JAIDS Journal of Acquired Immune Deficiency Syndromes (JAIDS-J ACQ IMM DEF)

Publications in this journal

• Article: http://journals.lww.com/jaids/Fulltext/2012/08153/PEPFAR_s_Evolving_HIV_Prevention_Approaches_for.14.aspx

  Needle, Richard, Fu, Joe, Beyrer, Chris, Loo, Virginia, Abdul-Quader, Abu S, McIntyre, James A, Li, Zhijun, Mbwambo, Jessie K. K, Muthui, Mercy, Pick, Billy
  JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2012;
• Article: Distribution of Cell-Free and Cell-Associated HIV Surrogates in the Colon After Simulated Receptive Anal Intercourse in Men Who Have Sex With Men

  Nicolette A. Louissaint, Sridhar Nimmagadda, Edward J. Fuchs, Rahul P. Bakshi, Ying-Jun Cao, Linda A. Lee, Jeff Goldsmith, Brian S. Caffo, Yong Du, Karen E. King, Frederick A. Menendez, Michael S. Torbenson, Craig W. Hendrix
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  ABSTRACT: Objectives: Describing the distribution and clearance of HIV surrogates within the gastrointestinal tract to inform rectal microbicide development. Design: Radiolabeled simulated HIV-infected semen was administered, imaged, and biopsied to simulate and measure colonic HIV distribution after anal intercourse. Methods: Healthy male subjects with a history of receptive anal intercourse and experience with the use of anal sex toys were recruited to this study. Apheresis isolated leukocytes were collected before simulated intercourse. These autologous leukocytes, radiolabeled with 9.25 MBq 111Indium-oxine (cell-associated HIV surrogate), and sulfur colloid particles, labeled with 37 MBq 99mTechnectium (cell-free HIV surrogate), were mixed in 3 mL autologous seminal plasma. This simulated HIV-infected semen was administered to subjects via an artificial phallus with urethra after 5 minutes of simulated intercourse. Postdosing dual isotope Single photon emission computed tomography coupled with traditional computed tomography (SPECT/CT) images were acquired at 1, 4, 8, and 24 hours. At 5 hours postdosing, colon biopsies were collected, CD4 cells were extracted, and samples analyzed for radioactivity. Results: SPECT/CT images showed similar luminal distribution for both surrogates, with migration limited to the rectosigmoid colon in all subjects. SPECT showed at least 75% overlap in distribution of both surrogates up to 4 hours after dosing. Biopsies indicate that 2.4% of CD4 cells extracted from rectosigmoid colon tissue were exogenously administered. Conclusions: Our HIV surrogates stayed within the rectosigmoid colon for 24 hours. Exogenously dosed autologous lymphocytes and HIV-sized particles migrate to similar locations and associate with the colonic tissue in the lumen.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 12/2011; 59(1):10–17.
• Article: The Interrelated Transmission of HIV-1 and Cytomegalovirus During Gestation and Delivery in the Offspring of HIV-Infected Mothers

  Woottichai Khamduang, Gonzague Jourdain, Wasna Sirirungsi, Prapaisri Layangool, Suparat Kanjanavanit, Pornsuda Krittigamas, Karin Pagdi, Rosalin Somsamai, Surat Sirinontakan, Temsiri Hinjiranandana, Wanna Ardonk, Suchat Hongsiriwon, Sirisak Nanta, Thitiporn Borkird, Marc Lallemant, Kenneth McIntosh, Nicole Ngo-Giang-Huong, For the Program for HIV Prevention and Treatment (PHPT) Study Group
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  ABSTRACT: Our objective was to analyze, in formula-fed infants, correlates of HIV mother-to-child transmission, including cytomegalovirus (CMV) infection. HIV-infected infants were matched with HIV uninfected by maternal HIV RNA in a case-control design. Infant CMV infection was determined by CMV IgG at 18 months and timed by earlier CMV IgM or CMV DNA. Correlations were assessed using logistic regression. In utero HIV infection was independently associated with congenital CMV infection (P = 0.01), intrapartum HIV infection with congenital-plus-intrapartum/neonatal CMV infection (P = 0.01), and overall HIV with overall CMV infection (P = 0.001), and prematurity (P = 0.004). Congenital and acquired CMV infections are strong independent correlates of mother-to-child HIV transmission.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 09/2011; 58(2):188-192.
• Article: HIV Infection and Progression of Carotid and Coronary Atherosclerosis: The CARE Study

