HIV-1 Subtype D Infections among Caucasians from Northwestern Poland—Phylogenetic and Clinical Analysis

Background: HIV-1 subtype D infections, which are associated with a faster rate of progression and lymphocyte CD4 decline, cognitive deficit and higher mortality, have rarely been found in native Europeans. In Northwestern Poland, however, infections with this subtype had been identified. This study aimed to analyze the sequence and clinical data for patients with subtype D using molecular phylogeography and identify transmission clusters and ancestry, as well as drug resistance, baseline HIV tropism and antiretroviral treatment efficacy. Methods: Phylogenetic analyses of local HIV-1 subtype D sequences were performed, with time to the most recent common ancestor inferred using Bayesian modeling. Sequence and drug resistance data were linked with the clinical and epidemiological information. Results: Subtype D was found in 24 non-immigrant Caucasian, heterosexually infected patients (75 % of females, median age at diagnosis of 49.5 years; IQR: 29–56 years). Partial pol sequences clustered monophyletically with the clades of Ugandan origin and no evidence of transmission from other European countries was found. Time to the most common recent ancestor was 1989.24 (95 % HPD: 1968.83–1994.46). Baseline drug resistance to nucleoside reverse transcriptase inhibitors was observed in 54.5 % of cases (mutations: M41L, K103N, T215S/D) with evidence of clustering, no baseline integrase or protease resistance and infrequent non-R5 tropism (13.6%). Virologic failure was observed in 60 % of cases an

Serum leptin and adiponectin concentrations in patients infected with human immunodeficiency virus type 1 (HIV-1) on antiretroviral therapy

Efektem ubocznym skojarzonej terapii antyretrowirusowej (STA) jest zespół lipodystrofii z dyslipidemią oraz insulinoopornością. Cel pracy: określenie wpływu STA na stężenia leptyny i adiponektyny w powiązaniu ze zmianami poziomu lipidów krwi chorych zakażonych HIV leczonych antyretrowirusowo. U 56 chorych HIV(+) określono BMI i oznaczono we krwi stężenia leptyny, adiponektyny oraz triglicerydów, cholesterolu całkowitego, HDL- i LDL-cholesterolu przed oraz w trakcie STA, trwającej średnio 38,4 &plusmn; 13,2 miesięcy. Stwierdzono istotny (p = 0,0268) wzrost BMI (odpowiednio 22,6 &plusmn; 3,3 przed i 23,5 &plusmn; 3,4 kg/m2 po leczeniu) oraz analizowanych parametrów gospodarki lipidowej. Średnia stężeń adiponektyny u chorych leczonych była istotnie niższa (7,256 &plusmn; 3,551 &micro;g/ml) od średniej wartości sprzed rozpoczęcia terapii (8,395 &plusmn; 3,568 &micro;g/ml; p = 0,0011). Średnie stężeń leptyny nie różniły się istotnie (przed leczeniem 3,721 &plusmn; 0,347 log10; na leczeniu 3,1737 &plusmn; 0,353 log10). Zarówno przed, jak i w trakcie STA stwierdzono istotną, dodatnią korelację pomiędzy BMI a stężeniami leptyny (r = 0,5333; p < 0,0001), natomiast ujemną korelację pomiędzy stężeniami adiponektyny i leptyny (r = -0,2677; p = 0,042). Przed leczeniem nie wykazano istotnej korelacji pomiędzy stężeniami leptyny i adiponektyny w surowicy krwi a stężeniami lipidów. Stwierdzany w trakcie STA spadek stężenia adiponektyny korelował ujemnie z poziomami cholesterolu całkowitego (r = -0,2912; p = 0,0310) i LDL-cholesterolu (r = -0,310; p = 0,0225). STA trwająca ponad 2 lata spowodowała zmniejszenie stężenia adiponektyny, przy braku wpływu na stężenie leptyny u badanych chorych. Wzrost poziomu cholesterolu całkowitego i LDL-cholesterolu korelujący ze spadkiem stężenia adiponektyny potwierdza indukowanie przez STA zaburzeń metabolicznych zwiększających ryzyko rozwoju miażdżycy i jej następstw.The lipodystrophy syndrome with dyslipidaemia and insuline resistance is side-effect of combined antiretroviral therapy (CART). Aim of the study: to describe the influence of CART on leptin and adiponectin concentration in connection with lipids levels in HIV-infected patients on antiretroviral therapy.BMI, serum leptin, adiponectin, triglycerides, total cholesterol, HDL- and LDL-cholesterol concentrations were measured in 56 HIV(+) patients before and on CART; average of treatment duration 38.4 &plusmn; 13.2 months. Significant increase of BMI (p=0.0268) of (22.6 &plusmn; 3.3 before and 23.5 &plusmn; 3.4 kg/m2 on therapy, respectively) and all analyzed lipids were found. Mean adiponectin concentration in treated patients was significantly (7.256 &plusmn; 3.551 &micro;g/ml) lower than mean value before treatment (8.395 &plusmn; 3.568 &micro;g/ml; p=0.0011). Mean values of leptin concentrations did not differ significantly (before therapy 3.721 &plusmn; 0.347 log10; on therapy 3.1737 &plusmn; 0.353 log10). Significant positive correlation between BMI and leptin concentrations was found before, as well as during CART (r=0.5333;

Frequency of secondary drug resistance mutations in patients failing antiretroviral therapy.

<p>Frequency of secondary drug resistance mutations in patients failing antiretroviral therapy.</p

Relationships between the subtype D sequences inferred using maximum likelihood phylogeny (GenBank deposited <i>pol</i> sequences).

<p>Country-specific sequences are marked with the same color: red – Poland, blue – Uganda, green – Tanzania, yellow – Europe (except Poland), brown – Cameroon, magenta - Senegal, cyan- Sudan, dark green – other African countries, violet – South America, grey – Asia, orange – North America.</p

Phylogenetic trees of the subtype D sequences from Northwestern Poland.

<p>Figure a - maximum likelihood tree with bootstrap values for 1000 replicates drawn at the branches. Figure b – time scaled Bayesian MCMC tree. On the tree branches estimated time to the most recent common ancestor (tMRCA) and posterior probabilities expressed as percentage are shown. For both figures clustered sequences are marked in red and four identified clusters indicated as blue boxes and numbered are drawn on the right. Drug resistance mutations are marked at the tip nodes after the sequence identifier. *source patient for the transmission of the drug resistance within the cluster.</p

Frequency of baseline drug resistance mutations among treatment-naive patients.

<p>Frequency of baseline drug resistance mutations among treatment-naive patients.</p