Ikumi Genka

Anti-HIV Effect of Saquinavir Combined with Ritonavir Is Limited by Previous Long-Term Therapy with Protease Inhibitors

Combination therapy of saquinavir (SQV) and ritonavir (RTV) seems to have a strong antiretroviral effect pharmacokinetically. The purpose of this study was to examine the effectiveness of combined therapy using SQV and RTV in patients previously treated with protease inhibitors (PIs) and to identify the factors compromising the response to such combination therapy. Nineteen HIV-infected Japanese patients participated in this trial between June 1997 and July 1998, and were monitored until November 1998. Patients were treated with SQV (400 mg twice daily) and RTV (300 or 400 mg twice daily). Among the 17 patients who continued such therapy for longer than 3 months, 6 were responders. Among nonresponders, the duration of PI therapy was longer and a higher frequency of preexisting PI resistance viral mutations was detected than in responders. No significant differences were found in previous use of reverse transcriptase inhibitor therapy, CD4+ and CD8+ T cell counts, viral load at baseline, and plasma concentrations of SQV and RTV between responders and nonresponders. Our results suggest that the response to SQV combined with RTV therapy is complicated by previous long-term treatment with PIs, probably owing to multiple PI resistance mutations. Even in patients with a PI-sensitive HIV genotype, however, resistance mutations can develop during therapy and abrogate the effect of high plasma SQV concentrations.

Serious Bradyarrhythmia That Was Possibly Induced by Lopinavir-Ritonavir in 2 Patients with Acquired Immunodeficiency Syndrome

We describe 2 patients with acquired immunodeficiency syndrome who had potentially fatal bradyarrhythmia that occurred shortly after commencement of antiretroviral therapy. Lopinavir-ritonavir was the only drug that both patients were using.

Sustained Cytomegalovirus-Specific CD4+ T Cell Response Associated with Prevention of Recurrence of Cytomegalovirus Retinitis without Secondary Prophylaxis after Highly Active Antiretroviral Therapy in Patients with AIDS

It has been demonstrated that the cytomegalovirus (CMV)-specific CD4(+) T cell response could be restored after ganciclovir and highly active antiretroviral therapy (HAART) in AIDS patients. In this study, we first confirmed the above observation cross-sectionally. We then performed a prospective longitudinal study over a period of 48 weeks. The second study included nine patients. All patients had received HAART. Five patients had a history of retinitis that was, however, under control after discontinuation of anti-CMV therapy more than 1 year before this study (group A). The other four had active CMV retinitis at the start of this study and anti-CMV therapy was required to control retinitis (group B). Median periods between commencement of HAART and the start of this study in group A and in group B were 27 and 4.5 months, respectively. Within both groups, the number of CD4(+) T cells that produced tumor necrosis factor alpha in response to CMV antigen did not vary throughout the observation period (Friedman test; p > 0.05). However, the median number of responsive CD4(+) T cells in group A patients was significantly higher than in group B (p < 0.05). Our results demonstrate that the number of CMV-responsive CD4(+) T cells increased when HIV was well controlled with HAART and was then maintained, and suggest that these cells may play an important role in the control of retinitis in patients with AIDS.

Primary nelfinavir (NFV)-associated resistance mutations during a follow-up period of 108 weeks in protease inhibitor naı̈ve patients treated with NFV-containing regimens in an HIV clinic cohort

BACKGROUND Nelfinavir (NFV) is a widely prescribed HIV-1 specific protease inhibitor (PI). However, there are only a few reports that have described the long-term effects of NFV-containing regimens, especially with regard to the emergence of drug resistance in inner-city clinics. OBJECTIVES The aim of this study was to investigate the clinical and virologic responses to treatment with NFV-containing regimens for up to 108 weeks and determine the timing and rate of emergence of primary NFV-resistance associated mutations in daily clinical practice. STUDY DESIGN A cohort study in an inner-city clinic. Our study included 51 consecutive patients who were PI-nai;ve and commenced therapy in February 1997 through April 1999. RESULTS AND CONCLUSIONS The proportions of patients who continued the same therapeutic regimen and showed virologic success (viral load <400 copies/ml) up to 108 weeks were 78 and 63%, respectively, based on intent-to-treat analysis. Among patients with a viral load persistently >400 copies/ml at week 12 (n=30), 11 developed primary NFV-resistance associated mutations by 108 weeks (stratified log-rank test; P<0.05). The Cox proportional hazard model showed that prior use of reverse transcriptase inhibitors (n=22) (relative hazard (RH); 2.10, 95% CI; 0.67-6.62), prior AIDS diagnosis (n=6) (RH; 1.70, 95% CI; 0.37-7.77), CD4 < 200/microl at baseline (n=19) (RH; 2.48, 95% CI; 0.78-7.81) and viral load >30,000 copies/ml at baseline (n=21) (RH; 2.10, 95% CI; 0.67-6.62) were not independent predictors of the NFV-resistance, although some tendency was noted. In total, 77% of the patients continued NFV-containing treatment without the NFV-resistance for 108 weeks. The viral load at week 12 could be used as a predictor of treatment success in our cohort study.

Incidence and Risk Factors for Incident Syphilis among HIV-1-Infected Men Who Have Sex with Men in a Large Urban HIV Clinic in Tokyo, 2008−2015

Background The epidemiology of incident syphilis infection among HIV-1-infected men who have sex with men (MSM) largely remains unknown. Methods The incidence and risk factors for incident syphilis (positive TPHA and RPR> = 1:8) among HIV-1-infected MSM who visited a large HIV clinic in Tokyo for the first time between 2008 and 2013 were determined, using clinical data and stored blood samples taken every three months for screening and determination of the date of incident syphilis. Poisson regression compared the incidence of syphilis at different observation periods. Results Of 885 HIV-1-infected MSM with baseline data, 34% either presented with active syphilis at baseline (21%) or became infected with syphilis during follow-up (13%). After excluding 214 patients (MSM with syphilis at baseline (n = 190) and no follow-up syphilis test (n = 24)), of 671 men, 112 (17%) developed incident syphilis with an incidence of 43.7/1,000 person-years [95% CI, 36.5–52.3]. The incidence decreased slightly during observation period although the trend was not significant (2008–2009: 48.2/1,000 person-years, 2010–2011: 51.1/1,000 person-years, 2012–2013: 42.6/1,000 person-years, 2014 to 2015: 37.9/1,000 person-years, p = 0.315). Multivariable analysis identified young age (<33 years versus >40, HR 4.0, 95%CI 2.22–7.18, p<0.001), history of syphilis at baseline (HR 3.0, 95%CI 2.03–4.47, p<0.001), positive anti-amoeba antibody (HR 1.8, 95%CI 1.17–2.68, p = 0.006), and high baseline CD4 count (CD4 ≥350 /μL versus CD4 <200, HR 1.6, 95%CI 1.00–2.53, p = 0.050) as risk factors for incident syphilis. Incidence of syphilis was particularly high among young patients (age <33 years: 60.1/1,000 person-years). Interestingly, 37% of patients with incident syphilis were asymptomatic. Conclusions Although incidence of syphilis did not increase during the observation period, it was high among HIV-1-infected MSM, especially among young HIV-1-infected MSM and those with history of syphilis, in Tokyo. Regular screening for syphilis needs to be strictly applied to this population.