  Alexandra Mangili, Joseph F Polak, Sally C Skinner, Jul Gerrior, Heidi Sheehan, Anita Harrington, Christine A Wanke
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  ABSTRACT: Background: Progression of carotid intima-media thickness (c-IMT) and coronary artery calcium (CAC) are increasingly used as surrogates for vascular risk. We assessed the predictors of c-IMT and CAC progression in a large longitudinal cohort of HIV-infected adults. Methods: c-IMT, CAC scores, and vascular and HIV risk factors were evaluated at baseline and at 3-year follow-up in 255 HIV-infected adults. Multivariate regression was used to determine the predictors of atherosclerotic progression. Results: The mean change in c-IMT per year of follow-up was 0.016 mm for the common and 0.020 mm for the internal. Significant predictors of yearly progression were age, systolic blood pressure, triglycerides, and insulin for common c-IMT and triglycerides ≥150 mg/dL, glucose >126 mg/dL, use of glucose-lowering medications, quantitative insulin sensitivity check index, high waist circumference, and current smoking for internal c-IMT. Twenty-eight percent had CAC progression. Of those with zero CAC at baseline, 32% had detectable scores at follow-up. Of those with detectable CAC at baseline, 26% had progression at follow-up. For CAC score, quantitative insulin sensitivity check index, apolipoprotein B, and triglycerides predicted progression. Those with abnormal surrogate markers at baseline were more likely to have the metabolic syndrome reversed and be started on antihypertensive medications over the 3-year follow-up period than those who had no abnormalities at baseline. Conclusions: Although c-IMT and CAC progression rates in HIV-infected patients appear higher than expected for this age and risk groups, traditional cardiovascular risk factors remain the strongest determinants of carotid and coronary atherosclerotic disease progression in HIV-infected patients. Aggressive cardiovascular risk reduction is effective at slowing the atherosclerotic progression in those with preexisting disease.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 09/2011; 58(2):148-153.
• Article: Eliminating Vertical Transmission of HIV in São Paulo, Brazil: Progress and Challenges

  Luiza Harunari Matida, Naila Janilde Seabra Santos, Alberto Novaes Jr Ramos, Maria Clara Gianna, Mariliza Henrique da Silva, Carmen Silvia Bruniera Domingues, Cristina de Albuquerque Possas, Norman Hearst, for the Study Group of Vertical Transmission of HIV and Syphilis
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  ABSTRACT: Background: HIV infection in children is an important public health problem in the world, mainly in poorer countries. If all recommendations are followed, the elimination of HIV vertical transmission is a concrete possibility. This study aims to estimate vertical transmission rates of HIV in São Paulo State, Brazil, based on pregnant women diagnosed and reported in 2006, identifying potentially associated factors. Methods: This study involves a retrospective cross-sectional analysis of information systems and records of infected pregnant women and children exposed to HIV. The rate of vertical transmission was estimated and variables associated with the antenatal, delivery, and postnatal periods were analyzed by the chi-square test, and Fisher exact test was used for variables with an expected frequency <5. The relative risks were calculated with 95% confidence intervals. Results: The rate of vertical transmission in São Paulo state was 2.7% (95% confidence interval: 1.86 to 3.94) in 2006, decreasing 83.1% in comparison with 1988-1993. The main associated variables were lack of prenatal visits or <6 visits, no antiretroviral prophylaxis during labor or neonatal use for <6 weeks, and maternal breastfeeding. Conclusions: There is a decreasing trend of HIV vertical transmission in São Paulo with levels approaching elimination, which seems to be associated with antiretroviral policy and interruption of breastfeeding. Although there are serious operational issues, conditions exist to respond effectively. São Paulo state demonstrates that it is possible to achieve advanced levels of control for this mode of HIV transmission.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2011; 57:S164-S170.
• Article: Vitamin D Deficiency in HIV-Infected and HIV-Uninfected Women in the United States

