90-2.46) years of follow-up in the 3TC group [incidence rate (95% CI) 3.34 (2.08-5.37) per 100-PYFU] and in 2 patients after a median of 1.78 (1.10-2.99) years of follow-up in the RPV group [incidence rate (95% CI) 1.57 (0.4-6.28) per 100-PYFU]. The 48-week estimated probabilities to maintain virological suppression during treatment with a two-drug regimen were 97.8% (95% CI 95.1-99.0%) vs. 98.3% (95% CI 88.6-99.8%) in the 3TC versus RPV group (P = 0.311). At switch, patients with VF had undetectable HIV-RNA since 0.71 (0.23-1.07) years versus 1.49 (0.64-2.2) years in those without VF (P = 0.001). In the 3TC group, VF was not associated with the presence of historical resistance to nucleoside analogues, and DTG-resistant variants were not selected at VF. One VF to DTG+RPV occurred because of historical resistance to RPV, accompanied by newly selected G140A and Q148R mutations. VF was infrequent with these regimens and was negatively associated with duration of viral undetectability. Drug resistance mutations selected at failure of these regimens were those expected in case of failure of any regimen including DTG, 3TC or RPV, but the impact of resistance to NRTIs on efficacy of DTG+3TC seems lower than expected.

Incidence and Predictors of Serological Treatment Response in Early and Late Syphilis Among People Living With HIV.

BACKGROUND: Few studies have investigated predictors of serological response to syphilis treatment in people living with HIV (PLWH). METHODS: This was a retrospective, longitudinal study on PLWH who were diagnosed with and treated for syphilis who had an assessable serological response between January 2004 and June 2016. Serological treatment response (TR) was defined as a ≥4-fold decline in rapid plasma reagin (RPR) titers or a reversion to nonreactive (if RPR ≤1:4 at diagnosis) 12 months after treatment for early syphilis and 24 months after treatment for late syphilis. Factors associated with a TR were assessed with multivariate Cox proportional hazard models for recurrent events. RESULTS: A total of 829 episodes of syphilis (686 early, 143 late) in 564 patients were recorded. TR was observed in 732 (88%) syphilis episodes. The proportion of TR differed between early and late syphilis (89% vs 83%, respectively; P = .045). For early syphilis, TR was associated with a higher nadir CD4+ cell count (adjusted hazard ratio [AHR], 1.06; P = .029), an RPR titer >1:32 at diagnosis (AHR, 1.26; P = .009), secondary syphilis (AHR, 1.29; P = .008), and cases of syphilis diagnosed in more recent calendar years (AHR, 1.36; P < .0001). In late syphilis, TR was more likely to occur for first infections (AHR, 1.80; P = .027), for episodes that occurred in more recent years (AHR, 1.62; P = .007), and for RPR titers >1:32 at diagnosis (AHR, 2.04; P = .002). TR was not associated with the type of treatment regimen in early and late syphilis. CONCLUSIONS: Higher RPR titers at diagnosis and a diagnosis of syphilis that was made in more recent years were associated with TR in early and late syphilis.

Brief Report: Hyperbilirubinemia Is Associated With a Decreased Risk of Carotid Atherosclerosis in HIV-Infected Patients on Virological Suppression.

