Darunavir: pharmacokinetics and drug interactions.

Antiretroviral treatment (ART) for HIV is being scaled up rapidly in resource-limited countries. Treatment options are simplified and standardized, generally with one potent first-line regimen and one potent alternate first-line regimen recommended. Widespread HIV drug resistance (HIVDR) was initially feared, but reports from resource-limited countries suggest that initial ART programmes are as effective as in resource-rich countries, which should limit HIV drug resistance if programme effectiveness continues during scale-up. ART interruptions must be minimized to maintain viral suppression on the first-line regimen for as long as possible. Lack of availability of appropriate second-line drugs is a concern, as is the additional accumulation of resistance mutations in the absence of viral load testing to determine failure. The World Health Organization (WHO) recommends a minimum-resource strategy for prevention and assessment of HIVDR in resource-limited countries. The WHO's Global Network HIVResNet provides standardized tools, training, technical assistance, laboratory quality assurance, analysis of results and recommendations for guidelines and public health action. National strategies focus on assessments to guide immediate public health action to improve ART programme effectiveness in minimizing HIVDR and to guide regimen selection. Globally, WHO HIVResNet collects and analyses data to support evidence-based international policies and guidelines. Financial support is provided by major international organizations and technical support from HIVDR experts worldwide. As of December 2007, 25 countries were planning or implementing the strategy; seven countries report results in this supplement.

[1]  V. Johnson,et al.  Persistent Antiretroviral Activity of Nucleoside Analogues After Prolonged Zidovudine and Lamivudine Therapy as Demonstrated by Rapid Loss of Activity After Discontinuation , 2004, Journal of acquired immune deficiency syndromes.

[2]  J. J. Henning,et al.  Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, January 28, 2000 , 1998, HIV clinical trials.

[3]  F. Antunes,et al.  Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen , 2007, AIDS.

[4]  B. Strom,et al.  Out-of-pocket costs of HAART limit HIV treatment responses in Botswana's private sector , 2006, AIDS.

[5]  Douglas Richman,et al.  Viral Dynamics of HIV: Implications for Drug Development and Therapeutic Strategies , 1996, Annals of Internal Medicine.

[6]  Jim Y. Kim,et al.  Examining the production costs of antiretroviral drugs , 2006, AIDS.

[7]  Neil M Ferguson,et al.  Modelling the Impact of Antiretroviral Use in Resource-Poor Settings , 2006, PLoS medicine.

[8]  S. Lagakos,et al.  Response to Antiretroviral Therapy after a Single, Peripartum Dose of Nevirapine , 2007 .

[9]  Wasun Chantratita,et al.  Options for a second-line antiretroviral regimen for HIV type 1-infected patients whose initial regimen of a fixed-dose combination of stavudine, lamivudine, and nevirapine fails. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[10]  D. Bennett,et al.  World Health Organization surveys to monitor HIV drug resistance prevention and associated factors in sentinel antiretroviral treatment sites , 2008, Antiviral therapy.

[11]  B. Strom,et al.  Diagnostic accuracy of CD4 cell count increase for virologic response after initiating highly active antiretroviral therapy , 2006, AIDS.

[12]  Martin S. Hirsch,et al.  Treatment for adult HIV infection. , 2004 .

[13]  G. Rutherford,et al.  Changes in sexual behavior and risk of HIV transmission after antiretroviral therapy and prevention interventions in rural Uganda , 2006, AIDS.

[14]  M. Kamya,et al.  Free Antiretrovirals Must Not Be Restricted Only to Treatment-Naive Patients , 2005, PLoS medicine.

[15]  Fiona Ross,et al.  Working together for health , 2007, Journal of interprofessional care.

[16]  A. Davidson,et al.  Selective Drug Taking During Combination Antiretroviral Therapy in an Unselected Clinic Population , 2005, Journal of acquired immune deficiency syndromes.

[17]  K. Kamoto,et al.  Surveillance of transmitted HIV drug resistance with the World Health Organization threshold survey method in Lilongwe, Malawi , 2007, Antiviral therapy.

[18]  P. Sonnenberg,et al.  Survival from HIV-1 seroconversion in Southern Africa: a retrospective cohort study in nearly 2000 gold-miners over 10 years of follow-up , 2007, AIDS.

[19]  A. Puren,et al.  Antiretroviral drug resistance surveillance among drug-naive HIV-1-infected individuals in Gauteng Province, South Africa in 2002 and 2004 , 2008, Antiviral therapy.

[20]  D. Pillay,et al.  World Health Organization/HIVResNet Drug Resistance Laboratory Strategy , 2008, Antiviral therapy.

[21]  D. Bennett,et al.  A novel sequential sampling technique for the surveillance of transmitted HIV drug resistance by cross-sectional survey for use in low resource settings , 2008, Antiviral therapy.