  Oluwatoyin M Adeyemi, Denis Agniel, Audrey L French, Phyllis C Tien, Kathleen Weber, Marshall J Glesby, Maria C Villacres, Anjali Sharma, Daniel Merenstein, Elizabeth T Golub, William Meyer, Mardge Cohen
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  ABSTRACT: Background: Vitamin D deficiency is of increasing concern in HIV-infected persons because of its reported association with a number of negative health outcomes that are common in HIV. We undertook this study to determine the prevalence and predictors of vitamin D deficiency among a nationally representative cohort of middle-aged, ethnically diverse, HIV-infected and HIV-uninfected women enrolled in the Women's Interagency HIV Study (WIHS). Methods: Vitamin D testing was performed by Quest Diagnostics on frozen sera using the liquid chromatography/mass spectroscopy method. Vitamin D deficiency was defined as 25(OH)D ≤20 ng/mL. Comparisons of continuous and categorical characteristics among HIV-infected and HIV-uninfected women were made by Wilcoxon tests and Pearson χ2 tests, respectively. Results: One thousand seven hundred seventy-eight women (1268 HIV positive) were studied. Sixty-three percent had vitamin D deficiency (60% HIV positive vs. 72% HIV negative; P < 0.001). Multivariable predictors of vitamin D deficiency were being African American (adjusted odds ratio 3.02), Hispanic (adjusted odds ratio 1.40), body mass index (adjusted odds ratio 1.43), age (adjusted odds ratio 0.84), HIV positive (adjusted odds ratio 0.76), glomerular filtration rate <90·mL−1·min−1 (adjusted odds ratio 0.94), and WIHS sites Los Angeles (adjusted odds ratio 0.66) and Chicago (adjusted odds ratio 0.63). In the HIV-positive women, multivariate predictors were undetectable HIV RNA (adjusted odds ratio 0.69), CD4 50-200 cells per cubic millimeter (adjusted odds ratio 1.60), CD4 <50 cells per cubic millimeter (adjusted odds ratio 1.94), and recent protease inhibitor use (adjusted odds ratio 0.67). Conclusions: In this study of more than 1700 women in the United States, most women with or without HIV infection had low vitamin D levels and African American women had the highest rates of vitamin D deficiency. An understanding of the role that vitamin D deficiency plays in non-AIDS-related morbidities is planned for investigation in WIHS.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 06/2011; 57(3):197-204.
• Article: HIV Partner Notification Is Effective and Feasible in Sub-Saharan Africa: Opportunities for HIV Treatment and Prevention

