Efavirenz versus boosted atazanavir-containing regimens and immunologic, virologic, and clinical outcomes: A prospective study of HIV-positive individuals.

OBJECTIVE: To compare regimens consisting of either ritonavir-boosted atazanavir or efavirenz and a nucleoside reverse transcriptase inhibitor (NRTI) backbone with respect to clinical, immunologic, and virologic outcomes. DESIGN: Prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States included in the HIV-CAUSAL Collaboration. METHODS: HIV-positive, antiretroviral therapy-naive, and acquired immune deficiency syndrome (AIDS)-free individuals were followed from the time they started an atazanavir or efavirenz regimen. We estimated an analog of the "intention-to-treat" effect for efavirenz versus atazanavir regimens on clinical, immunologic, and virologic outcomes with adjustment via inverse probability weighting for time-varying covariates. RESULTS: A total of 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths) and 18,786 individuals started an efavirenz regimen (389 deaths, 825 AIDS-defining illnesses or deaths). During a median follow-up of 31 months, the hazard ratios (95% confidence intervals) were 0.98 (0.77, 1.24) for death and 1.09 (0.91, 1.30) for AIDS-defining illness or death comparing efavirenz with atazanavir regimens. The 5-year survival difference was 0.1% (95% confidence interval: -0.7%, 0.8%) and the AIDS-free survival difference was -0.3% (-1.2%, 0.6%). After 12 months, the mean change in CD4 cell count was 20.8 (95% confidence interval: 13.9, 27.8) cells/mm lower and the risk of virologic failure was 20% (14%, 26%) lower in the efavirenz regimens. CONCLUSION: Our estimates are consistent with a smaller 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with atazanavir regimens. No overall differences could be detected with respect to 5-year survival or AIDS-free survival.

Boosted lopinavir- versus boosted atazanavir-containing regimens and immunologic, virologic, and clinical outcomes: a prospective study of HIV-infected individuals in high-income countries.

BACKGROUND: Current clinical guidelines consider regimens consisting of either ritonavir-boosted atazanavir or ritonavir-boosted lopinavir and a nucleoside reverse transcriptase inhibitor (NRTI) backbone among their recommended and alternative first-line antiretroviral regimens. However, these guidelines are based on limited evidence from randomized clinical trials and clinical experience. METHODS: We compared these regimens with respect to clinical, immunologic, and virologic outcomes using data from prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States in the HIV-CAUSAL Collaboration, 2004-2013. Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started a lopinavir or an atazanavir regimen. We estimated the 'intention-to-treat' effect for atazanavir vs lopinavir regimens on each of the outcomes. RESULTS: A total of 6668 individuals started a lopinavir regimen (213 deaths, 457 AIDS-defining illnesses or deaths), and 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths). The adjusted intention-to-treat hazard ratios for atazanavir vs lopinavir regimens were 0.70 (95% confidence interval [CI], .53-.91) for death, 0.67 (95% CI, .55-.82) for AIDS-defining illness or death, and 0.91 (95% CI, .84-.99) for virologic failure at 12 months. The mean 12-month increase in CD4 count was 8.15 (95% CI, -.13 to 16.43) cells/µL higher in the atazanavir group. Estimates differed by NRTI backbone. CONCLUSIONS: Our estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a greater 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for atazanavir compared with lopinavir regimens.

Patterns of drug resistance among newly diagnosed HIV-1 infected patients in Greece during the last decade: the crucial role of transmission networks.

