Archive for August, 2013

Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel.

JAMA. 2012 Jul 25;308(4):387-402.

Thompson MA, Aberg JA, Hoy JF, Telenti A, Benson C, Cahn P, Eron JJ, Günthard HF, Hammer SM, Reiss P, Richman DD, Rizzardini G, Thomas DL, Jacobsen DM, Volberding PA.


AIDS Research Consortium of Atlanta, 131 Ponce de Leon Ave NE, Ste 130, Atlanta, GA 30308, USA.



New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected adults in resource-rich settings.


To provide current recommendations for the treatment of adult HIV infection with ART and use of laboratory-monitoring tools. Guidelines include when to start therapy and with what drugs, monitoring for response and toxic effects, special considerations in therapy, and managing antiretroviral failure.


Data that had been published or presented in abstract form at scientific conferences in the past 2 years were systematically searched and reviewed by an International Antiviral Society-USA panel. The panel reviewed available evidence and formed recommendations by full panel consensus.


Treatment is recommended for all adults with HIV infection; the strength of the recommendation and the quality of the evidence increase with decreasing CD4 cell count and the presence of certain concurrent conditions. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir). Alternatives in each class are recommended for patients with or at risk of certain concurrent conditions. CD4 cell count and HIV-1 RNA level should be monitored, as should engagement in care, ART adherence, HIV drug resistance, and quality-of-care indicators. Reasons for regimen switching include virologic, immunologic, or clinical failure and drug toxicity or intolerance. Confirmed treatment failure should be addressed promptly and multiple factors considered.


New recommendations for HIV patient care include offering ART to all patients regardless of CD4 cell count, changes in therapeutic options, and modifications in the timing and choice of ART in the setting of opportunistic illnesses such as cryptococcal disease and tuberculosis.


August 29, 2013 at 8:43 am

The next generation of the World Health Organization’s global antiretroviral guidance.

J Int AIDS Soc. 2013 Jun 30;16:18757.

Hirnschall G, Harries AD, Easterbrook PJ, Doherty MC, Ball A.


HIV Department, World Health Organization, Geneva, Switzerland.


The 2013 World Health Organization’s (WHO) Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection provide more than 50 new recommendations across the continuum of HIV care, including recommendations on HIV testing, using antiretroviral drugs for prevention, linking individuals to HIV care and treatment services, initiating and maintaining antiretroviral therapy (ART) and monitoring treatment. Guidance is provided across all age groups and populations of adults, pregnant and breastfeeding women, adolescents and key populations. The guidelines are based on a public health approach to expanding the use of ARV drugs for HIV treatment and prevention, with a particular focus on resource-limited settings. The most important new clinical recommendations include: treating adults, adolescents and older children earlier – starting ART in all individuals with a CD4 cell count of 500 cells/mm(3) or less (but giving priority to those with advanced clinical disease or a CD4 cell count less than 350 cells/mm(3)); starting ART at any CD4 cell count in certain populations, including those with active TB (existing recommendation), Hepatitis B infection and severe chronic liver disease, HIV-positive partners in serodiscordant couples (existing recommendation), pregnant and breastfeeding women, and children younger than 5 years of age; a preferred first-line ART regimen of Tenofovir+3TC or FTC+ Efavirenz as a once-daily fixed-dose combination for adults, pregnant women, and children aged 3 years and older; and the use of viral load testing as the preferred approach to monitoring the response to ART and to diagnose treatment failure. Guidance is also provided on enhancing the efficiency and effectiveness of HIV services, including strategies to improve retention in care, and adherence to ART; task-shifting to address human resource gaps; decentralizing delivery of ART to primary health care, and integrating ART services within maternal and child health, TB or drug dependency clinics. There is additional guidance for programme managers on how to plan HIV programmes and use resources most efficiently.




ARV guidelines, WHO, adolescents, adults, children, pregnant women


August 28, 2013 at 2:41 pm

Antiretroviral therapy, pregnancy, and birth defects – A discussion on the updated data.

HIV AIDS (Auckl). 2013 Aug 1;5:181-9.

Prestes-Carneiro LE.


Immunology Department, University of Oeste Paulista, Presidente Prudente, São Paulo, Brazil ; Infectious Diseases Department, Hospital Ipiranga, São Paulo, S P, Brazil.