[22]  S. Bautista-Arredondo,et al.  Economic impact of antiretroviral therapy prescription decisions in the context of rapid scaling-up of access to treatment: lessons from Mexico , 2006, AIDS.

[23]  S. Lawn,et al.  Conservation of First-Line Antiretroviral Treatment Regimen where Therapeutic Options are Limited , 2007, Antiviral therapy.

[24]  N. Margot,et al.  Long-term follow-up of patients taking tenofovir DF with low-level HIV-1 viremia and the K65R substitution in HIV-1 RT , 2007, AIDS.

[25]  J. Sterne,et al.  Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries , 2006, The Lancet.

[26]  S. Kinoti,et al.  The impact of HIV/AIDS on the health workforce in developing countries , 2006 .

[27]  C. Gilks,et al.  National adult antiretroviral therapy guidelines in resource-limited countries: concordance with 2003 WHO guidelines? , 2006, AIDS.

[28]  Erin N. Bodine,et al.  The antiretroviral rollout and drug-resistant HIV in Africa: insights from empirical data and theoretical models. , 2005, AIDS.

[29]  D. Bennett,et al.  Surveillance of transmitted HIV drug resistance in the Manzini-Mbabane corridor, Swaziland, in 2006 , 2008, Antiviral therapy.

[30]  L. Ivers,et al.  Efficacy of antiretroviral therapy programs in resource-poor settings: a meta-analysis of the published literature. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[31]  D. Bennett,et al.  Surveillance of transmitted HIV drug resistance among women attending antenatal clinics in Dar es Salaam, Tanzania , 2008, Antiviral therapy.

[32]  Charles Kabugo,et al.  Long-Term Experience Providing Antiretroviral Drugs in a Fee-for-Service HIV Clinic in Uganda: Evidence of Extended Virologic and CD4+ Cell Count Responses , 2005, Journal of acquired immune deficiency syndromes.

[33]  A. Harries,et al.  Acceptance of Anti-Retroviral Therapy among Patients Infected with HIV and Tuberculosis in Rural Malawi Is Low and Associated with Cost of Transport , 2006, PloS one.

[34]  M. Sweat,et al.  The impact of HIV treatment on risk behaviour in developing countries: A systematic review , 2007, AIDS care.

[35]  S. Deeks Nonnucleoside Reverse Transcriptase Inhibitor Resistance , 2001 .

[36]  Z. Grossman,et al.  Threshold survey evaluating transmitted HIV drug resistance among public antenatal clinic clients in Addis Ababa, Ethiopia , 2007, Antiviral therapy.

[37]  S. Deeks Antiretroviral treatment of HIV infected adults , 2006, BMJ : British Medical Journal.

[38]  W. Heneine,et al.  Emergence of drug-resistant HIV-1 after intrapartum administration of single-dose nevirapine is substantially underestimated. , 2005, The Journal of infectious diseases.

[39]  Richard D Moore,et al.  Response to antiretroviral therapy in HIV-infected patients attending a public, urban clinic in Kampala, Uganda. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[40]  K. Ruxrungtham,et al.  HIV drug resistance transmission threshold survey in Bangkok, Thailand , 2008, Antiviral therapy.

[41]  Soo-Yon Rhee,et al.  HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance , 2007, AIDS.

[42]  Soo-Yon Rhee,et al.  Consensus Drug Resistance Mutations for Epidemiological Surveillance: Basic Principles and Potential Controversies , 2008, Antiviral therapy.

[43]  S. Gove,et al.  The WHO public-health approach to antiretroviral treatment against HIV in resource-limited settings , 2006, The Lancet.

[44]  E. Delaporte,et al.  Antiretroviral therapy in public and private routine health care clinics in Cameroon: lessons from the Douala antiretroviral (DARVIR) initiative. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[45]  Michael S Saag,et al.  Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society--USA panel. , 2006, Topics in HIV medicine : a publication of the International AIDS Society, USA.

[46]  Mark Myatt,et al.  Recommendations for surveillance of transmitted HIV drug resistance in countries scaling up antiretroviral treatment , 2008, Antiviral therapy.

[47]  M. Holstad,et al.  Motivating HIV positive women to adhere to antiretroviral therapy and risk reduction behavior: the KHARMA Project. , 2006, Online journal of issues in nursing.

[48]  J. Stringer,et al.  Use of single-dose nevirapine for the prevention of mother-to-child transmission of HIV-1: does development of resistance matter? , 2007, American journal of obstetrics and gynecology.

[49]  P. Kaleebu,et al.  Emergence and evolution of drug resistance in the absence of viral load monitoring during 48 weeks of Combivir/Tenofovir within the DART Trial. , 2007 .

[50]  D. Bennett,et al.  Gln151 of HIV-1 reverse transcriptase acts as a steric gate towards clinically relevant acyclic phosphonate nucleotide analogues. , 2008 .

