| 1. Title: Evaluation of transmitted HIV drug resistance among recently-infected antenatal clinic attendees in four Central African countries. Author: Aghokeng AF; Vergne L; Mpoudi-Ngole E; Mbangue M; Deoudje N; Mokondji E; Nambei WS; Peyou-Ndi MM; Moka JJ; Delaporte E; Peeters M Source: Antiviral therapy. 2009;14(3):401-11. Abstract: BACKGROUND: The rapid expansion of antiretroviral treatment in resource-limited settings is raising concerns regarding the emergence and transmission of HIV drug resistance (HIVDR). We evaluated the extent of transmission of drug-resistant HIV strains in four Central African countries: the Republic of Congo, Central African Republic, Chad and Cameroon. METHODS: The World Health Organization (WHO) HIVDR threshold survey was implemented in major treatment areas in each country. Pregnant women who were aged <25 years, who were at first pregnancy and who were HIV type-1-positive were enrolled at each site in 2006-2007 for genotyping. HIVDR prevalence was categorized using the WHO threshold survey binomial sequential sampling method. RESULTS: The prevalence of HIVDR in Brazzaville and Bangui sites could not be classified because the eligible sample number was not reached. HIVDR prevalence was low (<5%) in N'Djamena for all drug classes. In Yaounde, we found one individual with the D67D/N mutation and two with K103N. HIVDR prevalence was categorized as low (<5%) for protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs), and moderate (> or =5-< or =15%) for non-NRTIs (NNRTIs). HIVDR prevalence in Douala was low for PIs and NNRTIs, and moderate for NRTIs as we identified one individual with M184V plus K101E plus G190A mutations and a second with D67D/N. CONCLUSIONS: The moderate HIVDR prevalence found in Yaounde and Douala indicate that efforts should be made in Cameroon to prevent HIVDR; however, additional surveys are needed to confirm this trend. This study highlighted challenges presented by the WHO methodology, such as additional costs, workload, difficulties in acquiring even small sample numbers and the necessity for better quality assurance of HIV testing and record keeping at antenatal clinics. Language: English Keywords: CAMEROON | CENTRAL AFRICAN REPUBLIC | CHAD | REPUBLIC OF THE CONGO | RESEARCH REPORT | SAMPLING STUDIES | PREGNANT WOMEN | PERSONS LIVING WITH HIV/AIDS | HIV TRANSMISSION | ANTIRETROVIRAL DRUGS | DRUG RESISTANCE | PREVALENCE | ANTENATAL CARE | Developing Countries | Africa, Western | Africa, Sub Saharan | Africa | Africa, Central | Studies | Research Methodology | Population Characteristics | Demographic Factors | Population | HIV Infections | Viral Diseases | Diseases | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Measurement | Maternal Health Services | Maternal-Child Health Services | Primary Health Care Document Number: 342346 |
2.  Peer Reviewed Title: Pregnancy and optimal care of HIV-infected patients. Author: Anderson BL; Cu-Uvin S Source: Clinical Infectious Diseases. 2009 Feb 15;48(4):449-55. Abstract: Human immunodeficiency virus (HIV) infection during pregnancy is a condition that requires multidisciplinary care. Care must be rendered that is appropriate for both the mother and the fetus. Prevention of mother-to-child transmission of HIV is of paramount concern. To prevent transmission, universal testing for HIV infection in pregnant women is ideal. In the United States and other developed countries, great strides have been made toward decreasing the risk of HIV transmission to infants to <2% with use of a combination of highly active antiretroviral therapy during the antepartum period and during labor and delivery, scheduled cesarean section when appropriate, avoidance of breast-feeding, and 6 weeks of zidovudine prophylaxis for infants. The continuation of antiretroviral therapy after delivery depends on the needs of the mother with regard to treatment of her own health. In resource-limited countries, where simplified and shortened courses of antiretroviral regimens have been used, reduction in mother-to-child transmission has also been shown, although not as effectively as that with highly active antiretroviral therapy. In these settings, exclusive breast-feeding for 6 months is recommended to reduce the risk of postnatal transmission. Language: English Keywords: UNITED STATES OF AMERICA | DEVELOPING COUNTRIES | RECOMMENDATIONS | PREGNANT WOMEN | PREVENTION OF MOTHER-TO-CHILD TRANSMISSION | HIV TESTING | ANTIRETROVIRAL DRUGS | ADMINISTRATION AND DOSAGE | DRUG RESISTANCE | ANTIRETROVIRAL THERAPY | RISK FACTORS | CESAREAN SECTION | BREASTFEEDING | Developed Countries | North America | Americas | Population Characteristics | Demographic Factors | Population | Disease Transmission Control | Prevention and Control | Diseases | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Treatment | Drugs | HIV | HIV Infections | Viral Diseases | Obstetrical Surgery | Surgery | Infant Nutrition | Nutrition Document Number: 342644 |
| 3. Title: RISUG: a potential candidate for the entry inhibitor group of antiretroviral drugs. Author: Banerjee S; Guha SK Source: Medical Hypotheses. 2009 Aug;73(2):150-2. Abstract: Entry inhibitors are a group of antiretroviral drug which prevents HIV from entering human immune cells. They include both fusion and attachment inhibitors. A hypothesis is put forward in which a new male contraceptive drug with proven antimicrobial property is proposed as a possible candidate for the entry inhibitor group of antiretroviral drugs. The proposed mechanism of action involves (i) interaction with gp120 and thereby preventing binding to CD4 and (ii) competitive binding with the viral glycoprotein and inhibit the glycoprotein - cell surface glyocosaminoglycan Heparan Sulfate (HS) interaction. A new drug RISUG (Reversible Inhibition of Sperm Under Guidance) presently undergoing Phase III clinical trials throughout India for its contraceptive effect in male has also antimicrobial actions. RISUG is a chemical complex of styrene maleic anhydride (SMA(AN)) and dimethyl sulfoxide. On injection into the vas deferens, it reacts with the components of intravas fluid, the spermatic fluid and gets converted to styrene maleic acid (SMA(AC)) and breakdown products like mandelic acid. An anti HIV activity of RISUG is likely due to its electrical charge and mandelic acid generation. For experimental validation HIV in vitro assays can be performed which will involve infectivity assays, luciferase assay and soluble gp120 assays. A positive result from the studies will validate the hypothesis. Language: English Keywords: INDIA | RESEARCH PROPOSAL | DRUGS | CONTRACEPTIVE AGENTS, MALE | MICROBICIDES | ANTIRETROVIRAL DRUGS | HIV INFECTIONS | IMMUNE SYSTEM | ANTIGEN-ANTIBODY REACTIONS | Asia, Southern | Asia | Developing Countries | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Contraceptive Agents | Contraception | Family Planning | Viral Diseases | Diseases | Physiology | Biology | Antibodies | Immunologic Factors | Immunity Document Number: 342410 |
| 4. Title: Antiretroviral drug resistance surveillance among treatment-naive human immunodeficiency virus type 1-infected individuals in Angola: evidence for low level of transmitted drug resistance. Author: Bartolo I; Rocha C; Bartolomeu J; Gama A; Fonseca M; Mendes A; Cristina F; Thamm S; Epalanga M; Silva PC; Taveira N Source: Antimicrobial Agents and Chemotherapy. 2009 Jul;53(7):3156-8. Abstract: The prevalence of transmitted human immunodeficiency virus type 1 drug resistance in Angola in 2001 in 196 untreated patients was investigated. All subtypes were detected, along with unclassifiable and complex recombinant strains. Numerous new polymorphisms were identified in the reverse transcriptase and protease. Two (1.6%) unrelated patients harbored nucleoside reverse transcriptase inhibitor- and nonnucleoside reverse transcriptase inhibitor-resistant viruses (mutations: M41L, D67N, M184V, L210W, T215Y or T215F, and K103N). Continued surveillance of drug resistance is required for maximization of ART efficacy in Angola. Language: English Keywords: ANGOLA | RESEARCH REPORT | PREVALENCE | PERSONS LIVING WITH HIV/AIDS | CLIENTS | DRUG RESISTANCE | ANTIRETROVIRAL DRUGS | HIV | LABORATORY PROCEDURES | Developing Countries | Africa, Southern | Africa, Sub Saharan | Africa | Measurement | Research Methodology | HIV Infections | Viral Diseases | Diseases | Program Activities | Programs | Organization and Administration | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Laboratory Examinations and Diagnoses | Examinations and Diagnoses Document Number: 342987 |