An increasing number of HIV-infected women of childbearing age are initiating antiretroviral therapy (ART) worldwide. This review aims to discuss updated data of the eligible ART regimens and their role in inducing birth defects in utero. Zidovudine and lamivudine plus a non-nucleoside reverse-transcriptase inhibitor or protease inhibitor (PI) is the first-line regimen applied. The role of zidovudine exposition monotherapy or associated with other ART in inducing birth defects remains inconclusive. The main organ systems involved are genitourinary and cardiovascular. For HIV-infected pregnant women, World Health Organization (WHO) guidelines up to 2010 recommend the same group of drugs that are prescribed to nonpregnant women. The exception is efavirenz, which has been associated with an increase in the risk of teratogenicity. Increased rates of birth defects were found in large cohorts and computational studies conducted recently in infants exposed to efavirenz-containing regimens. The combination of zidovudine and lamivudine and lopinavir/ritonavir is one of the most used ART regimens for prevention of mother-to-child-transmission. Conflicting data about the role of PI exposure in utero and birth defects have been reported. However, a reduced number of studies evaluating the role of PI in inducing birth defects in women are available. An association between prematurity and PI exposure in pregnancy was extensively described. Some questions arise due to the tendency of initiating ART early in the life of HIV-infected individuals or those at risk of infection. Longtime exposure to different ART regimens and the potential effect of birth-defect induction in pregnancy are not completely understood. Developing regions harbor the highest numbers of women of reproductive age exposed to ART. Most of the largest and expressive data come from developed countries, and could not be sufficiently representative of pregnant women living in developing countries.




antiretroviral therapy, birth defects, pregnancy

August 28, 2013 at 2:39 pm

Towards Universal Voluntary HIV Testing and Counselling: A Systematic Review and Meta-Analysis of Community-Based Approaches.

PLoS Med. 2013 Aug;10(8):e1001496.

Suthar AB, Ford N, Bachanas PJ, Wong VJ, Rajan JS, Saltzman AK, Ajose O, Fakoya AO, Granich RM, Negussie EK, Baggaley RC.


Department of HIV/AIDS, World Health Organization, Geneva, Switzerland.



Effective national and global HIV responses require a significant expansion of HIV testing and counselling (HTC) to expand access to prevention and care. Facility-based HTC, while essential, is unlikely to meet national and global targets on its own. This article systematically reviews the evidence for community-based HTC.


PubMed was searched on 4 March 2013, clinical trial registries were searched on 3 September 2012, and Embase and the World Health Organization Global Index Medicus were searched on 10 April 2012 for studies including community-based HTC (i.e., HTC outside of health facilities). Randomised controlled trials, and observational studies were eligible if they included a community-based testing approach and reported one or more of the following outcomes: uptake, proportion receiving their first HIV test, CD4 value at diagnosis, linkage to care, HIV positivity rate, HTC coverage, HIV incidence, or cost per person tested (outcomes are defined fully in the text). The following community-based HTC approaches were reviewed: (1) door-to-door testing (systematically offering HTC to homes in a catchment area), (2) mobile testing for the general population (offering HTC via a mobile HTC service), (3) index testing (offering HTC to household members of people with HIV and persons who may have been exposed to HIV), (4) mobile testing for men who have sex with men, (5) mobile testing for people who inject drugs, (6) mobile testing for female sex workers, (7) mobile testing for adolescents, (8) self-testing, (9) workplace HTC, (10) church-based HTC, and (11) school-based HTC. The Newcastle-Ottawa Quality Assessment Scale and the Cochrane Collaboration’s “risk of bias” tool were used to assess the risk of bias in studies with a comparator arm included in pooled estimates.  117 studies, including 864,651 participants completing HTC, met the inclusion criteria. The percentage of people offered community-based HTC who accepted HTC was as follows: index testing, 88% of 12,052 participants; self-testing, 87% of 1,839 participants; mobile testing, 87% of 79,475 participants; door-to-door testing, 80% of 555,267 participants; workplace testing, 67% of 62,406 participants; and school-based testing, 62% of 2,593 participants. Mobile HTC uptake among key populations (men who have sex with men, people who inject drugs, female sex workers, and adolescents) ranged from 9% to 100% (among 41,110 participants across studies), with heterogeneity related to how testing was offered. Community-based approaches increased HTC uptake (relative risk [RR] 10.65, 95% confidence interval [CI] 6.27-18.08), the proportion of first-time testers (RR 1.23, 95% CI 1.06-1.42), and the proportion of participants with CD4 counts above 350 cells/µl (RR 1.42, 95% CI 1.16-1.74), and obtained a lower positivity rate (RR 0.59, 95% CI 0.37-0.96), relative to facility-based approaches. 80% (95% CI 75%-85%) of 5,832 community-based HTC participants obtained a CD4 measurement following HIV diagnosis, and 73% (95% CI 61%-85%) of 527 community-based HTC participants initiated antiretroviral therapy following a CD4 measurement indicating eligibility. The data on linking participants without HIV to prevention services were limited. In low- and middle-income countries, the cost per person tested ranged from US$2-US$126. At the population level, community-based HTC increased HTC coverage (RR 7.07, 95% CI 3.52-14.22) and reduced HIV incidence (RR 0.86, 95% CI 0.73-1.02), although the incidence reduction lacked statistical significance. No studies reported any harm arising as a result of having been tested.