INTRODUCTION: The prevalence of drug resistance is approximately 10% in Europe and North America among newly infected patients. We aim to investigate the temporal patterns of resistance among drug naive HIV-infected individuals in Greece and also to determine transmission networking among those with resistant strains. MATERIALS AND METHODS: Protease (PR) and partial reverse transcriptase (RT) sequences were determined from 2499 newly diagnosed HIV-1 patients, in Greece, during 2003-2013. Genotypic drug resistance was estimated using the HIVdb: Genotypic Resistance Interpretation Algorithm. We identified transmission clusters of resistant strains on the basis of a large collection of HIV-1 sequences from 4024 seropositives in Greece. Phylodynamic analysis was performed using a Bayesian method. RESULTS: We estimated drug resistance levels among naïve patients on the basis of all resistance mutations in PR and partial RT. The overall prevalence of resistance was 19.6% (490/2499). Resistance to NNRTIs was the most common (397/2499, 15.9%) followed by PIs (116/2499, 4.6%) and NRTIs (79/2499, 3.2%). We found a significant trend for decreasing resistance to NRTIs over time (6.7%-1.6%). There was no time trend for the overall PI and NNRTI resistance. The most frequently observed major resistant sites in PR were V82 (2.0%) and L90 (1.8%). In RT, we found E138 (58.6%), K103 (13.1%), V179 (8.4%) and T215 (7.1%), M41 (4.7%) associated with resistance to NNRTIs and NRTIs, respectively. The prevalence of K103N and E138Q were significantly increased during 2003-2013. Crucially, we found that both K103N, E138Q are associated with transmission networking within men having sex with men (MSM) and intravenous drug user (IDU) local networks. The K103N network included seropositives across Greece, while the latter only from the recent IDU outbreak in Athens metropolitan area (1). Phylodynamic analyses revealed that the exponential growth for K103N network started in 2009 (Figure 1) and for the E138Q in 2010. CONCLUSIONS: The overall resistance has been stable in Greece over time; however, specific NNRTI resistance patterns are increasing. Notably, they are associated with local transmission networking, thus suggesting that this is the cause for the increased patterns of NNRTI resistance and not multiple transmissions of resistant strains from different sources among treated individuals. Our study highlights the advance of molecular epidemiology for understanding the dynamics of resistance.

AIDS in pregnancy, part II: Treatment in the era of highly active antiretroviral therapy and management of obstetric, anesthetic, and pediatric issues.

International guidelines recommend resistance testing of maternal virus for all human immunodeficiency virus (HIV)-infected pregnant women. The use of highly active antiretroviral therapy leads to maximal virologic suppression, thus minimizing the risk of drug resistance, but it is available only in developed countries. In developing countries, the use of short-course regimens is becoming more widespread. Women infected with HIV may be at greater risk for complications during pregnancy, including ectopic pregnancy, early abortions, bacterial pneumonia, urinary tract infection, oral and recurrent vaginal thrush, malaria, and tuberculosis. Regional anesthesia is often the treatment of choice when administering anesthesia in an HIV-infected pregnant woman. Infected children present decreased survival rates, while uninfected children born to infected mothers present a higher incidence of poor weight gain, short stature, and wasting than would be expected for the general population. Transmission of HIV-1 can occur via breast-feeding.

AIDS in pregnancy, part I: epidemiology, testing, effect on disease progression, opportunistic infections, and risk of vertical transmission.

Contribution of acquired immunodeficiency syndrome/human immunodeficiency virus (HIV) infection to pregnancy mortality rates is difficult to estimate; however, it appears to be one of the leading causes of death, at least in developing countries. Prenatal HIV testing affords the best opportunity for the prevention of perinatal HIV transmission. Rapid HIV testing substantially increases the proportion of women who obtain HIV results compared with conventional enzyme-linked immunosorbent assay testing, thus maximizing perinatal HIV interventions. Pregnancy appears to have no effect on the course of HIV disease. Infections due to a variety of pathogens influence the clinical course of the HIV infection and may complicate pregnancy and increase maternal mortality. The main risk factors for mother-to-child HIV transmission are high maternal viral load and CD4 cell count <700 cells/mm3. The main protective factor is antiretroviral therapy.

Cutaneous markers of HIV infection.

Despite the development of laboratory methods, dermatological symptoms are a basic index of the presence and physical course of HIV infection. HIV infection usually undergoes a long latent period, proceeds to a period of immunodeficiency-related symptoms, and ends in an advanced immunodeficiency state characterized by opportunistic infections and neoplasms. Occasionally, dermatological manifestations can be the first signs of asymptomatic disease, indices of advanced immunodeficiency, or symptoms of opportunistic infections or neoplasms. The variety of symptoms and signs for the skin during the course of HIV infection is a consequence of the progressing immunodeficiency and therefore indicates the underlying disorder. The use of these manifestations is a challenge for clinical praxis.