| 5. Peer Reviewed Title: HIV-1 genetic diversity and transmitted drug resistance in health care settings in Maputo, Mozambique. Author: Bartolo I; Casanovas J; Bastos R; Rocha C; Abecasis AB; Folgosa E; Mondlane J; Manuel R; Taveira N Source: Journal of Acquired Immune Deficiency Syndromes. 2009 Jul 1;51(3):323-31. Abstract: OBJECTIVES: To characterize HIV-1 diversity and transmitted drug resistance in persons with access to care and treatment in Maputo, Mozambique. METHODS: Samples were collected in 2002-2004 from 144 drug-naive patients attending public hospitals and private clinics. Plasma viremia, CD4, and CD8 cell counts were determined for each patient. The Stanford Algorithm was used for resistance genotyping on pol sequences. Subtyping was done by phylogenetic analysis. RESULTS: Most patients had high viral load (mean, 5.0 log copies/mL) and low CD4 cell counts (median, 260 CD4 cells/microL). Protease and/or reverse transcriptase sequences were obtained from 104 (72%) samples. Patients harbored subtypes C (80.8%), G (3.8%), CRF37_cpx (6.7%), untypable (U) (1.0%), and recombinant strains (7.7%) comprising the A, C, D, F, and U clades. There were no major protease inhibitor resistance mutations. Mutations conferring resistance to the nucleoside/nucleotide reverse transcriptase inhibitors and/or nonnucleoside reverse transcriptase inhibitors were found in 4 (4/68; 5.9%) patients. Phylogenetic analysis suggested an imported origin for 2 resistant variants. CONCLUSIONS: The HIV-1 epidemic in Maputo is evolving rapidly in genetic complexity due to the recent introduction of all major subtypes and recombinant forms. Continued surveillance of drug resistance in treated and untreated populations is needed to prevent further transmission of HIV drug-resistant variants and maximize the efficacy of antiretroviral therapy in Maputo. Language: English Keywords: MOZAMBIQUE | RESEARCH REPORT | SAMPLING STUDIES | CLIENTS | PERSONS LIVING WITH HIV/AIDS | HIV INFECTIONS | GENETICS | ANTIRETROVIRAL THERAPY | ANTIRETROVIRAL DRUGS | DRUG RESISTANCE | MONITORING | Africa, Southern | Africa, Sub Saharan | Africa | Developing Countries | Studies | Research Methodology | Program Activities | Programs | Organization and Administration | Viral Diseases | Diseases | Biology | HIV | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Evaluation Document Number: 342148 |
| 6. Title: Primary and secondary tuberculosis preventive treatment in HIV clinics: simulating alternative strategies. Author: Basu S; Maru D; Poolman E; Galvani A Source: International Journal of Tuberculosis and Lung Disease. 2009 May;13(5):652-8. Abstract: BACKGROUND: Isoniazid preventive treatment (IPT) has been recommended for human immunodeficiency virus (HIV) infected individuals. OBJECTIVE/DESIGN: We used a mathematical model to simulate the benefits and risks of preventive treatment delivered through antiretroviral (ARV) clinics using clinical data from Botswana. RESULTS: Preventive treatment was found to reduce the incidence of tuberculosis (TB) by at least 12 cases per 100000 population per year versus the scenario without such treatment over a 50-year simulation. Isoniazid (INH) resistant TB was observed to increase by <1% per year, even when using pessimistic assumptions about resistance emergence. The use of tuberculin skin testing had little impact as a screening procedure, while secondary treatment was observed to nearly double the impact of a preventive treatment program. Regardless of whether or not preventive treatment was implemented, INH-resistant TB rose in the context of increasing HIV prevalence, but was minimally amplified by preventive treatment itself. CONCLUSIONS: IPT programs implemented through ARV clinics may be effective at reducing TB incidence. The resistance contribution of IPT appears unlikely to supersede its overall incidence and mortality benefits. Language: English Keywords: BOTSWANA | RESEARCH REPORT | MATHEMATICAL MODEL | PERSONS LIVING WITH HIV/AIDS | CLIENTS | TUBERCULOSIS | DRUGS | TESTING | ANTIRETROVIRAL DRUGS | DRUG RESISTANCE | INCIDENCE | Africa, Southern | Africa, Sub Saharan | Africa | Developing Countries | Theoretical Models | Research Methodology | HIV Infections | Viral Diseases | Diseases | Program Activities | Programs | Organization and Administration | Infections | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Measurement Document Number: 341945 |
| 7. Peer Reviewed Title: Peripheral neuropathy in HIV-positive patients at an antiretroviral clinic in Lilongwe, Malawi. Author: Beadles WI; Jahn A; Weigel R; Clutterbuck D Source: Tropical Doctor. 2009 Apr;39(2):78-80. Abstract: Peripheral neuropathy (PN) is common in the setting of antiretroviral (ARV) programmes in resource-limited settings and poses significant challenges in assessment and management. A retrospective analysis was undertaken of prevalence and management of PN in a cohort of 3341 patients on highly active antiretroviral therapy. A first line ARV regimen containing stavudine (D4T) is used for clinically eligible patients. Amitriptyline is prescribed for symptom relief and in cases of persistent or escalating symptoms zidovudine (AZT) is substituted for D4T. Leg pain or numbness was reported in 1173 patients (35%). However, only 428 (13%) were given a diagnosis of PN, 228 (7%) were prescribed amitriptyline and 200 (6%) were switched to AZT. A recent pharmokinetic study in this population showed a high Cmax of D4T with the generic combination triomune (D4T 40 mg). This could account for the high prevalence of PN. The optimum time for switch to a non-D4T containing regimen is unknown. Language: English Keywords: MALAWI | RESEARCH REPORT | RETROSPECTIVE STUDIES | CLIENTS | ANTIRETROVIRAL THERAPY | ANTIRETROVIRAL DRUGS | SIDE EFFECTS | NEUROLOGIC EFFECTS | PREVALENCE | SIGNS AND SYMPTOMS | TOXICITY | Africa, Southern | Africa, Sub Saharan | Africa | Developing Countries | Studies | Research Methodology | Program Activities | Programs | Organization and Administration | HIV | HIV Infections | Viral Diseases | Diseases | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Physiology | Biology | Measurement Document Number: 341785 |
| 8. Peer Reviewed Title: Expanding antiretroviral options in resource-limited settings--a cost-effectiveness analysis. Author: Bendavid E; Wood R; Katzenstein DA; Bayoumi AM; Owens DK Source: Journal of Acquired Immune Deficiency Syndromes. 2009 Sep 1;52(1):106-13. Abstract: BACKGROUND: Current World Health Organization (WHO) guidelines for treatment of HIV in resource-limited settings call for 2 antiretroviral regimens. The effectiveness and cost-effectiveness of increasing the number of antiretroviral regimens is unknown. METHODS: Using a simulation model, we compared the survival and costs of current WHO regimens with two 3-regimen strategies: an initial regimen of 3 nucleoside reverse transcriptase inhibitors followed by the WHO regimens and the WHO regimens followed by a regimen with a second-generation boosted protease inhibitor (2bPI). We evaluated monitoring with CD4 counts only and with both CD4 counts and viral load. We used cost and effectiveness data from Cape Town and tested all assumptions in sensitivity analyses. RESULTS: Over the lifetime of the cohort, 25.6% of individuals failed both WHO regimens by virologic criteria. However, when patients were monitored using CD4 counts alone, only 6.5% were prescribed additional highly active antiretroviral therapy due to missed and delayed detection of failure. The life expectancy gain for individuals who took a 2bPI was 6.7-8.9 months, depending on the monitoring strategy. When CD4 alone was available, adding a regimen with a 2bPI was associated with an incremental cost-effectiveness ratio of $2581 per year of life gained, and when viral load was available, the ratio was $6519 per year of life gained. Strategies with triple-nucleoside reverse transcriptase inhibitor regimens in initial therapy were dominated. Results were sensitive to the price of 2bPIs. CONCLUSIONS: About 1 in 4 individuals who start highly active antiretroviral therapy in sub-Saharan Africa will fail currently recommended regimens. At current prices, adding a regimen with a 2bPI is cost effective for South Africa and other middle-income countries by WHO standards. Language: English Keywords: SOUTH AFRICA | RESEARCH REPORT | THEORETICAL MODELS | PERSONS LIVING WITH HIV/AIDS | ANTIRETROVIRAL THERAPY | ANTIRETROVIRAL DRUGS | ADMINISTRATION AND DOSAGE | COST EFFECTIVENESS | MONITORING | WHO | IMMUNOLOGICAL EFFECTS | LIFE EXPECTANCY | Developing Countries | Africa, Southern | Africa, Sub Saharan | Africa | Research Methodology | HIV Infections | Viral Diseases | Diseases | HIV | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Drugs | Evaluation Indexes | Quantitative Evaluation | Evaluation | UN | International Agencies | Organizations | Political Factors | Sociocultural Factors | Immunity | Immune System | Physiology | Biology | Length of Life | Mortality | Population Dynamics | Demographic Factors | Population Document Number: 342908 |