OBJECTIVE: To investigate the association between total, direct, and indirect bilirubin and the presence of carotid lesions in a large sample of HIV-1-infected patients on virological suppression. DESIGN: Retrospective study on adult HIV-1-infected patients, with a carotid ultrasound (CUS) examination performed between January 2008 and August 2016, with HIV-RNA <50 copies per milliliter at CUS and without previous cardiovascular events. METHODS: Intima media thickness was measured in 4 segments: carotid common artery and bifurcation on the left and right sides. Carotid lesion was defined as an intima media thickness ≥1.5 mm in ≥1 region at CUS. Patients were classified as: normal if all bilirubin values before CUS were below the upper normal limit and with hyperbilirubinemia if ≥1 bilirubin value above upper normal limit before CUS was recorded. Multivariate logistic regression was used to determine whether hyperbilirubinemia showed association with the presence of ≥1 carotid lesion, after adjusting for confounding factors. RESULTS: Overall, 903 patients were evaluated, 511 with ≥1 and 392 without carotid lesions. At multivariate analysis, total [adjusted odds ratio (95% confidence interval) 0.57 (0.36 to 0.90), P = 0.016] and indirect hyperbilirubinemia before CUS [adjusted odds ratio (95% confidence interval) 0.62 (0.40 to 0.97), P = 0.036] were associated with a lower risk of carotid lesions in addition to younger age, negative hepatitis C virus antibodies, higher nadir CD4, lower low-density lipoprotein cholesterol, higher high-density lipoprotein cholesterol, lower triglycerides, and no use of statin; no effect of atazanavir treatment on carotid lesions was detected. CONCLUSIONS: In HIV-1-treated patients, total or indirect hyperbilirubinemia was likely associated with the absence of carotid lesions.

Efficacy and safety in clinical practice of a rilpivirine, tenofovir and emtricitabine single-tablet regimen in virologically suppressed HIV-positive patients on stable antiretroviral therapy.

INTRODUCTION: Switching to a rilpivirine, tenofovir and emtricitabine (RTE) single-tablet regimen (STR) has been evaluated in a limited number of virologically suppressed patients. The aim of this study was to describe clinical outcomes in HIV-positive patients switched from a suppressive antiretroviral regimen to RTE STR in routine clinical practice. METHODS: In this retrospective study of antiretroviral-treated patients with <50 copies of HIV RNA/mL switched to RTE STR, virological failure (VF) was defined as two consecutive measurements of ≥50 copies/mL or a single measurement of ≥50 copies/mL followed by any change in treatment. Treatment failure (TF) was defined as VF or discontinuation of the STR for any reason. Univariate mixed-linear models were used to identify differences in laboratory parameters over time. RESULTS AND DISCUSSION: The analysis involved 307 patients (83% males) with a median age of 45.8 years (interquartile range (IQR 39.3-50.9), who were followed up for a median of 7.4 months (IQR 4.6-10.9). VF occurred in three patients (1%) switched from a protease inhibitor (PI)-based regimen, after a median of 2.6 months (IQR 1.6-3.0), and TF in 34 patients (11%) after a median of three months (IQR 1.4-5.8), 24 of whom (71%) were receiving a PI-based regimen at baseline. Overall, there was a slight but statistically significant improvement in the mean monthly change from baseline in CD4+ cell counts (p=0.027), the CD4+/CD8+ ratio (p=0.0001), and Hb (p=0.024), alanine amino transferase (ALT) (p=0.009), total bilirubin (p<0.0001), indirect bilirubin (p<0.0001), total cholesterol (p<0.0001) and triglyceride (p<0.0001) levels. There was also a slight but statistically significant increase in serum creatinine (p=0.0004), aspartate amino transferase (AST) (p=0.001) and liver fibrosis index (FIB-4) (p=0.002), and a decrease in eGFRcreat (p<0.0001) and high-density lipoprotein (HDL) cholesterol (p<0.0001) values. The study limitations include its retrospective design, the relatively short follow-up, and the absence of data concerning the severity of clinical adverse events; however, it does provide new information concerning the laboratory changes that occur in patients switching from PI-based or PI-sparing regimens to RTE STR. CONCLUSIONS: The study findings confirm the efficacy and safety in clinical practice of switching to RTE STR in virologically suppressed patients receiving other antiretrovirals.

Predictors of lack of serological response to syphilis treatment in HIV-infected subjects.