  Lillian B Brown, William C Miller, Gift Kamanga, Naomi Nyirenda, Pearson Mmodzi, Audrey Pettifor, Rosalie C Dominik, Jay S Kaufman, Clement Mapanje, Francis Martinson, Myron S Cohen, Irving F Hoffman
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  ABSTRACT: Background: Sexual partners of persons with newly diagnosed HIV infection require HIV counseling, testing and, if necessary, evaluation for therapy. However, many African countries do not have a standardized protocol for partner notification, and the effectiveness of partner notification has not been evaluated in developing countries. Methods: Individuals with newly diagnosed HIV infection presenting to sexually transmitted infection clinics in Lilongwe, Malawi, were randomized to 1 of 3 methods of partner notification: passive referral, contract referral, or provider referral. The passive referral group was responsible for notifying their partners themselves. The contract referral group was given seven days to notify their partners, after which a health care provider contacted partners who had not reported for counseling and testing. In the provider referral group, a health care provider notified partners directly. Results: Two hundred forty-five index patients named 302 sexual partners and provided locator information for 252. Among locatable partners, 107 returned for HIV counseling and testing; 20 of 82 [24%; 95% confidence interval (CI): 15% to 34%] partners returned in the passive referral arm, 45 of 88 (51%; 95% CI: 41% to 62%) in the contract referral arm, and 42 of 82 (51%; 95% CI: 40% to 62%) in the provider referral arm (P < 0.001). Among returning partners (n = 107), 67 (64%) of were HIV infected with 54 (81%) newly diagnosed. Discussion: This study provides the first evidence of the effectiveness of partner notification in sub-Saharan Africa. Active partner notification was feasible, acceptable, and effective among sexually transmitted infections clinic patients. Partner notification will increase early referral to care and facilitate risk reduction among high-risk uninfected partners.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2011; 56(5):437-442.
• Article: Atazanavir Pharmacokinetics With and Without Tenofovir During Pregnancy

  Mark Mirochnick, Brookie M Best, Alice M Stek, Edmund V Capparelli, Chengcheng Hu, Sandra K Burchett, Steven S Rossi, Elizabeth Hawkins, Michael Basar, Elizabeth Smith, Jennifer S Read, for the IMPAACT study team
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  ABSTRACT: Background: Few data are available describing atazanavir exposure during pregnancy, especially when used in combination with tenofovir, whose coadministration with atazanavir results in decreased atazanavir exposure. Design: International Maternal Pediatric Adolescent AIDS Clinical Trials 1026s is an ongoing, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included 2 cohorts receiving atazanavir/ritonavir 300 mg/100 mg once daily, either with or without tenofovir. Methods: Intensive steady-state 24-hour pharmacokinetic profiles were performed during the third trimester and at 6-12 weeks postpartum. Atazanavir was measured by reverse-phase high-performance liquid chromatography (detection limit 0.047 mcg/mL). Pharmacokinetic targets were the estimated 10th percentile atazanavir area under the concentration versus time curve [(AUC): 29.4 mcg·hr·mL−1] in nonpregnant historical controls (mean AUC = 57 mcg·hr·mL−1) and a trough concentration of 0.15 mcg/mL, the concentration target used in therapeutic drug monitoring programs. Results: Median atazanavir AUC was reduced during the third trimester compared with postpartum for subjects not receiving tenofovir (41.9 vs. 57.9 mcg·hr·mL−1, P = 0.02) and for subjects receiving tenofovir (28.8 vs. 39.6 mcg·hr·mL−1, P = 0.04). During the third trimester, AUC was below the target in 33% (6 of 18) of women not receiving tenofovir and 55% (11 of 20) of women receiving tenofovir. Trough concentration was below the target in 6% (1 of 18) of women not receiving tenofovir and 15% (3 of 20) of women receiving tenofovir. The median (range) ratio of cord blood/maternal atazanavir concentration in 29-paired samples was 0.18 (0-0.45). Conclusions: Atazanavir exposure is reduced by pregnancy and by concomitant tenofovir use. A dose increase of atazanavir/ritonavir to 400 mg/100 mg may be necessary in pregnant women to ensure atazanavir exposure equivalent to that seen in nonpregnant adults.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2011; 56(5):412-419.
• Article: Nef-trafficking intercellular highways for HIV evasion of antibody production