| 9. Peer Reviewed Title: Judicialisation of the right to health in Brazil. Author: Biehl J; Petryna A; Gertner A; Amon JJ; Picon PD Source: Lancet. 2009 Jun 27;373(9682):2182-4. Abstract: This article examines Brazil's constitutional right to health and their pharmaceutical access. It states that Brazil must raise their funding for essential medicines and pursue strategies to ensure universal availability of medicines that the government has a legal responsibility to provide in order to reduce vulnerability to disease. Language: English Keywords: BRAZIL | SUMMARY REPORT | HUMAN RIGHTS | PUBLIC HEALTH | HEALTH POLICY | ANTIRETROVIRAL DRUGS | PHARMACY DISTRIBUTION | PROGRAM EFFICIENCY | FEES | South America, Eastern | South America | Latin America | Americas | Developing Countries | Political Factors | Sociocultural Factors | Health | Policy | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Nonclinical Distribution | Distributional Activities | Program Activities | Programs | Organization and Administration | Program Evaluation | Financial Activities | Economic Factors Document Number: 342054 |
| 10. Title: [Assessment of adherence to antiretroviral drugs in a municipality in southern Brazil] Avaliacao da adesao aos anti-retrovirais em um municipio no Sul do Brasil. Author: Blatt CR; Citadin CB; Souza FG; Mello RS; Galato D Source: Revista Da Sociedade Brasileira De Medicina Tropical. 2009 Mar-Apr;42(2):131-6. Abstract: The aim of this research is to assess predicting factors and adherence levels to antiretrovirals through self-report and the date of drug retrieval. It is a transversal study in which 67 patients were interviewed. Patients who used more than 90% of doses were considered to have complied with the treatment. Results of adherence were: self-reports (72.7%); calculated using dosage forgotten on the last day (70%); in three (76.1%) days; in seven (80.5%) days; and in fifteen (80.5%) days; calculated using the date of drug retrieval in a period of three (53.7%) months; and in six (47.8%) months. Variables significantly associated with adherence were: educational level, living with the family, refer good adherence, positive assessment of the antiretroviral therapy, a diagnosis of an opportunistic disease, NADIR greater than 200 cells/mm(3) and being in first-time treatment. To improve adherence rates individual and collective strategies should be elaborated taking into account factors which have been identified as negatively effecting adherence. Language: Portuguese Keywords: BRAZIL | RESEARCH REPORT | INTERVIEWS | CLIENTS | PERSONS LIVING WITH HIV/AIDS | ANTIRETROVIRAL DRUGS | ANTIRETROVIRAL THERAPY | USER COMPLIANCE | TREATMENT | ADMINISTRATION AND DOSAGE | PROGRAM EFFECTIVENESS | South America, Eastern | South America | Latin America | Americas | Developing Countries | Data Collection | Research Methodology | Program Activities | Programs | Organization and Administration | HIV Infections | Viral Diseases | Diseases | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | HIV | Behavior | Drugs | Program Evaluation Document Number: 342167 |
| 11. Peer Reviewed Title: Financial barriers to HIV treatment in Yaounde, Cameroon: first results of a national cross-sectional survey. Author: Boyer S; Marcellin F; Ongolo-Zogo P; Abega SC; Nantchouang R; Spire B; Moatti JP Source: Bulletin of the World Health Organization. 2009 Apr;87(4):279-87. Abstract: OBJECTIVE: To assess the extent to which user fees for antiretroviral therapy (ART) represent a financial barrier to access to ART among HIV-positive patients in Yaounde, Cameroon. METHODS: Sociodemographic, economic and clinical data were collected from a random sample of 707 HIV-positive patients followed up in six public hospitals of the capital city (Yaounde) and its surroundings through face-to-face interviews carried out by trained interviewers independently from medical staff and medical questionnaires filled out by prescribing physicians. Logistic regression models were used to identify factors associated with self-reported financial difficulties in purchasing ART during the previous 3 months. FINDINGS: Of the 532 patients treated with ART at the time of the survey, 20% reported financial difficulty in purchasing their antiretroviral drugs during the previous 3 months. After adjustment for socioeconomic and clinical factors, reports of financial difficulties were significantly associated with lower adherence to ART (odds ratio, OR: 0.24; 95% confidence interval, CI: 0.15-0.40; P < 0.0001) and with lower CD4+ lymphocyte (CD4) counts after 6 months of treatment (OR: 2.14; 95% CI: 1.15-3.96 for CD4 counts < 200 cells/microl; P = 0.04). CONCLUSION: Removing a financial barrier to treatment with ART by eliminating user fees at the point of care delivery, as recommended by WHO, could lead to increased adherence to ART and to improved clinical results. New health financing mechanisms based on the public resources of national governments and international donors are needed to attain universal access to drugs and treatment for HIV infection. Language: English Keywords: CAMEROON | RESEARCH REPORT | CROSS SECTIONAL ANALYSIS | CLIENTS | PERSONS LIVING WITH HIV/AIDS | FEES | ANTIRETROVIRAL THERAPY | OBSTACLES | TREATMENT | ANTIRETROVIRAL DRUGS | PROGRAM ACCESSIBILITY | Developing Countries | Africa, Western | Africa, Sub Saharan | Africa | Research Methodology | Program Activities | Programs | Organization and Administration | HIV Infections | Viral Diseases | Diseases | Financial Activities | Economic Factors | HIV | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Program Evaluation Document Number: 342978 |
| 12. Peer Reviewed Title: Response to zidovudine/didanosine-containing combination antiretroviral therapy among HIV-1 subtype C-infected adults in Botswana: two-year outcomes from a randomized clinical trial. Author: Bussmann H; Wester CW; Thomas A; Novitsky V; Okezie R; Muzenda T; Gaolathe T; Ndwapi N; Mawoko N; Widenfelt E; Moyo S; Musonda R; Mine M; Makhema J; Moffat H; Essex M; Degruttola V; Marlink RG Source: Journal of Acquired Immune Deficiency Syndromes. 2009 May 1;51(1):37-46. Abstract: BACKGROUND: Numerous national antiretroviral (ARV) treatment initiatives offering protease inhibitor-sparing combination antiretroviral therapy (cART) have recently commenced in southern Africa, the first of which began in Botswana in January 2002. Evaluation of the efficacy and tolerability of various protease inhibitor-sparing cART regimens requires intensive study in the region, as does investigation of the development of drug resistance and the optimal means of sustaining adherence. The "Tshepo" Study is the first large-scale, randomized, clinical trial that addresses these important issues among HIV-1 subtype C-infected ARV treatment-naive adults in southern Africa. METHODS: The Tshepo Study is a completed, open-labeled, randomized study that enrolled 650 ARV-naive adults between December 2002 and 2004. The study is a 3 x 2 x 2 factorial design comparing the efficacy and tolerability among factors: (1) 3 combinations of nucleoside reverse transcriptase inhibitors (NRTIs): zidovudine (ZDV) + lamivudine (3TC), ZDV + didanosine (ddI), and stavudine (d4T) + 3TC; (2) 2 different nonnucleoside reverse transcriptase inhibitors (NNRTIs): nevirapine and efavirenz; and (3) 2 different adherence strategies: the current national "standard of care" versus