INTRODUCTION: The aim of this study was to determine factors associated with lack of serological response (LSR) to treatment of syphilis among HIV-infected subjects. MATERIALS AND METHODS: Retrospective, longitudinal study on HIV-infected subjects diagnosed and treated for syphilis and with an assessable serological response between 1 January 2004 and 15 September 2013. LSR was defined as a <4-fold decline of rapid plasma reagin (RPR) titer or a failed reversion to nonreactive (if RPR ≤1:4 at diagnosis) after one year since treatment. Diagnoses of syphilis were staged in early syphilis (primary, secondary and early latent) or late syphilis (tertiary and late latent) according to clinical examination and patient's history. Syphilis was classified in new infections [NI: positive RPR and TPHA (Treponema pallidum Haemagglutination assay) titers in subjects without previous history of syphilis] or re-infections [ReI: a ≥4-fold increase of RPR titer in subjects previously successfully treated for syphilis]. Syphilis treatment was prescribed according to CDC guidelines. The crude incidence rates (IRs) of LSR were calculated per 1000-person months of follow-up (PMFU) as the total number of LSR episodes divided by the cumulative time contributed by all subjects (interval time since each syphilis diagnosis and the date of ascertainment of response). RESULTS are described as median (IQR) or frequency (%). RESULTS: 565 diagnoses of syphilis with an assessable serological response in 421 patients; 458 (81%) were early syphilis, 189 (33%) were NI, 376 (67%) were ReI. At first, diagnosis of syphilis median age was 41 (36-47) years, 419 (99.5%) males, 391 (93%) MSM, HIV-infected since 7.7 (3.5-12.9) years, 75 (18%) HCV or HBV co-infected, 56 (13%) with a previous AIDS diagnosis, 82 (19%) antiretroviral treatment naïve, 102 (24%) with HIV-RNA ≥50 cp/mL, CD4+=576 (437-749) cells/mm(3), nadir CD4+=308 (194-406) cells/mm(3). LSRs were observed in 70/565 (12.4%) treated syphilis. Incidence of LSR decreased over time [2004-2008 IR=25.1 (17.2-33.1)/1000 PMFU; 2009-2010 IR=21.1 (12.3-29.9)/1000 PMFU; 2011-2013 IR=10.6 (5.1-18.2)/1000 PMFU; Poisson regression: p=0.001]. RESULTS of univariate and multivariate analysis on the risk of LSR are reported in Table 1. CONCLUSIONS: In HIV-infected subjects we observed 12% of LSR to treatment of syphilis. LSR was associated with an older age, late syphilis, lower nadir CD4+ and detectable HIV viral load.

Leishmania infection can hamper immune recovery in virologically suppressed HIV-infected patients.

An HIV-infected patient started combination antiretroviral therapy with 13 CD4+ cells/microL. Despite sustained virological suppression over the following four years, the anemia did not resolve, and the CD4+ cell counts always remained below 200/microL until co-infection with Leishmania was diagnosed in October 2006 when the patient started complaining of persistent mild fever and asthenia. Once treatment for leishmaniasis was started with miltefosine, CD4+ cell count rose above 400/microL. A new drop in CD4+ cell count was observed when Leishmania DNA turned out again to be positive, but treatment with liposomal amphotericin-B restored immune recovery.

In vivo dynamics of the K103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors in Human Immunodeficiency Virus-infected patients.

To investigate the dynamics of the K103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors (NNRTIs), we selected the Human Immunodeficiency Virus (HIV)-infected patients with the mutation at the time or after the failure of an NNRTI-containing regimen from an observational database. Of 62 patients fulfilling the inclusion criteria, 39 continued antiretroviral treatment without NNRTIs (group A), whereas 23 discontinued all antiretrovirals after NNRTI failure (group B). A total of 149 tests were analysed, with a median (IQR) of two (2-3) tests/patient. The overgrowth of wild-type virus at position 103 was observed in 14 subjects in group A (36%) and nine in group B (39%). No significant trend was found in relation to the disappearance of K103N variants in either group, but patients tested while receiving antiretrovirals had a significantly higher probability of retaining the K103N mutation over 24 months than those tested during treatment interruption (P = 0.007). In conclusion, following NNRTI discontinuation, HIV variants carrying the K103N mutation are not overgrown for long by wild-type quasispecies at this position in the majority of patients, although treatment interruption favours their disappearance. This suggests that the K103N mutation per se has little impact on viral fitness in vivo.