  Weifeng Xu, Paul A. Santini, John S. Sullivan, Bing He, Meimei Shan, Susan C. Ball, Wayne B. Dyer, Thomas J. Ketas, Amy Chadburn, Leona Cohen-Gould, Daniel M. Knowles, April Chiu, Rogier W. Sanders, Kang Chen, Andrea Cerutti
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  ABSTRACT: Contact-dependent communication between immune cells generates protection, but also facilitates viral spread. We found that macrophages formed long-range actin-propelled conduits in response to negative factor (Nef), a human immunodeficiency virus type-1 (HIV-1) protein with immunosuppressive functions. Conduits attenuated immunoglobulin G2 (IgG2) and IgA class switching in systemic and intestinal lymphoid follicles by shuttling Nef from infected macrophages to B cells through a guanine exchange factor-dependent pathway involving the amino-terminal anchor, central core and carboxy-terminal flexible loop of Nef. By showing stronger virus-specific IgG2 and IgA responses in patients harboring Nef-deficient virions, our data suggest that HIV-1 exploits intercellular highways as a “Trojan horse” to deliver Nef to B cells and evade humoral immunity systemically and at mucosal sites of entry.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2011; 56:44.
• Article: Mapping and Characterization of Vicriviroc Resistance Mutations From HIV-1 Isolated from Treatment-Experienced Subjects Enrolled in a Phase II Study (VICTOR-E1)

  Paul M McNicholas, Paul A Mann, Lisa Wojcik BSc, Ping Qiu PhD, Erin Lee, Michael McCarthy, Junwu Shen, Todd A Black, Julie M Strizki
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  ABSTRACT: Objectives: In the phase 2 VICTOR-E1 study, treatment-experienced subjects receiving 20 mg or 30 mg of the CCR5 antagonist vicriviroc (VCV), with a boosted protease containing optimized background regimen, experienced significantly greater reductions in HIV-1 viral load compared with control subjects. Among the 79 VCV-treated subjects, 15 experienced virologic failure, and of these 5 had VCV-resistant virus. This study investigated the molecular basis for the changes in susceptibility to VCV in these subjects. Methods: Sequence analysis and phenotypic susceptibility testing was performed on envelope clones from VCV-resistant virus. For select clones, an exchange of mutations in the V3 loop was performed between phenotypically resistant clones and the corresponding susceptible clones. Results: Phenotypic resistance was manifest by reductions in the maximum percent inhibition. Clonal analysis of envelopes from the 5 subjects identified multiple amino acid changes in gp160 that were exclusive to the resistant clones, however, none of the changes were conserved between subjects. Introduction of V3 loop substitutions from the resistant clones into the matched susceptible clones was not sufficient to reproduce the resistant phenotype. Likewise, changing the substitutions in the V3 loops from resistant clones to match susceptible clones only restored susceptibility in 1 clone. Conclusions: There were no clearly conserved patterns of mutations in gp160 associated with phenotypic resistance to VCV and mutations both within and outside of the V3 loop contributed to the resistance phenotype. These data suggest that genotypic tests for VCV susceptibility may require larger training sets and additional information beyond V3 sequences.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2011; 56(3):222-229.
• Article: Policy Implications of Integrating Buprenorphine/Naloxone Treatment and HIV Care

  Ruth Finkelstein, Julie Netherland, Laurie Sylla, Marc N Gourevitch, Adan Cajina, Laura Cheever, for the BHIVES Collaborative
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  ABSTRACT: Researchers, practitioners, and policymakers have long recognized the potential benefits of providing integrated substance abuse and medical care services, particularly for special populations such as people living with HIV/AIDS. Buprenorphine, an office-based pharmacological treatment for opioid dependence, offers new opportunities for integrating drug treatment into HIV care settings. However, the historical separation between the drug treatment and medical care systems has resulted in a host of policy barriers. The Buprenorphine and HIV Care Evaluation and Support initiative, a multisite demonstration project to assess the feasibility and effectiveness of integrating buprenorphine/naloxone into HIV care settings, provided an opportunity to evaluate if and how policy barriers affect efforts to integrate HIV care and addiction treatment. We found that financing issues, workforce and training issues, and the operational consequences of some conceptual differences between HIV care and addiction treatment are barriers to the full integration of buprenorphine into HIV care. We recommend changes to financing and reimbursement policies, programs to strengthen the addiction treatment skills of physicians, and cross training between the fields of addiction, medicine, drug treatment, and HIV medicine. By addressing some of the policy barriers to integration, this promising new treatment can help the thousands of people living with HIV/AIDS who are also opioid dependent.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2011; 56:S98-S104.
• Article: Scale-Up and Continuation of Antiretroviral Therapy in South African Treatment Programs, 2005–2009