an "intensified adherence strategy" incorporating a "community-based directly observed therapy." Study patients were stratified into 2 balanced CD4 T-cell count groups: less than 201 versus 201-350 cells per cubic millimeter with viral load greater than 55,000 copies per milliliter. Following Data Safety Monitoring Board recommendations in April 2006, ZDV/ddI-containing arms were discontinued due to inferiority in primary end point, namely, virologic failure with resistance. We report both overall data and pooled data from patients receiving ZDV/ddI- versus ZDV/3TC- and d4T/3TC-containing cART through April 1, 2006. RESULTS: Four hundred fifty-one females (69.4%) and 199 males with a median age of 33.3 years were enrolled into the study. The median follow-up as of April 1, 2006, was 104 weeks, and loss to follow-up rate at 2 years was 4.1%. The median baseline CD4 T-cell count was 199 cells per cubic millimeter [interquartile ratio (IQR) 136-252], and the median plasma HIV-1 RNA level was 193,500 copies per milliliter (IQR 69-250, 472-500). The proportion of participants with virologic failure and genotypic resistance mutations was 11% in those receiving ZDV/ddI-based cART versus 2% in those receiving either ZDV/3TC- or d4T/3TC-based cART (P = 0.002). The median CD4 T-cell count increase at 1 year was 137 cells per cubic millimeter (IQR 74-223) and 199 cells per cubic millimeter (IQR 112-322) at 2 years with significantly lower gain in the ZDV/ddI arm. At 1 and 2 years, respectively, 92.0% and 88.8% of patients had an undetectable plasma HIV-1 RNA level (< or = 400 copies/mL). Kaplan-Meier survival estimates at 1 and 2 years were 96.6% and 95.4%. One hundred twenty patients (18.2%) had treatment-modifying toxicities, of which the most common were lipodystrophy, anemia, neutropenia, and Stevens-Johnson syndrome. There was a trend toward difference in time to treatment-modifying toxicity by pooled dual-NRTI combination and no difference in death rates. CONCLUSIONS: The preliminary study results show overall excellent efficacy and tolerability of NNRTI-based cART among HIV-1 subtype C-infected adults. ZDV/ddI-containing cART, however, is inferior to the dual NRTIs d4T/3TC or ZDV/3TC when used with an NNRTI for first-line cART. Language: English Keywords: BOTSWANA | RESEARCH REPORT | CLINICAL TRIALS | COMPARATIVE STUDIES | PERSONS LIVING WITH HIV/AIDS | ADULTS | ANTIRETROVIRAL THERAPY | ANTIRETROVIRAL DRUGS | ADMINISTRATION AND DOSAGE | USER COMPLIANCE | DRUG RESISTANCE | IMMUNOLOGICAL EFFECTS | SIDE EFFECTS | Africa, Southern | Africa, Sub Saharan | Africa | Developing Countries | Clinical Research | Research Methodology | Studies | HIV Infections | Viral Diseases | Diseases | Age Factors | Population Characteristics | Demographic Factors | Population | HIV | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Drugs | Behavior | Immunity | Immune System | Physiology | Biology Document Number: 342371 |
| 13. Peer Reviewed Title: A visual dosing aid for first-line pediatric antiretroviral treatment in resource-poor settings. Author: Callens SF; Westreich D; Kitetele F; Lusiama J; Shabani N; Belhorn T; Colebunders R; Behets F; Van Rie A Source: Journal of Tropical Pediatrics. 2009 Apr;55(2):135-7. Abstract: The visual dosing aid (VDA) was developed to facilitate dosing calculations in response to children's; growth and weight during antiretroviral treatment. The theoretical accuracy of the VDA was assessed using anthropometric data from 55 children receiving care in the USA and 324 children in the Democratic Republic of the Congo. The VDA dose was similar to the WHO recommended dose. A potentially significant relative dosing difference of >or=20% occurred in <3% of children for NVP, AZT and d4T, but was observed in 20% for 3TC, overdosing being more frequent. The VDA compared well with generic pediatric fixed dose combination tablets. Results did not differ between sites. The VDA enables accurate dosing of pediatric ART in distinct populations and could facilitate roll-out of pediatric ART in resource-poor settings. Language: English Keywords: DEMOCRATIC REPUBLIC OF THE CONGO | RESEARCH REPORT | CHILDREN | ANTIRETROVIRAL DRUGS | ANTIRETROVIRAL THERAPY | TREATMENT | ADMINISTRATION AND DOSAGE | BODY WEIGHT | Developing Countries | Africa, Central | Africa, Sub Saharan | Africa | Youth | Age Factors | Population Characteristics | Demographic Factors | Population | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | HIV | HIV Infections | Viral Diseases | Diseases | Drugs | Physiology | Biology Document Number: 331199 |
| 14. Title: Three-year outcome data of second-line antiretroviral therapy in Ugandan adults: good virological response but high rate of toxicity. Author: Castelnuovo B; John L; Lutwama F; Ronald A; Spacek LA Source: Journal of the International Association of Physicians in AIDS Care. 2009 Jan-Feb;8(1):52-59. Abstract: Objective: To evaluate the safety and virological response to lopinavir/ritonavir containing second-line therapy after failing a first line nonnucleoside reverse transcriptase inhibitor NNRTI) based regimen. Design. Prospective 36 months cohort study of patients switched to zidovudine/stavudine plusdidanosine plus lopinavir/ritonavir capsules as second-line regimen. Methodology. Structured interview, medical examination and laboratory assessment performed every 6 months. Results. We enrolled 40 patients; 1 died and 3 were lost to follow-up. Median CD4+count at baseline was 108cell/microL, median log viral load was 4.8 copies/mL. Sixteen (40%) patients had baseline genotypic resistant test, 14 (87%) had lamivudine resistance mutations, and all had NNRTIs resistance mutations. At month 36, 82% of the patients achieved viral suppression (<400copies/mL) and the median increase in CD4+count was 214 cell/microL, (interquartile range: 128-295). Twenty-five patients (62%) experienced at least one adverse event. Conclusions. Our study confirms lopinavir/ritonavir-based second-line regimen but with a high rate of toxicities. Language: English Keywords: AFRICA | UGANDA | RESEARCH REPORT | ADULTS | CLIENTS | PERSONS LIVING WITH HIV/AIDS | ANTIRETROVIRAL DRUGS | ANTIRETROVIRAL THERAPY | TOXICITY | Developing Countries | Africa, Eastern | Africa, Sub Saharan | Age Factors | Population Characteristics | Demographic Factors | Population | Program Activities | Programs | Organization and Administration | HIV Infections | Viral Diseases | Diseases | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | HIV | Physiology | Biology Document Number: 331330 |
| 15. Peer Reviewed Title: Antiretroviral resistance patterns and HIV-1 subtype in mother-infant pairs after the administration of combination short-course zidovudine plus single-dose nevirapine for the prevention of mother-to-child transmission of HIV. Author: Chalermchockcharoenkit A; Culnane M; Chotpitayasunondh T; Vanprapa N; Leelawiwat W; Mock PA; Asavapiriyanont S; Teeraratkul A; McConnell MS; McNicholl JM; Tappero JW Source: Clinical Infectious Diseases. 2009 Jul 15;49(2):299-305. Abstract: BACKGROUND: World Health Organization guidelines for prevention of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) recommend administration of zidovudine and single-dose nevirapine (NVP) for HIV-1-infected women who are not receiving treatment for their own health or if complex regimens are not available. This study assessed antiretroviral resistance patterns among HIV-infected women and infants receiving single-dose NVP in Thailand, where the predominant circulating HIV-1 strains are CRF01_AE recombinants and where the minority are subtype B. METHODS: Venous blood samples were obtained from (1) HIV-infected women who received zidovudine from 34 weeks' gestation and single-dose NVP plus oral zidovudine during labor and (2) HIV-infected infants who received single-dose NVP after birth plus zidovudine for 4 weeks after delivery. HIV-1 drug resistance testing was performed using the TruGene assay (Bayer HealthCare). RESULTS: Most mothers and infants were infected with CRF01_AE. NVP resistance was detected in 34 (18%) of 190 women and 2 (20%) of 10 infants. There was a significantly higher proportion of NVP mutations in women with delivery viral loads of >50,000 copies/mL (adjusted odds ratio, 8.5; 95% confidence interval, 2.2-32.8, [Formula: see text] for linear trend) and in those with