Transmitted drug-resistance (TDR) remains a critical aspect for the management of HIV-1-infected individuals. Thus, studying the dynamics of TDR is crucial to optimize HIV care. In total, 4323 HIV-1 protease/reverse-transcriptase sequences from drug-naive individuals diagnosed in north and central Italy between 2000 and 2014 were analysed. TDR was evaluated over time. Maximum-likelihood and Bayesian phylogenetic trees with bootstrap and Bayesian-probability supports defined transmission clusters. Most individuals were males (80.2%) and Italian (72.1%), with a median (IQR) age of 37 (30–45) years. MSM accounted for 42.2% of cases, followed by heterosexuals (36.4%). Non-B subtype infections accounted for 30.8% of the overall population and increased over time (<2005–14: 19.5%–38.5%, P < 0.0001), particularly among Italians (<2005–14: 6.5%–28.8%, P < 0.0001). TDR prevalence was 8.8% and increased over time in non-B subtypes (<2005–14: 2%–7.1%, P = 0.018). Overall, 467 transmission clusters (involving 1207 individuals; 27.9%) were identified. The prevalence of individuals grouping in transmission clusters increased over time in both B (<2005–14: 12.9%–33.5%, P = 0.001) and non-B subtypes (<2005–14: 18.4%–41.9%, P = 0.006). TDR transmission clusters were 13.3% within the overall cluster observed and dramatically increased in recent years (<2005–14: 14.3%–35.5%, P = 0.005). This recent increase was mainly due to non-B subtype-infected individuals, who were also more frequently involved in large transmission clusters than those infected with a B subtype [median number of individuals in transmission clusters: 7 (IQR 6–19) versus 4 (3–4), P = 0.047]. The epidemiology of HIV transmission changed greatly over time; the increasing number of transmission clusters (sometimes with drug resistance) shows that detection and proper treatment of the multi-transmitters is a major target for controlling HIV spread.
article: Classical Kaposi’s sarcoma concurrent with ledipasvir-sofosbuvir therapy for hepatitis C infection - Giornale Italiano di Dermatologia e Venereologia 2019 October;154(5):593-4 - Minerva Medica - Journals
Lamivudine was demonstrated to be a potent inhibitor of hepatitis B virus (HBV) replication [1]. Since the first quarter of the year 2000, lamivudine has been approved for use in Italy in patients with chronic hepatitis B with evidence of HBV replication and inflammatory liver disease. However, approval for the use of lamivudine in chronic hepatitis B came approximately 3 years after its approval for use in combination therapy in HIV-infected patients, so that many HIV/HBV co-infected patients had used it before its approval for hepatitis B. Studies have also demonstrated the effectiveness of lamivudine in HBV/HIV co-infected patients reporting suppression of HBV-DNA concentrations in up to 90% of patients [2,3]. Moreover, the discontinuation of lamivudine in HIV/HBV co-infected patients may cause an increase in HBV-DNA and transaminase levels [4]. Case report A 28-year-old woman, married since 1993 to a hepatitis B serum antigen-positive man (first test performed in 1992) came to our attention in June 1998, when she was in the 24th week of pregnancy and was found to be anti-HIV-positive for the first time. She reported only one sexual partner in her lifetime: her husband. Although she had been advised to undergo HBV vaccination, she had always refused. The husband’s HBV marker pattern at that time was as follows: anti-hepatitis serum negative, hepatitis B e antigen negative, anti-hepatitis B e positive, hepatitis B core antigen (HBcAg)/IgM negative, HBcAg total IgG positive, HBV-DNA negative (lower limit of detection: 0.5 pg/ml blood); he was also anti-hepatitis C virus positive, but had normal transaminase levels. After the wife’s test, he also underwent HIV testing and was found to be positive: his first CD4 lymphocyte count was 27 cells/mm3 and HIV-RNA level was 150 000 copies/ml. He reported multiple sexual intercourse, including with prostitutes, before his marriage. He started antiretroviral therapy including stavudine, lamivudine and saquinavir, switched to stavudine, lamivudine and nevirapine in March 2000, and subsequently experienced a slow but progressive increase in his CD4 lymphocyte count, which reached 228 cells/mm3 in July 2000. He was routinely