[51]  C. Golin,et al.  How Qualitative Methods Contribute to Understanding Combination Antiretroviral Therapy Adherence , 2006, Journal of acquired immune deficiency syndromes.

[52]  Raffaele Vardavas,et al.  The Emergence of HIV Transmitted Resistance in Botswana: “When Will the WHO Detection Threshold Be Exceeded?” , 2007, PloS one.

[53]  S. Deeks,et al.  Treatment of antiretroviral-drug-resistant HIV-1 infection , 2003, The Lancet.

[54]  D. Descamps,et al.  Predictors of virologic failure and resistance in HIV-infected patients treated with nevirapine- or efavirenz-based antiretroviral therapy. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[55]  P. Wright,et al.  Antiretroviral therapy in a thousand patients with AIDS in Haiti. , 2005, The New England journal of medicine.

[56]  N. Ford,et al.  Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment , 2006, The Lancet.

[57]  J. Fellay,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[58]  Sally Blower,et al.  Predicting the impact of antiretrovirals in resource-poor settings: preventing HIV infections whilst controlling drug resistance. , 2003, Current drug targets. Infectious disorders.

[59]  E. Schouten,et al.  Early warning indicators for HIV drug resistance in Malawi , 2008, Antiviral therapy.

[60]  J. Coffin,et al.  HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy , 1995, Science.

[61]  N. Ford,et al.  Sustaining access to antiretroviral therapy in the less-developed world: lessons from Brazil and Thailand , 2007, AIDS.

[62]  A. Boulle,et al.  Promoting adherence to antiretroviral therapy: the experience from a primary care setting in Khayelitsha, South Africa , 2004, AIDS.

[63]  J. Hargreaves,et al.  Adherence to TB preventive therapy for HIV-positive patients in rural South Africa: implications for antiretroviral delivery in resource-poor settings? , 2005, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[64]  P. Kaleebu,et al.  Virological response to a triple nucleoside/nucleotide analogue regimen over 48 weeks in HIV-1-infected adults in Africa , 2006, AIDS.

[65]  N. Ford,et al.  HIV Treatment in a Conflict Setting: Outcomes and Experiences from Bukavu, Democratic Republic of the Congo , 2007, PLoS medicine.

[66]  E. Wood,et al.  Balancing effectiveness and access to HIV treatment in the developing world. , 2007, AIDS.

[67]  Peter E. Hilsenrath,et al.  The World Health Report 2000 , 2002 .

[68]  Jim Y. Kim,et al.  AIDS in 2006--moving toward one world, one hope? , 2006, The New England journal of medicine.

[69]  Tara L. Kieffer,et al.  HIV-1 viral load blips are of limited clinical significance. , 2006, The Journal of antimicrobial chemotherapy.

[70]  K. D. de Cock,et al.  HIV prevention for a threatened continent: implementing positive prevention in Africa. , 2006, JAMA.

[71]  M. Egger,et al.  Substitutions due to antiretroviral toxicity or contraindication in the first 3 years of antiretroviral therapy in a large South African cohort. , 2007, Antiviral therapy.

[72]  I. Okeke,et al.  Antimicrobial resistance in developing countries , 1998, BMJ.

[73]  L. Mofenson,et al.  International recommendations on antiretroviral drugs for treatment of HIV-infected women and prevention of mother-to-child HIV transmission in resource-limited settings: 2006 update. , 2007, American journal of obstetrics and gynecology.

[74]  S. Hammer,et al.  Decay of K103N mutants in cellular DNA and plasma RNA after single-dose nevirapine to reduce mother-to-child HIV transmission , 2006, AIDS.

[75]  I. Okeke,et al.  Antimicrobial resistance in developing countries. Part II: strategies for containment. , 2005, The Lancet. Infectious diseases.

[76]  J. McIntyre REVIEW: Preventing mother‐to‐child transmission of HIV: successes and challenges , 2005, BJOG : an international journal of obstetrics and gynaecology.

[77]  O. Laeyendecker,et al.  Treatment interruptions predict resistance in HIV-positive individuals purchasing fixed-dose combination antiretroviral therapy in Kampala, Uganda , 2007, AIDS.

[78]  W. Keulen,et al.  Reduced replication of 3TC‐resistant HIV‐1 variants in primary cells due to a processivity defect of the reverse transcriptase enzyme. , 1996, The EMBO journal.

[79]  Kara Wools-Kaloustian,et al.  Viability and effectiveness of large-scale HIV treatment initiatives in sub-Saharan Africa: experience from western Kenya , 2006, AIDS.

[80]  G. Maartens,et al.  Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa , 2004, AIDS.

[81]  D. Bangsberg,et al.  Multiple Validated Measures of Adherence Indicate High Levels of Adherence to Generic HIV Antiretroviral Therapy in a Resource-Limited Setting , 2004, Journal of acquired immune deficiency syndromes.