subtype B rather than CRF01_AE infections (38% vs. 16%; adjusted odds ratio, 3.6; 95% confidence interval, 1.1-11.8; P = .038). CONCLUSIONS: The lower frequency of NVP mutations among mothers infected with subtype CRF01_AE, compared with mothers infected with subtype B, suggests that individuals infected with subtype CRF01_AE may be less susceptible to the induction of NVP resistance than are individuals infected with subtype B. Language: English Keywords: DEVELOPING COUNTRIES | RESEARCH REPORT | WHO | MANUAL | STANDARDS | PREVENTION OF MOTHER-TO-CHILD TRANSMISSION | MOTHERS | INFANT | PERSONS LIVING WITH HIV/AIDS | HIV | DRUG RESISTANCE | ANTIRETROVIRAL DRUGS | ANTIRETROVIRAL THERAPY | TREATMENT | LABORATORY PROCEDURES | HIV TESTING | UN | International Agencies | Organizations | Political Factors | Sociocultural Factors | Research Methodology | Disease Transmission Control | Prevention and Control | Diseases | Parents | Family Relationships | Family Characteristics | Family and Household | Youth | Age Factors | Population Characteristics | Demographic Factors | Population | HIV Infections | Viral Diseases | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Laboratory Examinations and Diagnoses | Examinations and Diagnoses Document Number: 342429 |
| 16. Title: Age and height predict neuropathy risk in patients with HIV prescribed stavudine. Author: Cherry CL; Affandi JS; Imran D; Yunihastuti E; Smyth K; Vanar S; Kamarulzaman A; Price P Source: Neurology. 2009 Jul 28;73(4):315-20. Abstract: OBJECTIVE: Sensory neuropathy is a common problem in HIV-infected patients and is the dose-limiting toxicity of stavudine. Affordable methods of predicting neuropathy risk are needed to guide prescribing in countries where some use of stavudine remains an economic necessity. We therefore aimed to identify factors predictive of neuropathy risk before antiretroviral use. METHODS: A total of 294 patients attending clinics in Melbourne, Kuala Lumpur, and Jakarta were enrolled in a cross-sectional neuropathy screening program in 2006. Neuropathy was defined by the presence of symptoms and signs on the AIDS Clinical Trials Group Brief Peripheral Neuropathy Screen. Demographic, laboratory, and treatment details were considered as possible risk factors for neuropathy. The role of patient demographics in predicting stavudine neuropathy were then assessed in 181 patients who reported that they were free of neuropathy symptoms when first prescribed this drug. RESULTS: The prevalence of neuropathy was 42% in Melbourne (n = 100), 19% in Kuala Lumpur (n = 98), and 34% in Jakarta (n = 96). In addition to treatment exposures, increasing age (p = 0.002) and height (p = 0.001) were independently associated with neuropathy. Age and height cutoffs of > or=170 cm or > or =40 years predicted neuropathy. Among 181 patients who were asymptomatic before stavudine exposure, the risk of neuropathy following stavudine was 20% in younger, shorter patients, compared with 66% in older, taller individuals. CONCLUSIONS: Stavudine neuropathy risk increases with patient age and height. Prioritizing older and taller patients for alternative agents would be an inexpensive strategy to reduce neuropathy rates in countries where the burden of HIV disease limits treatment options. Language: English Keywords: INDIA | RESEARCH REPORT | CROSS SECTIONAL ANALYSIS | PERSONS LIVING WITH HIV/AIDS | SCREENING | NEUROLOGIC EFFECTS | TREATMENT | PRESCRIPTIONS | ANTIRETROVIRAL DRUGS | AGE FACTORS | BODY HEIGHT | Asia, Southern | Asia | Developing Countries | Research Methodology | HIV Infections | Viral Diseases | Diseases | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Physiology | Biology | Distributional Activities | Program Activities | Programs | Organization and Administration | Population Characteristics | Demographic Factors | Population Document Number: 342727 |
| 17. Peer Reviewed Title: In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. Author: Church JD; Mwatha A; Bagenda D; Omer SB; Donnell D; Musoke P; Nakabiito C; Eure C; Bakaki P; Matovu F; Thigpen MC; Guay LA; McConnell M; Fowler MG; Jackson JB; Eshleman SH Source: AIDS Research and Human Retroviruses. 2009 Jul;25(7):673-7. Abstract: Use of single dose nevirapine (sdNVP) to prevent HIV mother-to-child transmission is associated with the emergence of NVP resistance in many infants who are HIV infected despite prophylaxis. We combined results from four clinical trials to analyze predictors of NVP resistance in sdNVP-exposed Ugandan infants. Samples were tested with the ViroSeq HIV Genotyping System and a sensitive point mutation assay (LigAmp, for detection of K103N, Y181C, and G190A). NVP resistance was detected at 6-8 weeks in 36 (45.0%) of 80 infants using ViroSeq and 33 (45.8%) of 72 infants using LigAmp. NVP resistance was more frequent among infants who were infected in utero than among infants who were diagnosed with HIV infection after birth by 6-8 weeks of age. Detection of NVP resistance at 6-8 weeks was not associated with HIV subtype (A vs. D), pre-NVP maternal viral load or CD4 cell count, infant viral load at 6-8 weeks, or infant sex. NVP resistance was still detected in some infants 6-12 months after sdNVP exposure. In this study, in utero HIV infection was the only factor associated with detection of NVP resistance in infants 6-8 weeks after sdNVP exposure. Language: English Keywords: UGANDA | RESEARCH REPORT | CLINICAL TRIALS | INFANT | TREATMENT | HIV PREVENTION | ANTIRETROVIRAL DRUGS | DRUG RESISTANCE | PERSONS LIVING WITH HIV/AIDS | Africa, Eastern | Africa, Sub Saharan | Africa | Developing Countries | Clinical Research | Research Methodology | Youth | Age Factors | Population Characteristics | Demographic Factors | Population | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | HIV Infections | Viral Diseases | Diseases Document Number: 342890 |
| 18. Title: Access to medications and medical care after participation in HIV clinical trials: a systematic review of trial protocols and informed consent documents. Author: Ciaranello AL; Walensky RP; Sax PE; Chang Y; Freedberg KA; Weissman JS Source: HIV Clinical Trials. 2009 Jan-Feb;10(1):13-24. Abstract: BACKGROUND: Expectations regarding receipt of medications and medical care after clinical trials conclude may inform decisions about trial participation. We describe the frequency with which these posttrial services are described in the protocols and informed consent forms (ICFs) of antiretroviral drug (ARV) trials. METHOD: We systematically reviewed protocols and ICFs from Phase 3 and 4 antiretroviral trials in adults (> or = 12 years) from 1987 to 2006. Pharmaceutical industry-sponsored trials were selected from US Food and Drug Administration (FDA) documentation and Clinicaltrials.gov. Trials administered by the AIDS Clinical Trials Group (ACTG) were selected from the ACTG online registry. ACTG- and industry-provided protocols and ICFs were reviewed in full. The primary outcome was any mention of posttrial services, defined as any text regarding posttrial medications or medical care. RESULTS: Complete trial documents were available for 31 (48%) of 65 trials meeting inclusion criteria. Documents from 14 trials (45%) mentioned any posttrial service: 12 (39%) mentioned medications, and 5 (16%) mentioned medical care. Payment for trial participation (74%) and for care for trial-related injury (94%) were mentioned more often than were posttrial services. CONCLUSIONS: Posttrial medications or medical care was mentioned in the trial documents of <50% of reviewed antiretroviral trials. Improved efforts are needed to clearly describe posttrial services in clinical trial protocols and ICFs. Language: English Keywords: GLOBAL | RESEARCH REPORT | CLINICAL TRIALS | ADULTS | HUMAN VOLUNTEERS | ANTIRETROVIRAL DRUGS | INFORMED CONSENT | PARTICIPATION | ETHICS | ANTIRETROVIRAL THERAPY | PROGRAM ACCESSIBILITY | Clinical Research | Research Methodology | Age Factors | Population Characteristics | Demographic Factors | Population | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Social Behavior | Behavior | Sociocultural Factors | HIV | HIV Infections | Viral Diseases | Diseases | Program Evaluation | Programs | Organization and Administration Document Number: 341817 |