checked for HBV markers and transaminase levels, and neither value showed significant changes during that time. The first CD4 cell count of the female patient was 300 cells/mm3 and HIV-RNA level was 100 000 copies/ml. She started antiretroviral therapy with two drugs: zidovudine and lamivudine during pregnancy and saquinavir-hard gel was added after the delivery in October 1998. In March 2000, with a CD4 cell count of 600 cells/mm3 and HIV-RNA level of 270 copies/ml, she switched to zidovudine, lamivudine and nevirapine, but stopped the whole therapy after 10 days because of a skin rash; at that time she had negative HBV markers. The patient still refused to undergo HBV vaccination. In May 2000, she started a new therapy including zidovudine, lamivudine and efavirenz, which was also stopped after 7 days because of a rash. In June 2000, she underwent a genotypic resistance test for HIV, showing a complete resistance pattern to the protease inhibitors, didanosine and lamivudine. As a result of intolerance to non-nucleoside reverse transcriptase inhibitors, such as nevirapine and efavirenz, and in the absence of a valid regimen of combination treatment, the patient remained without HIV therapy. Her CD4 lymphocyte count was 484 cells/mm3 and HIV-RNA level was 18 000 copies/ml at that time. In August 2000, the patient developed acute hepatitis, with a bilirubin level of 12.1 mg/100 ml and an alanine aminotransferase level of 2276 mg/100 ml. The husband’s HBV-DNA level was still negative. The patient’s HBV marker pattern was as follows: hepatitis B serum antigen positive, anti-hepatitis B serum negative, hepatitis B e antigen positive, anti-hepatitis B e negative, HBcAg/IgM positive, HBcAg total IgG negative, HBV DNA negative. The patient was still anti-hepatitis C virus negative. This pattern was confirmed in September, although the alanine aminotransferase level returned to nearly normal values (71 mg/100 ml). The CD4 cell count was 357 cells/mm3 and the HIV-RNA level was 27 000 copies/ml. The onset of acute hepatitis B was at well-matched time after the interruption of lamivudine. Considering that the patient reported unprotected sex with her husband during this period and that the infection occurred as soon as lamivudine was stopped, the hypothesis that, in this case, lamivudine might play a role in the prevention of hepatitis B at least in the past 2 years is attractive, although the routine use of the drug in similar situations needs investigational confirmation. Giuseppina Liuzzi Mauro Zaccarelli Pietro Sette Susanna Grisetti Lucia Alba Andrea Antinori
In recent years, increasing numbers of patients infected with HIV-1 non-B subtypes have been treated with modern antiretroviral regimens. Therefore, a better knowledge of HIV drug resistance in non-B strains is crucial. Thus, we compared the mutational pathways involved in drug resistance among the most common non-B subtypes in Italy (F, C, and CRF02_AG) and the B subtype. In total, 2234 pol sequences from 1231 virologically failing patients from Central Italy were analyzed. The prevalence of resistance mutations in protease and reverse transcriptase between non-B and B subtypes has been evaluated. Among patients treated with nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) and with thymidine analogues (TA) experience, TAMs1 M41L and L210W were less prevalent in CRF02_AG, while TAMs2 T215F and K219E were more prevalent in the F subtype. In NRTI-treated patients having experience with abacavir, didanosine, tenofovir, or stavudine the K65R mutation was mostly prevalent in the C subtype. In non-NRTI (NNRTI)-treated patients infected by the C subtype the prevalence of K103N was lower than in patients infected with other subtypes, while the prevalence of Y181C and Y188L was higher compared to subtype B. The prevalence of Y181C was higher also in subtype F as compared to subtype B. In patients treated with protease inhibitors, L89V was predominantly found in CRF02_AG, while the TPV resistance mutation T74P was predominantly found in the C subtype. Some differences in the genotypic drug resistance have been found among patients infected with B, C, F, and CRF02_AG subtypes in relationship to treatment. These results may be useful for the therapeutic management of individuals infected with HIV-1 non-B strains.