Community-based HTC achieved high rates of HTC uptake, reached people with high CD4 counts, and linked people to care. It also obtained a lower HIV positivity rate relative to facility-based approaches. Further research is needed to further improve acceptability of community-based HTC for key populations. HIV programmes should offer community-based HTC linked to prevention and care, in addition to facility-based HTC, to support increased access to HIV prevention, care, and treatment.


International Prospective Register of Systematic Reviews CRD42012002554 Please see later in the article for the Editors’ Summary.



August 28, 2013 at 2:36 pm

Cost-benefit analysis: HIV/AIDS prevention in migrants in Central America.

Salud Publica Mex. 2013 Jul;55 Suppl 1:S23-30.

[Article in Spanish]

Alarid-Escudero F, Sosa-Rubí SG, Fernández B, Galárraga O.


Division of Health Policy and Management, University of Minnesota, Minneapolis, Minnesota, EUA.



To quantify the costs and benefits of three HIV prevention interventions in migrants in Central America: voluntary counseling and testing, treatment of sexually transmitted infections, and condom distribution.


The methods were: a) identification and quantification of costs; b) quantification of benefits, defined as the potential savings in antiretroviral treatment of HIV cases prevented; and c) estimation of the cost-benefit ratio.


The model estimated that 9, 21 and 8 cases of HIV were prevented by voluntary counseling and testing, treatment for sexually transmitted infections and condom distribution per 10 000 migrants, respectively. In Panama, condom distribution and treatment for sexually transmitted infections had a return of US$131/USD and US$69.8/USD. Returns in El Salvador were US$2.0/USD and US$42.3/USD in voluntary counseling and testing and condom distribution, respectively.


The potential savings on prevention have a large variation between countries. Nevertheless, the cost-benefit estimates suggest that the HIV prevention programs in Central America can potentially result in monetary savings in the long run.


August 28, 2013 at 2:34 pm

Outcomes and Impact of HIV Prevention, ART and TB Programs in Swaziland – Early Evidence from Public Health Triangulation.

PLoS One. 2013 Jul 26;8(7):e69437.

van Schalkwyk C, Mndzebele S, Hlophe T, Garcia Calleja JM, Korenromp EL, Stoneburner R, Pervilhac C.


The South African Department of Science and Technology / National Research Foundation Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), University of Stellenbosch, Cape Town, South Africa.



Swaziland’s severe HIV epidemic inspired an early national response since the late 1980s, and regular reporting of program outcomes since the onset of a national antiretroviral treatment (ART) program in 2004. We assessed effectiveness outcomes and mortality trends in relation to ART, HIV testing and counseling (HTC), tuberculosis (TB) and prevention of mother to child transmission (PMTCT).


Data triangulated include intervention coverage and outcomes according to program registries (2001-2010), hospital admissions and deaths disaggregated by age and sex (2001-2010) and population mortality estimates from the 1997 and 2007 censuses and the 2007 demographic and health survey.


