The modern Russian pharmaceutical market: consumer attitudes towards distance retailing of medicines.

BACKGROUND: In Russia, remote retail trade of over-the-counter (OTC) medicines was legalised. According to statistics as of April 2020, consumer demand in the categories of "online pharmacies" increased by 803%. METHODS: The study was conducted in two stages by cross-sectional method using a structured questionnaire in the central region of Russia: 1st stage - July-August 2020; 2nd stage - February-March 2021. The results of the study were obtained using qualitative (method of discussions in focus groups) and quantitative methods (survey) of sociological research, logical and statistical analysis. The representativeness of the data was ensured by a sufficient sample size including 1194 consumers (with confidence probability = 0.95 and confidence interval ≤ 0.05). RESULTS: The number of respondents fully supporting the legalisation of online trade in medicines increased. Consumer attitudes towards online commerce depend on the age group of the respondents. 1.5 times more respondents over 46 years (12.1%) are strongly against distance selling of medicines compared to survey participants aged 18 to 25 years (7.8%). Six months after the first survey, no respondent strongly opposed the sale of prescription medicines through the internet, whereas in the first survey half of consumers held this view. The percentage of respondents who considered pharmaceutical counselling when purchasing medicines online as extremely important decreased by a factor of 4 over time (10.9%) M (08.2020) = 3.66 (0.992); M (03. 2021) = 3.17 (0.981) t = 7.66 (p < 0.05). Consumers consider accessibility for people with disabilities (80.3%) to be the most significant advantage of distance selling medicines. CONCLUSION: Consumer demand for the purchase of medicines online will grow as this type of sale has undeniable advantages. However, some risks remain when buying medicines online.

Hospitalization Rates and Outcomes Among Persons Living With Human Immunodeficiency Virus in the Southeastern United States, 1996-2016.

BACKGROUND: Antiretroviral therapy (ART) advances, aging, and comorbidities impact hospitalizations in human immunodeficiency virus (HIV)-positive populations. We examined temporal trends and patient characteristics associated with hospitalization rates and outcomes. METHODS: Among patients in the University of North Carolina Center for AIDS Research HIV Clinical Cohort receiving care during 1996-2016, we estimated annual hospitalization rates, time to inpatient mortality or live discharge, and 30-day readmission risk using bivariable Poisson, Fine-Gray, and log-binomial regression models. RESULTS: The 4323 included patients (29% women, 60% African American) contributed 30 007 person-years. Overall, the hospitalization rate per 100 person-years was 34.3 (95% confidence interval [CI], 32.4-36.4) with a mean annual change of -3% (95% CI, -4% to -2%). Patients who were black (vs white), older, had HIV RNA >400 copies/mL, or had CD4 count <200 cells/µL had higher hospitalization rates (all P < .05). Thirty-day readmission risk was 18.9% (95% CI, 17.7%-20.2%), stable over time (P > .05 for both 2010-2016 and 2003-2009 vs 1996-2002), and higher among black patients, those with detectable HIV RNA, and those with lower CD4 cell counts (all P < .05). Higher inpatient mortality was associated with older age and lower CD4 cell count (both P < .05). CONCLUSIONS: Hospitalization rates decreased from 1996 to 2016, but high readmissions persisted. Older patients, those of minority race/ethnicity, and those with uncontrolled HIV experienced higher rates and worse hospitalization outcomes. These findings underscore the importance of early ART and care engagement, particularly at hospital discharge.

Effectiveness of integrase strand transfer inhibitors among treatment-experienced patients in a clinical setting.