  Jeffrey D Klausner, Celicia Serenata, Heidi O'Bra, Christine L Mattson, JW Brown, Melinda Wilson, Thobile Mbengashe, Thurma M Goldman
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  ABSTRACT: Background: South Africa has the greatest burden of HIV-infection in the world with about 5.2 million HIV-infected adults. In 2003, the South African Government launched a comprehensive HIV and AIDS care treatment program supported by the United States in 2004 through the President's Emergency Plan for AIDS Relief (PEPFAR). Methods: To describe the scale-up and continuation of antiretroviral therapy in South African Government and PEPFAR-supported sites in South Africa, we conducted a retrospective analysis of routinely collected program reporting data, 2005-2009. Results: From 2005 through 2009, the average rate of persons initiated on antiretroviral therapy in PEPFAR-supported South African Government treatment programs increased nearly four-fold from 6,327 a month in 2005-2006 to 24,622 a month in 2008-2009 resulting in an increase from 33,543 patients on continued treatment in April-June 2005 to 631,985 patients in July-September 2009. Of those 631,985 patients receiving treatment, 65% were women. Men were more likely to be lost to follow-up (9.2% vs. 7.8%, PR 1.18, 95% CI 1.17-1.19) and more likely to die (5.6% vs. 4.1%, PR 1.36, 95% CI 1.35-1.37) than women. Conclusions: Scale-up and continuation of antiretroviral therapy in South Africa has been a remarkable medical accomplishment. Because more women receive and continue treatment, more efforts are needed to treat and retain men.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2011; 56(3):292-295.
• Article: Pharmacodynamics of PEG-IFN-α-2a and HCV Response as a Function of IL28B Polymorphism in HIV/HCV-Coinfected Patients

  Evaldo Stanislau Affonso de Araújo, Harel Dahari, Scott J Cotler, Thomas J Layden, Avidan U Neumann, Carlos Eduardo Melo, Antonio Alci Barone
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  ABSTRACT: We examined the association between IL28B single-nucleotide polymorphism rs12979860, hepatitis C virus (HCV) kinetic, and pegylated interferon alpha-2a pharmacodynamic parameters in HIV/HCV-coinfected patients from South America. Twenty-six subjects received pegylated interferon alpha-2a + ribavirin. Serum HCV-RNA and interferon concentrations were measured frequently during the first 12 weeks of therapy and analyzed using mathematical models. African Americans and whites had a similar distribution of IL28B genotypes (P = 0.5). The IL28B CC genotype was overrepresented (P = 0.015) in patients infected with HCV genotype-3 compared with genotype-1. In both genotype-1 and genotype-3, the first-phase viral decline and the average pegylated interferon-alpha-2a effectiveness during the first week of therapy were larger (trend P ≤ 0.12) in genotype-CC compared with genotypes-TC/TT. In genotype-1 patients, the second slower phase of viral decline (days 2-29) and infected cells loss rate, δ, were larger (P = 0.02 and 0.11, respectively) in genotype-CC than in genotypes-TC/TT. These associations were not observed in genotype-3 patients.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 01/2011; 56(2):95-99.
• Article: The Clinical Impact and Cost-Effectiveness of Routine, Voluntary HIV Screening in South Africa