By 2010, ART reached 70% of the estimated number of people living with HIV/AIDS with CD4<350/mm(3), with progressively improving patient retention and survival. As of 2010, 88% of health facilities providing antenatal care offered comprehensive PMTCT services. The HTC program recorded a halving in the proportion of adults tested who were HIV-infected; similarly HIV infection rates among HIV-exposed babies halved from 2007 to 2010. Case fatality rates among hospital patients diagnosed with HIV/AIDS started to decrease from 2005-6 in adults and especially in children, contrasting with stable case fatality for other causes including TB. All-cause child in-patient case fatality rates started to decrease from 2005-6. TB case notifications as well as rates of HIV/TB co-infection among notified TB patients continued a steady increase through 2010, while coverage of HIV testing and CPT for co-infected patients increased to above 80%.


Against a background of high, but stable HIV prevalence and decreasing HIV incidence, we documented early evidence of a mortality decline associated with the expanded national HIV response since 2004. Attribution of impact to specific interventions (versus natural epidemic dynamics) will require additional data from future household surveys, and improved routine (program, surveillance, and hospital) data at district level.


August 28, 2013 at 2:33 pm

Potential benefit of dolutegravir once daily: efficacy and safety.

HIV AIDS (Auckl). 2013;5:29-40.

Fantauzzi A, Turriziani O, Mezzaroma I.


Department of Clinical Medicine, Sapienza, University of Rome, Rome, Italy.


The viral integrase enzyme has recently emerged as a primary alternative target to block HIV-1 replication, and integrase inhibitors are considered a pivotal new class of antiretroviral drugs. Dolutegravir is an investigational next-generation integrase inhibitor showing some novel and intriguing characteristics, ie, it has a favorable pharmacokinetic profile with a prolonged intracellular half-life, rendering feasible once-daily dosing without the need for ritonavir boosting and without regard to meals. Moreover, dolutegravir is primarily metabolized via uridine diphosphate glucuronosyltranferase 1A1, with a minor component of the cytochrome P450 3A4 isoform, thereby limiting drug-drug interactions. Furthermore, its metabolic profile enables coadministration with most of the other available antiretroviral agents without dose adjustment. Recent findings also demonstrate that dolutegravir has significant activity against HIV-1 isolates with resistance mutations associated with raltegravir and/or elvitegravir. The attributes of once-daily administration and the potential to treat integrase inhibitor-resistant viruses make dolutegravir an interesting and promising investigational drug. In this review, the main concerns about the efficacy and safety of dolutegravir as well as its resistance profile are explored by analysis of currently available data from preclinical and clinical studies.



HIV-1 integrase, antiretroviral drugs, dolutegravir, integrase inhibitors, once daily

August 28, 2013 at 2:30 pm

Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure.

Retrovirology. 2013 Feb 22;10:22.

Mesplède T, Quashie PK, Osman N, Han Y, Singhroy DN, Lie Y, Petropoulos CJ, Huang W, Wainberg MA.


McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.



Clinical studies have shown that integrase strand transfer inhibitors can be used to treat HIV-1 infection. Although the first-generation integrase inhibitors are susceptible to the emergence of resistance mutations that impair their efficacy in therapy, such resistance has not been identified to date in drug-naïve patients who have been treated with the second-generation inhibitor dolutegravir. During previous in vitro selection study, we identified a R263K mutation as the most common substitution to arise in the presence of dolutegravir with H51Y arising as a secondary mutation. Additional experiments reported here provide a plausible explanation for the absence of reported dolutegravir resistance among integrase inhibitor-naïve patients to date.


We now show that H51Y in combination with R263K increases resistance to dolutegravir but is accompanied by dramatic decreases in both enzymatic activity and viral replication.


Since H51Y and R263K may define a unique resistance pathway to dolutegravir, our results are consistent with the absence of resistance mutations in antiretroviral drug-naive patients treated with this drug.



August 28, 2013 at 2:29 pm

Site of Extrapulmonary Tuberculosis is Associated with HIV Infection

Clinical Infectious Diseases July 1, 2012 V.55 N.1 P.75-81

Ira L. Leeds1, Matthew J. Magee2, Ekaterina V. Kurbatova3, Carlos del Rio1,2,3, Henry M. Blumberg1,2,3, Michael K. Leonard1,3, and Colleen S. Kraft1,3,4

1Emory University School of Medicine

2Departments of Epidemiology and Global Health, Rollins School of Public Health

3Division of Infectious Diseases, Department of Medicine

4Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA

Background. In the United States, the proportion of patients with extrapulmonary tuberculosis (EPTB) has increased relative to cases of pulmonary tuberculosis. Patients with central nervous system (CNS)/meningeal and disseminated EPTB and those with human immunodeficiency virus (HIV)/AIDS have increased mortality. The purpose of our study was to determine risk factors associated with particular types of EPTB.