| 19. Peer Reviewed Title: [Antiretroviral drug supply in Argentina: National Program to Combat Human Retroviruses, AIDS, and STDs] Suministro de antirretrovirales en Argentina: Programa Nacional de Lucha contra Author: Colautti M; Luppi I; Salamano M; Traverso ML; Botta C; Palchik V Source: Revista Panamericana de Salud Pública / Pan American Journal of Public Health. 2009 Jan;25(1):62-8. Abstract: OBJECTIVES: To evaluate the supply cycle of antiretroviral (ARV) drugs, overseen by the National Program to Combat Human Retroviruses, AIDS, and STDs, through its order fulfillment indicators, and to obtain input from supply chain stakeholders. METHODS: A study was carried out from April-September 2005 in the pharmacies of two hospitals in Rosario, Argentina, involving both a quantitative analysis of indicators and secondary sources and a qualitative evaluation using semistructured interviews. RESULTS: The indicators reveal the impact that interruptions in ARV supply stream from the Program (central level) have and the overstocking that takes place at the pharmacies (local level) to manage the shortages. Changes in ARV treatment account for over 50% of the prescriptions. Fulfillments fall short of the reference value. The interviewees shared possible strategies for overcoming the communication gaps between levels, for building-up stock, for guaranteeing availability, and for shortening waiting times; reached informal agreements to deal with the lack of policies and the shortage of staff; acknowledged the challenges facing the jurisdictions (central, intermediate, and local/community); and recognized local efforts to improve management. CONCLUSIONS: These challenges could be the starting point for building teams to work on effectively decentralizing the entire supply chain and allowing the Program to fulfill its much-needed oversight role. Language: Spanish Keywords: ARGENTINA | RESEARCH REPORT | EVALUATION | EQUIPMENT AND SUPPLIES | LOGISTICS | AIDS | ANTIRETROVIRAL DRUGS | SEXUALLY TRANSMITTED DISEASES | TREATMENT | PRESCRIPTIONS | MANAGEMENT | South America, Southern | South America | Latin America | Americas | Developing Countries | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Organization and Administration | HIV Infections | Viral Diseases | Diseases | Reproductive Tract Infections | Infections | Distributional Activities | Program Activities | Programs Document Number: 341540 |
| 20. Title: Chronic viral hepatitis may diminish the gains of HIV antiretroviral therapy in sub-Saharan Africa. Author: Cooper CL; Mills E; Wabwire BO; Ford N; Olupot-Olupot P Source: International Journal of Infectious Diseases. 2009 May;13(3):302-6. Abstract: There is a heavy burden of HIV-hepatitis B virus (HBV) and HIV-hepatitis C virus (HCV) co-infection in many regions of the developing world. An often unmentioned illness, issues of poverty, socio-economic status, nutrition, access to medical care, and mistrust of Western-style medicine conspire to reduce the opportunity to receive clinical work-up and treatment for chronic viral hepatitis. We discuss key issues specific to the treatment of viral hepatitis and obstacles to success with this endeavor in the context of HIV co-infection in Africa. We predict that provision of viral hepatitis antiviral therapy will become a more pressing issue as more HIV-infected patients receive lifesaving combination antiretroviral therapy only to succumb thereafter from viral hepatitis-induced liver disease. Given the lessons learned from combination antiretroviral rollout in sub-Saharan Africa, establishing expertise and infrastructure for viral hepatitis care and antiviral therapy is relevant. Failure to act now may diminish the milestones and the gains made with antiretroviral therapy in the developing world. Language: English Keywords: AFRICA, SUB SAHARAN | CRITIQUE | ANTIRETROVIRAL THERAPY | ANTIRETROVIRAL DRUGS | SIDE EFFECTS | HEPATIC EFFECTS | TOXICITY | HEPATITIS | ANTIVIRAL DRUGS | OBSTACLES | SCREENING | Africa | Developing Countries | HIV | HIV Infections | Viral Diseases | Diseases | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Physiology | Biology | Drugs | Organization and Administration | Examinations and Diagnoses Document Number: 342111 |
| 21. Peer Reviewed Title: Establishment of drug-resistant HIV-1 in latent reservoirs. Author: Dahl V; Palmer S Source: Journal of Infectious Diseases. 2009 May 1;199(9):1258-60. Abstract: Language: English Keywords: DEVELOPING COUNTRIES | CRITIQUE | PERSONS LIVING WITH HIV/AIDS | MOTHERS | INFANT | ANTIRETROVIRAL DRUGS | ADMINISTRATION AND DOSAGE | DRUG RESISTANCE | ANTIRETROVIRAL THERAPY | PREVENTION OF MOTHER-TO-CHILD TRANSMISSION | IMMUNOLOGICAL EFFECTS | HIV Infections | Viral Diseases | Diseases | Parents | Family Relationships | Family Characteristics | Family and Household | Sociocultural Factors | Youth | Age Factors | Population Characteristics | Demographic Factors | Population | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Drugs | HIV | Disease Transmission Control | Prevention and Control | Immunity | Immune System | Physiology | Biology Document Number: 342358 |
| 22. Peer Reviewed Title: Two-months-off, four-months-on antiretroviral regimen increases the risk of resistance, compared with continuous therapy: A randomized trial involving West African adults. Author: Danel C; Moh R; Chaix ML; Gabillard D; Gnokoro J; Diby CJ; Toni T; Dohoun L; Rouzioux C; Bissagnene E; Salamon R; Anglaret X Source: Journal of Infectious Diseases. 2009 Jan 1;199(1):66-76. Abstract: A randomized trial was launched in Côte d'Ivoire in 2002 to compare continuous antiretroviral treatment (hereafter, "C-ART") to an ART regimen of 2 months off and 4 months on therapy (hereafter, "2/4-ART"). We report the final analysis. A total of 435 adults who were receiving successful ART ((median CD4 cell count prior to ART, 272 cells/mm3; 88% were receiving a zidovudine-lamivudine-efavirenz regimen) were randomized to receive C-ART or 2/4-ART. The main primary end point was the percentage of patients with <350 CD4 cells/mm3 at 24 months. The sample size ensured 80% power to demonstrate noninferiority (noninferiority bound, -15%), assuming that 30% of the patients in the C-ART arm would have <350 CD4 cells/mm3. Other end points were mortality, morbidity, cost of care, genotypic resistance, adherence, and toxicity. The percentage of patients with <350 CD4 cells/mm3 at 24 months was 5.6% (6 of 107) in the C-ART arm and 14.6% (46 of 315) in the 2/4-ART arm (lower bound of the 95% CI for the difference, -14%). Cost was 18% higher in the C-ART arm, and resistance to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was 20% higher in the 2/4-ART arm. Other end points were nonconclusive. Although 2/4-ART met the predetermined criteria for noninferiority, the percentage of patients with <350 CD4 cells/mm3 in the C-ART arm was lower than anticipated, which makes the clinical significance of this noninferiority uncertain. In addition, 2/4-ART led to an unacceptable additional risk of selecting for drug-resistant virus. This new argument against episodic ART strategies is also a caveat against any unplanned ART interruptions in Africa, where most patients receive NNRTIs. Language: English Keywords: COTE D'IVOIRE | RESEARCH REPORT | CLINICAL TRIALS | COMPARATIVE STUDIES | ADULTS | TIME FACTORS | ADMINISTRATION AND DOSAGE | RISK ASSESSMENT | DRUG RESISTANCE | ANTIRETROVIRAL DRUGS | IMMUNITY, CELLULAR | GENETICS | Developing Countries | Africa, Western | Africa, Sub Saharan | Africa | Clinical Research | Research Methodology | Studies | Age Factors | Population Characteristics | Demographic Factors | Population | Population Dynamics | Drugs | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Evaluation | Immunity | Immune System | Physiology | Biology Document Number: 328597 |
| 23. Peer Reviewed Title: (ARV-) Free State? The moratorium's threat to patients' adherence and the development of drug-resistant HIV [letter] Author: El-Khatib Z; Richter M Source: South African Medical Journal. 2009 Jun;99(6):412, 414. Abstract: This correspondence focuses on adherence to antiretrovirals (ARVs) in South Africa. It discusses factors that affect patient ability to access and adhere to ARVs including patient characteristics and context, ARV regimen, clinical situation, and the patient/health staff relationship. Language: English Keywords: SOUTH AFRICA | CRITIQUE | GOVERNMENT | PERSONS LIVING WITH HIV/AIDS | ANTIRETROVIRAL THERAPY | USER COMPLIANCE | ANTIRETROVIRAL DRUGS | DRUG RESISTANCE | RISK FACTORS | FUNDS | PROGRAM ACCESSIBILITY | HEALTH POLICY | Developing Countries | Africa, Southern | Africa, Sub Saharan | Africa | Political Factors | Sociocultural Factors | HIV Infections | Viral Diseases | Diseases | HIV | Behavior | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Financial Activities | Economic Factors | Program Evaluation | Programs | Organization and Administration | Policy Document Number: 342867 |