AbstractBackground: Few published studies have considered both the short- and long-term virologic or immunologic response to combination antiretroviral therapy (cART) and the impact of different cART strategies. Purpose: To compare time to initial virologic (<500 copies/mL) or immunologic (>200/mm3 cell increase) response in antiretroviral-naïve patients starting either a single protease inhibitor (PI; n = 183), a ritonavir-boosted PI regimen (&n = 197), or a nonnucleoside reverse transcriptase inhibitor (NNRTI)–based cART regimen (n = 447) after January 1, 2000, and the odds of lack of virologic or immunologic response at 3 years after starting cART. Method: Cox proportional hazards models and logistic regression. Results: After adjustment, compared to patients taking an NNRTI-regimen, patients taking a single-PI regimen were significantly less likely to achieve a viral load (VL) <500 copies/mL (relative hazard [RH] 0.74, 95% CI 0.54–0.84, p = .0005); there was no difference between the boosted-PI regimen and the NNRTI regimen (p = .72). There were no differences between regimens in the risk of >200/mm3 CD4 cell increase after starting cART (p > .3). At 3 years after starting cART, patients taking a single-PI–based regimen were more likely to not have virologic suppression (<500 copies/mL; odds ratio [OR] 1.60, 95% CI 1.06–2.40, p = .024), while there were no differences in the odds of having an immunologic response (>200/mm3 increase; p > .15). This model was adjusted for CD4 and VL at starting cART, age, prior AIDS diagnosis, year of starting cART, and region of Europe. Conclusion: Compared to patients starting an NNRTI-based regimen, patients starting a single-PI regimen were less likely to be virologically suppressed at 3 years after starting cART. These results should be interpreted with caution, because of the potential biases associated with observational studies. Ultimately, clinical outcomes, such as new AIDS diagnoses or deaths, will be the measure of efficacy of cART regimens, which requires the follow-up of a very large number of patients over many years.Keywords: combination therapyimmunologic successvirologic success
Hepatitis E is generally considered a mild disease, but severe cases are also observed. In high-income countries, most hepatitis E cases are due to HEV genotype 3 and are linked mainly to the consumption of pork or wild boar meat, but data on the correlation of viral variants and hepatitis severity are still preliminary. We described a serious acute hepatitis E (Genotype 3e) case observed in the city of Rieti (Lazio region, Italy), and compared it with previous cases found in the same geographical area. Phylogenetic analysis of open reading frame 2 (ORF2) showed that the HEV strain of the patient in Rieti is closely related to those identified in the acute HEV hepatitis outbreak in 2019. Our data suggest the need to strengthen surveillance and prevention against HEV infection and investigation of pathogenicity linked to specific HEV variants.
In this study we evaluated the level of HIV RNA in plasma and HIV DNA in peripheral blood cells. Sixteen antiretroviral-experienced HIV patients with severe immune suppression were included in the study. After the first month, 56.2% of the patients showed undetectable levels of HIV RNA, this percentage remaining stable after 1 year (53.3%). At enrollment, 7 patients (43.7%) with a low CD4+T cell count (mean 22 per mm3 versus 73) showed HIV DNA levels below the limit of detection (5 copies/105) in lymphocytes. They all subsequently had increased HIV DNA that became detectable between the first and the third month of therapy, associated with an increase of the CD4+T cell count (mean 22 to 95 / mm3); in 4 of these patients this increase was transitory, becoming undetectable again after one year. In 7 out of the 8 patients with detectable HIV DNA at enrollment, the HIV DNA level decreased over time. Seven out of 15 patients at 1 year (46.7%) showed both undetectable levels of HIV RNA in plasma and HIV DNA in lymphocytes (p<0.05); these patients had a higher CD4+T cell count at baseline (mean 75 versus 25 / mm3) and a higher increase (306 versus 177 / mm3) after 1 year. PCR-based dilution assay carried out at 1 year showed that all patients had a consistent amount of HIV DNA positive- CD4+T lymphocytes and macrophages, with higher values in these last cells.The data indicate that a durable reservoir of virus is still present in both lymphocytes and monocytes, even after long-lasting HAART treatment.
The increasing incidence of human immunodeficiency virus (HIV) infection in women of childbearing age led us to evaluate whether pregnancy affects the natural history of this disease.To conduct a prospective study of women with known dates of HIV seroconversion to describe the incidence and outcome of pregnancy and to assess differences according to age and exposure group. To compare the rate of disease progression between pregnant and nonpregnant women.All participants, recruited from 14 clinical centers in Italy, had documented HIV-seronegative test results followed by confirmed positive test results within 2 years.A total of 331 women, who had seroconversion between 1981 and 1994, were followed up for a median of 5.5 years from seroconversion; 94 developed HIV-related diseases, 47 developed acquired immunodeficiency syndrome, and 53 had at least 1 CD4 cell count lower than 0.10 x 10(9)/L (< 100 cells/mm3). Thirty-eight women (11.5%) were pregnant at the time of HIV seroconversion and 31 (9.4%) became pregnant after HIV seroconversion (cumulative incidence of pregnancy within 8 years of seroconversion, 28.9%; 95% confidence interval, 21.6%-36.2%). Forty-five (65.2%) of the 69 pregnancies were carried to term. There were no discernible differences in these findings by age or exposure group. Pregnant women did not experience a more rapid rate of progression of disease, even when adjusting for age, exposure group, CD4 cell count, or use of treatment (adjusted relative hazards: HIV-related diseases, 0.72; acquired immunodeficiency syndrome, 0.69; CD4 cell count <0.10 x 10(9)/L, 1.24).Women infected with HIV continue to become pregnant after seroconversion, yet pregnancy does not appear to influence the rate of progression of HIV disease.
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