OBJECTIVE: Characterize virologic and immunologic outcomes of INSTI-based antiretroviral therapy (ART) in experienced patients with and without virologic failure. DESIGN: Prospective clinical cohort. METHODS: ART-experienced, INSTI-naive participants in the University of North Carolina Center for AIDS Research HIV Clinical Cohort (UCHCC) initiating an INSTI-containing regimen 2007-2016 were followed from INSTI initiation (baseline) to the earliest of: outcome of interest, loss to follow-up (LTFU, 1 year without clinical visit), or death. Outcomes of interest were virologic failure (first of two consecutive viral loads at least 200 copies/ml more than 2 weeks apart, or one viral load ≥200 before LTFU) and immune recovery (first CD4 ≥500 cells/µl). Patients with baseline viral load at least 50 copies/ml were given 24 weeks before meeting virologic failure criteria. Kaplan-Meier curves and Cox proportional hazards models compared INSTI regimens and patient characteristics. RESULTS: Of 773 patients, 32% were women, 59% African-American, and 42% had a viral load at least 50 copies/ml at INSTI initiation. After 2 years, 5% of patients with baseline viral load less than 50 copies/ml experienced virologic failure, compared with 35% of patients with baseline viral load at least 50 copies/ml (P < 0.01). Among patients with baseline viral load less than 50 copies/ml, dolutegravir/NRTIs was associated with longer time to virologic failure [adjusted hazard ratio (aHR) 0.11, 95% confidence interval (CI) 0.01-0.80], whereas among patients with baseline viral load at least 50 copies/ml, raltegravir/NRTIs was associated with longer time to virologic failure (aHR 0.35, 95% CI 0.18-0.68), both compared with elvitegravir/NRTIs. After 5 years suppressed, irrespective of baseline viral load, 61% of patients experienced immune recovery. CONCLUSION: In this cohort, INSTI-containing regimens led to low virologic failure rates in patients switching ART while suppressed. Viremic patients initiating INSTIs were at high risk of virologic failure during follow-up.

Medical and Social Factors of Pediculosis.

Pediculosis is a global problem in public health. An important factor in the efficient eradication of lice is ensuring adequate recognition and treatment of the disease by the population. In the present study, awareness of the population about the physiological properties of head lice, the ways of infestation with head lice, and the methods of treatment and prevention were studied. Perception of the disease by the people who had had head pediculosis and other people around them was identified.

Postpartum HIV care continuum outcomes in the southeastern USA.

OBJECTIVE: The aim of this study was to evaluate postpartum HIV care outcomes. DESIGN: A prospective clinical cohort of women with HIV and a live birth at the University of North Carolina, 1996-2014. METHODS: We estimated two stages of the HIV care continuum in the first 24 months postpartum: care retention (at least two visits per year, ≥90 days apart) and viral suppression (HIV RNA < 400 copies/ml). Multivariable models were fit using logistic regression. RESULTS: Among 1416 women, 141 experienced a live birth at a median age of 28 years, with 74% virally suppressed at delivery. Among all women, 48% were retained in care and 25% maintained viral suppression for the first 24 months postpartum. Among women with available HIV RNA measures, 42% were suppressed at 24 months. HIV care retention estimates were stable across calendar years, but viral suppression rates at 24 months postpartum, among women with available HIV RNA measures, increased from 33 to 67% from 1996-2001 to 2009-2014 (P = 0.04). Being at least 30 years old was positively, and receiving less than 12 weeks of antenatal antiretroviral therapy was negatively, associated with HIV care retention at 24 months postpartum [adjusted odds ratio (AOR): 2.41, 95% confidence interval (95% CI): 1.09-5.29 and AOR: 0.27, 95% CI: 0.08-0.86]. Older maternal age and viral suppression at delivery were both positively associated with virologic suppression at 24 months postpartum (AOR: 2.52, CI: 1.02-6.22, and AOR: 6.42 CI: 1.29-31.97, respectively). CONCLUSION: HIV care continuum outcomes decrease substantially postpartum, with younger women and those with less antenatal HIV care less likely to successfully remain engaged in HIV care following childbirth.

New antiretroviral agent use affects prevalence of HIV drug resistance in clinical care populations.

OBJECTIVE: To estimate the prevalence of HIV drug resistance over time and identify risk factors for multiclass resistance. DESIGN: Prospective clinical cohort of HIV-infected patients at the University of North Carolina. METHODS: Among antiretroviral therapy (ART)-experienced patients in care 2000-2016, we estimated annual prevalences of cumulative resistance, defined as at least one major mutation by drug class. Clinical data and multiple imputation were used when genotypic data were missing, and mutations were carried forward in time. We estimated resistance odds ratios comparing characteristics of patients in care in 2016. RESULTS: A total of 3682 patients contributed 23 169 person-years. Prevalence of at least one major resistance mutation, irrespective of viral suppression, peaked in 2005 with 49% (95% confidence interval 46, 52) and decreased to 38% (35, 40) in 2016. Resistance to nucleoside reverse transcriptase inhibitors, protease inhibitors, and nonnucleoside reverse transcriptase inhibitors also peaked in 2005-2007 and decreased to 28 (26, 31), 14 (12, 16), and 27% (24, 29) in 2016, respectively. In 2016, prevalence of integrase strand transfer inhibitor (INSTI) resistance was 2% (1, 3) and triple-class resistance 10% (9, 12). Over the study period, cumulative resistance was frequent among patients with detectable viremia, but uncommon among patients initiating ART post-2007. Among 1553 patients in care in 2016, ART initiation at an older age, with an INSTI, and with higher CD4 cell counts were associated with resistance to fewer or no classes. CONCLUSION: Prevalence of resistance to older ART classes has decreased in the last 10 years in this clinical cohort, whereas INSTI resistance has increased but remained very low. Patients with viremia continue to have a high burden of resistance even if they initiated ART recently.