| 24. Title: Population pharmacokinetics of nevirapine in combination with rifampicin-based short course chemotherapy in HIV- and tuberculosis-infected South African patients. Author: Elsherbiny D; Cohen K; Jansson B; Smith P; McIlleron H; Simonsson US Source: European Journal of Clinical Pharmacology. 2009 Jan;65(1):71-80. Abstract: OBJECTIVE: The aim was to develop a model to describe the population pharmacokinetics of nevirapine in South African human immunodeficiency virus (HIV)-infected patients who were taking nevirapine-based antiretroviral therapy concomitantly or in the absence of rifampicin-based tuberculosis therapy. METHODS: Patients were divided into two groups: (1) patients receiving nevirapine-containing antiretroviral regimen (200 mg twice daily) and continuation phase rifampicin-containing tuberculosis therapy (n = 27) in whom blood samples were obtained before and not less than 14 days after they completed tuberculosis therapy; (2) patients without tuberculosis who were receiving a nevirapine-containing antiretroviral regimen for at least 3 weeks (n = 26). The population pharmacokinetics of nevirapine was described using nonlinear mixed effects modelling with NONMEM software. Based on the developed model, plasma concentration profiles after 300, 400 and 500 mg of nevirapine twice daily were simulated. RESULTS: Concomitant administration of rifampicin increased nevirapine oral clearance (CL/F) by 37.4% and reduced the absorption rate constant (k(a)) by almost sixfold. Rifampicin reduced the nevirapine average minimum concentration by 39%. Simulated doses of 300 mg twice daily elevated nevirapine concentrations above subtherapeutic levels in most patients, with minimum exposure above the recommended maximum concentration. The area under the concentration-time curve of 12-hydroxynevirapine was not different in the presence of rifampicin. 2-, 3- and 8-Hydroxynevirapine were not detectable (LLOQ = 0.025 mg/L). CONCLUSION: The developed model adequately describes nevirapine population pharmacokinetics in a South African population when taken with/and in the absence of rifampicin treatment. The simulations suggest that an increased dose of 300 mg twice daily would achieve adequate nevirapine concentrations in most patients during rifampicin-containing treatment for tuberculosis. Language: English Keywords: SOUTH AFRICA | RESEARCH REPORT | PERSONS LIVING WITH HIV/AIDS | TUBERCULOSIS | ANTIRETROVIRAL DRUGS | DRUG INTERACTIONS | TREATMENT | Africa, Southern | Africa, Sub Saharan | Africa | Developing Countries | Persons Living With HIV/AIDS | HIV Infections | Viral Diseases | Diseases | Infections | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Drugs Document Number: 330217 |
| 25. Peer Reviewed Title: The HIV-exposed, uninfected African child. Author: Filteau S Source: Tropical Medicine and International Health. 2009 Mar;14(3):276-87. Abstract: The increasing success of prevention of mother-to-child HIV transmission programmes means that in Africa, very large numbers of HIV-exposed, uninfected (HIV-EU) children are being born. Any health problems that these children may have will thus be of enormous public health importance, but to date have been largely neglected. There is some evidence that HIV-EU African children are at increased risk of mortality, morbidity and slower early growth than their HIV-unexposed counterparts. A likely major cause of this impaired health is less exposure to breast milk as mothers are either less able to breastfeed or stop breastfeeding early to protect their infant from HIV infection. Other contributing factors are parental illness or death resulting in reduced care of the children, increased exposure to other infections and possibly exposure to antiretroviral drugs. A broad approach for psychosocial support of HIV-affected families is needed to improve health of HIV-EU children. High quality programmatic research is needed to determine how to deliver such care. Language: English Keywords: AFRICA | CRITIQUE | LITERATURE REVIEW | EVALUATION | CHILDREN | PERSONS LIVING WITH HIV/AIDS | ORPHANS AND VULNERABLE CHILDREN | BREASTFEEDING | TIME FACTORS | CHILD HEALTH | GROWTH | DEFICIENCY DISEASES | CHILD MORTALITY | ANTIRETROVIRAL DRUGS | INFECTIONS | Developing Countries | Youth | Age Factors | Population Characteristics | Demographic Factors | Population | HIV Infections | Viral Diseases | Diseases | Family and Household | Sociocultural Factors | Infant Nutrition | Nutrition | Health | Population Dynamics | Child Development | Biology | Nutrition Disorders | Mortality | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care Document Number: 330961 |
| 26. Peer Reviewed Title: Rationing antiretroviral therapy in Africa--treating too few, too late. Author: Ford N; Mills E; Calmy A Source: New England Journal of Medicine. 2009 Apr 30;360(18):1808-10. Abstract: The past 6 years have seen striking advances in access to antiretroviral therapy in Africa. From 2002 onward, the international drive to scale up antiretroviral treatment gained considerable momentum, most notably with the establishment of the Global Fund to Fight AIDS, Tuberculosis, and Malaria, the "3 by 5" Initiative of the World Health Organization (WHO), and the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). The momentum has now begun to wane, with various groups arguing that the focus on AIDS has had its day and that health care funding should now be redirected to other areas, such as maternal and child health and primary care. But before the international community gives up on prioritizing care for patients with HIV infection, we believe that on-the-ground discussions must address not only whether enough has been done to scale up treatment but also whether the treatment that patients are receiving is good enough. The standard approach to HIV treatment in Africa is to wait until people are visibly sick, treat them with effective but poorly tolerated drugs, and then wait until they are sick again before switching regimens. There are several problems with this approach. The first is that too few people are receiving treatment. Second, we are waiting until people are symptomatic before they are treated. Another concern is that in most developing countries, patients are receiving drugs with major tolerability issues. Furthermore, not only should initial treatment begin earlier in developing countries, but when the first-line regimen fails, patients should also be switched earlier to another regimen. The drive to scale up antiretroviral treatment in Africa has encouraged a public health approach that promotes reaching the greatest number of patients with the simplest, most affordable regimens. We would argue that treating people when they are less sick with drugs that are less toxic and providing a simple tool for monitoring adherence and detecting treatment failure would be entirely consistent with this approach and would improve access to care by facilitating the decentralization of services from the hospital level to the clinic. (excerpt) Language: English Keywords: AFRICA | DEVELOPING COUNTRIES | SUMMARY REPORT | HIV INFECTIONS | ANTIRETROVIRAL THERAPY | TREATMENT | TIME FACTORS | SIGNS AND SYMPTOMS | DRUG RESISTANCE | ANTIRETROVIRAL DRUGS | SIDE EFFECTS | HIV TRANSMISSION | HEALTH POLICY | NEEDS ASSESSMENT | Viral Diseases | Diseases | HIV | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Population Dynamics | Demographic Factors | Population | Policy | Political Factors | Sociocultural Factors | Evaluation Document Number: 341021 |