  Rochelle P Walensky, Robin Wood, Mariam O Fofana, Neil A Martinson, Elena Losina, Michael D April, Ingrid V Bassett, Bethany L Morris, Kenneth A Freedberg, A David Paltiel, for the Cost-Effectiveness of Preventing AIDS Complications-International Investigators
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  ABSTRACT: Background: Although 900,000 HIV-infected South Africans receive antiretroviral therapy, the majority of South Africans with HIV remain undiagnosed. Methods: We use a published simulation model of HIV case detection and treatment to examine 3 HIV screening scenarios, in addition to current practice as follows: (1) one-time; (2) every 5 years; and (3) annually. South African model input data include the following: 16.9% HIV prevalence, 1.3% annual incidence, 49% test acceptance rate, HIV testing costs of $6.49/patient, and a 47% linkage-to-care rate (including 2 sequential antiretroviral therapy regimens) for identified cases. Outcomes include life expectancy, direct medical costs, and incremental cost-effectiveness. Results: HIV screening one-time, every 5 years, and annually increase HIV-infected quality-adjusted life expectancy (mean age 33 years) from 180.6 months (current practice) to 184.9, 187.6, and 197.2 months. The incremental cost-effectiveness of one-time screening is dominated by screening every 5 years. Screening every 5 years and annually each have incremental cost-effectiveness ratios of $1570/quality-adjusted life year and $1720/quality-adjusted life year. Screening annually is very cost-effective even in settings with the lowest incidence/prevalence, with test acceptance and linkage rates both as low as 20%, or when accounting for a stigma impact at least four-fold that of the base case. Conclusions: In South Africa, annual voluntary HIV screening offers substantial clinical benefit and is very cost-effective, even with highly constrained access to care and treatment.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 12/2010; 56(1):26-35.
• Article: A CD4+ Cell Count <200 Cells per Cubic Millimeter at 2 Years After Initiation of Combination Antiretroviral Therapy Is Associated With Increased Mortality in HIV-Infected Individuals With Viral Suppression

  Mona R Loutfy, Miguel Genebat, David Moore, Janet Raboud, Keith Chan, Tony Antoniou, David Milan, Anya Shen, Marina B Klein, Curtis Cooper, [......], Sean B Rourke, Anita Rachlis, Chris Tsoukas, Julio S G Montaner, Sharon L Walmsley, Marek Smieja, Ahmed Bayoumi, Edward Mills, Robert S Hogg, and the CANOC Collaboration
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  ABSTRACT: Objective: To determine the long-term impact of immunologic discordance (viral load <50 copies/mL and CD4+ count ≤200 cells/mm3) in antiretroviral-naive patients initiating combination antiretroviral therapy (cART). Methods: Our analysis included antiretroviral-naive individuals from a population-based Canadian Observational Cohort that initiated cART after January 1, 2000, and achieved virologic suppression. Multivariable Cox proportional hazards regression was used to examine the association between 1-year and 2-year immunologic discordance and time to death from all-causes. Correlates of immunologic discordance were assessed with logistic regression. Results: Immunologic discordance was observed in 19.9% (404 of 2028) and 10.2% (176 of 1721) of individuals at 1 and 2 years after cART initiation, respectively. Two-year immunologic discordance was associated with an increased risk of death [adjusted hazard ratio = 2.69; 95% confidence interval (CI): 1.26 to 5.78]. One-year immunologic discordance was not associated with death (adjusted hazard ratio = 1.12; 95% CI: 0.54 to 2.30). Two-year immunologic discordance was associated with older age (aOR per decade = 1.23; 95% CI: 1.03 to 1.48), male gender (aOR = 1.86; 95% CI: 1.09 to 3.16), injection drug use (aOR = 2.75; 95% CI: 1.81 to 4.17), and lower baseline CD4+ count (aOR per 100 cells = 0.24; 95% CI: 0.19 to 0.31) and viral load (aOR per log10 copies/mL = 0.46; 95% CI: 0.33 to 0.65). Conclusions: Immunologic discordance after 2 years of cART in antiretroviral-naive individuals was significantly associated with an increased risk of mortality.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 11/2010; 55(4):451-459.
• Article: Raltegravir Versus Efavirenz Regimens in Treatment-Naive HIV-1-Infected Patients: 96-Week Efficacy, Durability, Subgroup, Safety, and Metabolic Analyses