Acute HIV Infection and CD4/CD8 Ratio Normalization After Antiretroviral Therapy Initiation.

BACKGROUND: We estimated the effect of initiating virologically suppressive antiretroviral therapy (ART) during acute HIV infection versus chronic HIV infection (AHI vs. CHI) on CD4/CD8 ratio normalization. SETTING: A prospective clinical cohort study. METHODS: We included patients initiating ART with AHI and CHI between 2000 and 2015 and compared time from ART initiation to the first normal CD4/CD8 ratio (defined as CD4/CD8 ≥1) using Kaplan-Meier curves and multivariable Cox proportional hazards models. Patient time was censored at virologic failure, lost to follow-up, or death. We also characterized CD4, CD8, and CD4/CD8 trajectories over the first 3 years of ART. RESULTS: The 1198 patients were 27% female and 60% African American, with a median age of 37 years (interquartile range 28-47) at ART initiation. The 83 AHI patients were more likely male, younger, and of white race, than CHI patients. After 2 years of suppressive ART, 70% of AHI patients achieved a normal CD4/CD8 ratio, compared to 6%-38% of CHI patients, with greater likelihood of normalization at higher baseline CD4 counts. Time to normalization was shortest among AHI patients, followed by CHI patients with higher baseline CD4. The adjusted hazard ratio for time to normalization for AHI patients compared to CHI patients with baseline CD4 >350 was 4.33 (95% CI: 3.16 to 5.93). Higher baseline CD4/CD8 ratio was also associated with time to normalization (adjusted hazard ratio 1.54; 1.46, 1.63, per 0.1 increase in ratio). CONCLUSIONS: Initiating ART during AHI at higher baseline CD4 cell counts and CD4/CD8 ratios was associated with shorter time to CD4/CD8 ratio normalization.

T cells establish and maintain CNS viral infection in HIV-infected humanized mice.

The human brain is an important site of HIV replication and persistence during antiretroviral therapy (ART). Direct evaluation of HIV infection in the brains of otherwise healthy individuals is not feasible; therefore, we performed a large-scale study of bone marrow/liver/thymus (BLT) humanized mice as an in vivo model to study HIV infection in the brain. Human immune cells, including CD4+ T cells and macrophages, were present throughout the BLT mouse brain. HIV DNA, HIV RNA, and/or p24+ cells were observed in the brains of HIV-infected animals, regardless of the HIV isolate used. HIV infection resulted in decreased numbers of CD4+ T cells, increased numbers of CD8+ T cells, and a decreased CD4+/CD8+ T cell ratio in the brain. Using humanized T cell-only mice (ToM), we demonstrated that T cells establish and maintain HIV infection of the brain in the complete absence of human myeloid cells. HIV infection of ToM resulted in CD4+ T cell depletion and a reduced CD4+/CD8+ T cell ratio. ART significantly reduced HIV levels in the BLT mouse brain, and the immune cell populations present were indistinguishable from those of uninfected controls, which demonstrated the effectiveness of ART in controlling HIV replication in the CNS and returning cellular homeostasis to a pre-HIV state.

Increased Persistence of Initial Treatment for HIV Infection With Modern Antiretroviral Therapy.