| 27. Title: [A fixed dose anti-HIV combination for the poor? Triomune] Triom une: la tritherapie du pauvre ? Author: Garcia MV; Mukeba-Tshialala D; Vaira D; Moutschen M Source: Revue Medicale De Liege. 2009 Jan;64(1):32-6. Abstract: Despite a relative global stabilization of its incidence, HIV infection remains a major threat for public health, principally in Africa where it concerns more than 22 million people and constitutes the first cause of death on the continent. To face the emergency of the HIV/AIDS epidemics on the African continent, the primary goal is to make available to all patients free and efficient antiretroviral medications. Such a goal cannot be dissociated from large scale prevention campaigns. In 2000, Triomune, one of the first fixed dose combinations of three antiretrovirals (stavudine, lamivudine & nevirapine) was launched by the Indian drug company Cipla, specialized in the production of low cost medications. Its convenient pill burden (one pill twice a day) and its very low cost (around 30 US $ per month) make Triomune an appealing solution for the treatment of HIV/AIDS in Africa. Unfortunately, Triomune presents several drawbacks (low genetic barrier, frequent side effects) and one of its constituents is not used in Europe anymore. Other first line treatments are urgently needed. Language: French Keywords: AFRICA | RESEARCH REPORT | INCIDENCE | LOW INCOME POPULATION | PERSONS LIVING WITH HIV/AIDS | ANTIRETROVIRAL DRUGS | HIV INFECTIONS | FEES | NEEDS ASSESSMENT | PREVENTION AND CONTROL | TREATMENT | PROGRAM ACCESSIBILITY | Developing Countries | Measurement | Research Methodology | Social Class | Socioeconomic Status | Socioeconomic Factors | Economic Factors | Viral Diseases | Diseases | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Financial Activities | Evaluation | Program Evaluation | Programs | Organization and Administration Document Number: 341155 |
| 28. Peer Reviewed Title: [Pharmacy records as an indicator of non-adherence to antiretroviral therapy by HIV-infected patients] Utilizacao dos registros de dispensacao da farmacia como indicador da nao-adesao Author: Gomes RR; Machado CJ; Acurcio Fde A; Guimaraes MD Source: Cadernos De Saude Publica. 2009 Mar;25(3):495-506. Abstract: The objectives of this study were to evaluate anti-retroviral (ARV) prescription pickups during twelve months following the first prescription and to identify factors associated with irregular pickups or permanent dropout in two public HIV/AIDS referral centers in Belo Horizonte, Minas Gerais State, Brazil. Participants (n = 323) were antiretroviral naive and were recruited from May 2001 to May 2002. A total of 98 (30.3%) patients abandoned treatment, and 187 (57.9%) had at least one irregular pickup. Patients with irregular pickups and dropouts were compared to those with regular pickups. Multinomial multivariate analysis showed that living outside Belo Horizonte, CD4+ T-lymphocyte count greater than 200/mm(3), and antiretroviral regimen without protease inhibitors were associated with irregular pickups. In addition to these variables, not being on other medications, and any non-adherence recorded on patient charts were associated with treatment dropout. Pharmacy records are important potential indicators of non-adherence and should be incorporated as such in clinical practice. Strategies should be prioritized to reach out to dropouts or patients with irregular ARV pickups. Language: Portuguese Keywords: BRAZIL | RESEARCH REPORT | EVALUATION | PERSONS LIVING WITH HIV/AIDS | CLIENTS | DROPOUTS | USER COMPLIANCE | ANTIRETROVIRAL THERAPY | ANTIRETROVIRAL DRUGS | PRESCRIPTIONS | HIV INFECTIONS | TREATMENT | South America, Eastern | South America | Latin America | Americas | Developing Countries | Viral Diseases | Diseases | Program Activities | Programs | Organization and Administration | Behavior | HIV | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Distributional Activities Document Number: 342667 |
| 29. Peer Reviewed Title: Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. Author: Gottlieb GS; Badiane NM; Hawes SE; Fortes L; Toure M; Ndour CT; Starling AK; Traore F; Sall F; Wong KG; Cherne SL; Anderson DJ; Dye SA; Smith RA; Mullins JI; Kiviat NB; Sow PS Author: University of Washington-Dakar HIV-2 Study Group Source: Clinical Infectious Diseases. 2009 Feb 15;48(4):476-83. Abstract: BACKGROUND: The efficacy of various antiretroviral (ARV) therapy regimens for human immunodeficiency virus type 2 (HIV-2) infection remains unclear. HIV-2 is intrinsically resistant to the nonnucleoside reverse-transcriptase inhibitors and to enfuvirtide and may also be less susceptible than HIV-1 to some protease inhibitors (PIs). However, the mutations in HIV-2 that confer ARV resistance are not well characterized. METHODS: Twenty-three patients were studied as part of an ongoing prospective longitudinal cohort study of ARV therapy for HIV-2 infection in Senegal. Patients were treated with nucleoside reverse-transcriptase inhibitor (NRTI)- and PI (indinavir)-based regimens. HIV-2 pol genes from these patients were genotyped, and the mutations predictive of resistance in HIV-2 were assessed. Correlates of ARV resistance were analyzed. RESULTS: Multiclass drug-resistance mutations (NRTI and PI) were detected in strains in 30% of patients; 52% had evidence of resistance to at least 1 ARV class. The reverse-transcriptase mutations M184V and K65R, which confer high-level resistance to lamivudine and emtricitabine in HIV-2, were found in strains from 43% and 9% of patients, respectively. The Q151M mutation, which confers multinucleoside resistance in HIV-2, emerged in strains from 9% of patients. HIV-1-associated thymidine analogue mutations (M41L, D67N, K70R, L210W, and T215Y/F) were not observed, with the exception of K70R, which was present together with K65R and Q151M in a strain from 1 patient. Eight patients had HIV-2 with PI mutations associated with indinavir resistance, including K7R, I54M, V62A, I82F, L90M, L99F; 4 patients had strains with multiple PI resistance-associated mutations. The duration of ARV therapy was positively associated with the development of drug resistance (P = .02). Nine (82%) of 11 patients with HIV-2 with detectable ARV resistance had undetectable plasma HIV-2 RNA loads (<1.4 log(10) copies/mL), compared with 3 (25%) of 12 patients with HIV-2 with detectable ARV resistance (P = .009). Patients with ARV-resistant virus had higher plasma HIV-2 RNA loads, compared with those with non-ARV-resistant virus (median, 1.7 log(10) copies/mL [range, <1.4 to 2.6 log(10) copies/mL] vs. <1.4 log(10) copies/mL [range, <1.4 to 1.6 log(10) copies/mL]; P = .003). CONCLUSIONS: HIV-2-infected individuals treated with ARV therapy in Senegal commonly have HIV-2 mutations consistent with multiclass drug resistance. Additional clinical studies are required to improve the efficacy of primary and salvage treatment regimens for treating HIV-2 infection. Language: English Keywords: SENEGAL | RESEARCH REPORT | LONGITUDINAL STUDIES | CLIENTS | PERSONS LIVING WITH HIV/AIDS | ANTIRETROVIRAL DRUGS | DRUG RESISTANCE | ANTIRETROVIRAL THERAPY | AIDS | IMMUNOLOGICAL EFFECTS | Developing Countries | Africa, Western | Africa, Sub Saharan | Africa | Studies | Research Methodology | Program Activities | Programs | Organization and Administration | HIV Infections | Viral Diseases | Diseases | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | HIV | Immunity | Immune System | Physiology | Biology Document Number: 342643 |
| 30. Peer Reviewed Title: The obstetric face and challenge of HIV/AIDS. Author: Guidozzi F; Black V Source: Clinical Obstetrics and Gynecology. 2009 Jun;52(2):270-84. Abstract: The human immunodeficiency virus (HIV) pandemic is one of the most serious health crises facing the world. Of the estimated 33.2 million people living with HIV worldwide, 22.5 million (68%) live in Sub-Saharan Africa, where women of childbearing age are most severely affected. Children primarily acquire HIV infection through mother-to-child transmission. Despite recent encouraging success, low-income countries have not been able to effectively curtail transmission of HIV to the infant during or after pregnancy, resulting in about 90% of the estimated 420,000 newly infected children per annum occurring in Sub-Saharan Africa. Language: English Keywords: DEVELOPING COUNTRIES | CRITIQUE | RECOMMENDATIONS | HIV INFECTIONS | AIDS | EPIDEMICS | OBSTETRICS | PREVENTION OF MOTHER-TO-CHILD TRANSMISSION | BREASTFEEDING | HIV TESTING | ANTIRETROVIRAL THERAPY | ANTIRETROVIRAL DRUGS | ADMINISTRATION AND DOSAGE | DRUG RESISTANCE | Viral Diseases | |