  Jeffrey L Lennox, Edwin DeJesus, Daniel S Berger, Adriano Lazzarin, Richard B Pollard, Jose Valdez Ramalho Madruga, Jing Zhao, Hong Wan, Christopher L Gilbert, Hedy Teppler, Anthony J Rodgers, Richard J O Barnard, Michael D Miller, Mark J DiNubile, Bach-Yen Nguyen, Randi Leavitt, Peter Sklar, the STARTMRK Investigators
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  ABSTRACT: Background: We analyzed the 96-week results in the overall population and in prespecified subgroups from the ongoing STARTMRK study of treatment-naive HIV-infected patients. Methods: Eligible patients with HIV-1 RNA (vRNA) levels >5000 copies per milliliter and without baseline resistance to efavirenz, tenofovir, or emtricitabine were randomized in a double-blind noninferiority study to receive raltegravir or efavirenz, each combined with tenofovir/emtricitabine. Results: At week 96 counting noncompleters as failures, 81% versus 79% achieved vRNA levels <50 copies per milliliter in the raltegravir and efavirenz groups, respectively [Δ (95% confidence interval) = 2% (−4 to 9), noninferiority P < 0.001]. Mean change in baseline CD4 count was 240 and 225 cells per cubic millimeter in the raltegravir and efavirenz groups, respectively [Δ (95% confidence interval) = 15 (−13 to 42)]. Treatment effects were consistent across prespecified baseline demographic and prognostic subgroups. Fewer drug-related clinical adverse events (47% versus 78%; P < 0.001) occurred in raltegravir than efavirenz recipients. Both regimens had modest effects on serum lipids and glucose levels and on body fat composition. Conclusions: When combined with tenofovir/emtricitabine in treatment-naive patients, raltegravir exhibited durable antiretroviral activity that was noninferior to the efficacy of efavirenz through 96 weeks of therapy. Subgroup analyses were generally consistent with the overall findings. Both regimens were well tolerated.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2010; 55(1):39-48.
• Article: Three-Year Safety and Efficacy of Vicriviroc, a CCR5 Antagonist, in HIV-1-Infected Treatment-Experienced Patients

  Timothy J Wilkin, Zhaohui Su, Amy Krambrink, Jianmin Long, Wayne Greaves, Robert Gross, Michael D Hughes, Charles Flexner, Paul R Skolnik, Eoin Coakley, Catherine Godfrey, Martin Hirsch, Daniel R Kuritzkes, Roy M Gulick
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  ABSTRACT: Background: Vicriviroc, an investigational CCR5 antagonist, demonstrated short-term safety and antiretroviral activity. Methods: Phase 2, double-blind, randomized study of vicriviroc in treatment-experienced subjects with CCR5-using HIV-1. Vicriviroc (5, 10, or 15 mg) or placebo was added to a failing regimen with optimization of background antiretroviral medications at day 14. Subjects experiencing virologic failure and subjects completing 48 weeks were offered open-label vicriviroc. Results: One hundred eighteen subjects were randomized. Virologic failure (<1 log10 decline in HIV-1 RNA ≥16 weeks postrandomization) occurred by week 48 in 24 of 28 (86%), 12 of 30 (40%), 8 of 30 (27%), 10 of 30 (33%) of subjects randomized to placebo, 5, 10, and 15 mg, respectively. Overall, 113 subjects received vicriviroc at randomization or after virologic failure, and 52 (46%) achieved HIV-1 RNA <50 copies per milliliter within 24 weeks. Through 3 years, 49% of those achieving suppression did not experience confirmed viral rebound. Dual or mixed-tropic HIV-1 was detected in 33 (29%). Vicriviroc resistance (progressive decrease in maximal percentage inhibition on phenotypic testing) was detected in 6 subjects. Nine subjects discontinued vicriviroc due to adverse events. Conclusions: Vicriviroc seems safe and demonstrates sustained virologic suppression through 3 years of follow-up. Further trials of vicriviroc will establish its clinical utility for the treatment of HIV-1 infection.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2010; 54(5):470-476.