BACKGROUND: Initiating antiretroviral therapy (ART) early improves clinical outcomes and prevents transmission. Guidelines for first-line therapy have changed with the availability of newer ART agents. In this study, we compared persistence and virologic responses with initial ART according to the class of anchor agent used. SETTING: An observational clinical cohort study in the Southeastern United States. METHODS: All HIV-infected patients participating in the UNC Center for AIDS Research Clinical Cohort (UCHCC) and initiating ART between 1996 and 2014 were included. Separate time-to-event analyses with regimen discontinuation and virologic failure as outcomes were used, including Kaplan-Meier survival curves and adjusted Cox proportional hazards models. RESULTS: One thousand six hundred twenty-four patients were included (median age of 37 years at baseline, 28% women, 60% African American, and 28% white). Eleven percent initiated integrase strand transfer inhibitor (INSTI), 33% non-nucleoside reverse transcriptase inhibitor (NNRTI), 20% boosted protease inhibitor, 27% other, and 9% NRTI only regimens. Compared with NNRTI-containing regimens, INSTI-containing regimens had an adjusted hazard ratio of 0.49 (95% confidence interval, 0.35 to 0.69) for discontinuation and 0.70 (95% confidence interval, 0.46 to 1.06) for virologic failure. All other regimen types were associated with increased rates of discontinuation and failure compared with NNRTI. CONCLUSIONS: Initiating ART with an INSTI-containing regimen was associated with lower rates of regimen discontinuation and virologic failure.

Macrophages sustain HIV replication in vivo independently of T cells.

Macrophages have long been considered to contribute to HIV infection of the CNS; however, a recent study has contradicted this early work and suggests that myeloid cells are not an in vivo source of virus production. Here, we addressed the role of macrophages in HIV infection by first analyzing monocytes isolated from viremic patients and patients undergoing antiretroviral treatment. We were unable to find viral DNA or viral outgrowth in monocytes isolated from peripheral blood. To determine whether tissue macrophages are productively infected, we used 3 different but complementary humanized mouse models. Two of these models (bone marrow/liver/thymus [BLT] mice and T cell-only mice [ToM]) have been previously described, and the third model was generated by reconstituting immunodeficient mice with human CD34+ hematopoietic stem cells that were devoid of human T cells (myeloid-only mice [MoM]) to specifically evaluate HIV replication in this population. Using MoM, we demonstrated that macrophages can sustain HIV replication in the absence of T cells; HIV-infected macrophages are distributed in various tissues including the brain; replication-competent virus can be rescued ex vivo from infected macrophages; and infected macrophages can establish de novo infection. Together, these results demonstrate that macrophages represent a genuine target for HIV infection in vivo that can sustain and transmit infection.

Opportunities for sexual transmission of antiretroviral drug resistance among HIV-infected patients in care.

OBJECTIVE: To assess opportunities for transmitted drug resistance (TDR), we examined sexual risk behaviours, HIV viraemia and antiretroviral resistance among patients in care. DESIGN: A retrospective, cross-sectional analysis of clinical cohort data. METHODS: For 244 UNC Center for AIDS Research HIV Clinical Cohort participants, demographic and behavioural data were obtained during in-person interviews between 2000 and 2011. Genotypic resistance tests were interpreted using WHO surveillance drug resistance mutations (SDRMs). Log-linear binomial regression was used to evaluate associations with TDR risk, defined as unprotected sex in the prior 6 months, HIV RNA at least 400 copies/ml and at least one SDRM. RESULTS: Participants included 91 (37%) women and 153 men, of whom 92 (60%) were MSM. Median age was 43 years; 70% were Black (n = 171). Most (97%) were antiretroviral-experienced; 44% had exposure to more than four regimens. Among 204 individuals on antiretrovirals, 42% reported suboptimal adherence and 29% were viraemic. Over half of participants had at least one SDRM (n = 131); 26 (11%) had triple-class resistance. Overall, 70% were sexually active, and 55% used condoms inconsistently. Thirty (12%) reported unprotected sex during periods of drug-resistant viraemia. Higher TDR risk was associated with prior homelessness [adjusted prevalence ratio (aPR) 2.20, 95% confidence interval (CI) 1.16-4.18], active substance use (aPR 3.12, 95% CI 1.47-6.62) and nonsignificantly with MSM (aPR 1.75, 95% CI 0.93-3.28). CONCLUSION: A small but significant proportion of clinic patients with drug-resistant HIV engage in sexual behaviours that place others at risk for TDR. Targeted efforts in secondary prevention could have an impact on TDR incidence, over time.