We retrospectively reviewed 320 cases of EPTB from 1995–2007 at a single urban US public hospital. Medical records were reviewed to determine site of EPTB and patient demographic and clinical characteristics. Multivariable logistic regression analyses were performed to determine independent associations between patient characteristics and site of disease.


Patients were predominantly male (67%), African American (82%), and US-born (76%). Mean age was 40 years (range 18–89). The most common sites of EPTB were lymphatic (28%), disseminated (23%), and CNS/meningeal (22%) disease. One hundred fifty-four (48.1%) were HIV-infected, 40% had concomitant pulmonary tuberculosis, and 14.7% died within 12 months of EPTB diagnosis. Multivariable analysis demonstrated that HIV-infected patients were less likely to have pleural (adjusted odds ratio [AOR] 0.3; 95% confidence interval [CI] .2, .6) as site of EPTB disease than HIV-uninfected patients. Among patients with EPTB and HIV-infection, patients with CD4 lymphocyte cell count <100 were more likely to have severe forms of EPTB (CNS/meningeal and/or disseminated) (AOR 1.6; 95% CI, 1.0, 2.4).


Among patients hospitalized with EPTB, patients coinfected with HIV and low CD4 counts were more likely to have CNS/meningeal and disseminated disease. Care for similar patients should include consideration of these forms of EPTB since they carry a high risk of death.


August 25, 2013 at 1:01 pm

Mortality in Hepatitis C Virus–Infected Patients With a Diagnosis of AIDS in the Era of Combination Antiretroviral Therapy

Clinical Infectious Diseases July 1, 2012 V.55 N.1 P.137-144

Andrea D. Branch1, Mark L. Van Natta2, Marie-Louise Vachon3, Douglas T. Dieterich1, Curtis L. Meinert2, and Douglas A. Jabs4,5 for the Studies of the Ocular Complications of AIDS Research Group

1Division of Liver Diseases, Mount Sinai School of Medicine, New York, New York

2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

3Division of Infectious Diseases, and Departments of


5Medicine, Mount Sinai School of Medicine, New York, New York


Before the introduction of combination antiretroviral therapy (cART), patients infected with the human immunodeficiency virus (HIV) rarely died of liver disease. In resource-rich countries, cART dramatically increased longevity. As patients survived longer, hepatitis C virus (HCV) infection became a leading cause of death; however, because patients with AIDS continue to have 5-fold greater mortality than non-AIDS patients, it is unclear whether HCV infection increases mortality in them.


In this investigation, which is part of the Longitudinal Studies of the Ocular Complications of AIDS, plasma banked at enrollment from 2025 patients with AIDS as defined by the Centers for Disease Control and Prevention were tested for HCV RNA and antibodies.


Three hundred thirty-seven patients had HCV RNA (chronic infection), 91 had HCV antibodies and no HCV RNA (cleared infection), and 1597 had no HCV markers. Median CD4+ T-cell counts/µL were 200 (chronic), 193 (cleared), and 175 (no markers). There were 558 deaths. At a median follow-up of 6.1 years, patients with chronic HCV had a 50% increased risk of mortality compared with patients with no HCV markers (relative risk [RR], 1.5; 95% confidence interval [CI], 1.2–1.9; P = .001) in an adjusted model that included known risk factors. Mortality was not increased in patients with cleared infection (RR, 0.9; 95% CI, .6–1.5; P = .82). In patients with chronic HCV, 20.4% of deaths were liver related compared with 3.8% in patients without HCV.


Chronic HCV infection is independently associated with a 50% increase in mortality among patients with a diagnosis of AIDS, despite competing risks. Effective HCV treatment may benefit HIV/HCV-coinfected patients with AIDS.


August 25, 2013 at 12:58 pm

Older Posts


August 2013

Posts by Month

Posts by Category