Dr. J.R. ALBANI is requiring young researchers to submit IEF or IIF Marie Curie Fellowships (deadline 14 august 2007) Dr. J. R. Albani, Head of the Laboratoire de Biophysique Moléculaire (University of Lille 1, France) wishes to recruit a fellow researcher for a period of two years. Dr Albani, a specialist of fluorescence spectroscopy and of proteins structure and dynamics, has bought re
UntitledExperience with the use of a first-line regimen ofstavudine, lamivudine and nevirapine in patients in theTREAT Asia HIV Observational Database J Zhou,1 NI Paton,2 R Ditangco,3 Y-MA Chen,4 A Kamarulzaman,5 N Kumarasamy,6 CKC Lee,7 PCK Li,8 TP Merati,9P Phanuphak,10 S Pujari,11 A Vibhagool,12 F Zhang,13 J Chuah,14 KR Frost,15 DA Cooper1 and MG Law1 on behalf ofthe TREAT Asia HIV Observational Database1National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, Australia, 2TanTock Seng Hospital, Singapore, 3Research Institute for Tropical Medicine, Manila, Philippines, 4AIDS Prevention andResearch Centre, National Yang-Ming University, Taipei, Taiwan, 5University of Malaya, Kuala Lumpur, Malaysia, 6YRGCentre for AIDS Research and Education, Chennai, India, 7Hospital Kuala Lumpur, Kuala Lumpur, Malaysia, 8QueenElizabeth Hospital, Hong Kong, China, 9School of Medicine, Udayana University & Sanglah Hospital, Denpasar, Bali,Indonesia, 10HIV-NAT/The Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 11HIV Project, Ruby Hall Clinic, Pune,India, 12Ramathibodi Hospital, Bangkok, Thailand, 13Beijing Ditan Hospital, Beijing, China, 14Gold Coast Sexual HealthClinic, Miami, Qld, Australia, 15American Foundation for AIDS Research, New York, NY, USA BackgroundThe antiretroviral treatment (ART) combination of stavudine, lamivudine and nevirapine (d4T/3TC/NVP) is the most frequently used initial regimen in many Asian countries. There are few data on theoutcome of this treatment in clinic cohorts in this region.
MethodsWe selected patients from the TREAT Asia HIV Observational Database (TAHOD) who started theirfirst ART regimen with d4T/3TC/NVP. Treatment change was defined as cessation of therapy or theaddition or change of one or more drugs. Clinical failure was defined as diagnosis with an AIDS-defining illness, or death while on d4T/3TC/NVP treatment.
ResultsThe rate of treatment change among TAHOD patients starting d4T/3TC/NVP as their first antiretroviraltreatment was 22.3 per 100 person-years, with lower baseline haemoglobin (i.e. anaemia) associatedwith slower rate of treatment change. The rate of clinical failure while on d4T/3TC/NVP treatment was7.3 per 100 person-years, with baseline CD4 cell count significantly associated with clinical failure.
After d4T/3TC/NVP was stopped, nearly 40% of patients did not restart any treatment and, of those whochanged to other treatment, the majority changed to zidovudine (ZDV)/3TC/NVP and less than 3% ofpatients changed to a protease inhibitor (PI)-containing regimen. The rates of disease progression on thesecond-line regimen were similar to those on the first-line regimen.
ConclusionThese real-life data provide an insight into clinical practice in Asia and the Pacific region. d4T/3TC/NVP is maintained longer than other first-line regimens and change is mainly as a result of adverseeffects rather than clinical failure. There is a need to develop affordable second-line antiretroviraltreatment options for patients with HIV infection in developing countries.
Keywords: adverse effects, antiretroviral treatment, Asia-Pacific region, stavudine/lamivudine/nevirapine, treatment change Received: 11 October 2005, accepted 10March 2006 Correspondence: Mr Jialun Zhou, National Centre in HIV Epidemiology andClinical Research, The University of New South Wales, Level 2, 376 VictoriaStreet, Darlinghurst, Sydney, NSW 2010, Australia. Tel: 1 612 93850900;fax: 1 612 93850920; e-mail: email@example.com First-line treatment of d4T/3TC/NVP in TAHOD 9 subtype, and date and result of hepatitis B virus, hepatitis Cvirus and syphilis serology; (2) stage of disease: CD4 and The combination of stavudine, lamivudine and nevirapine CD8 cell count, HIV viral load estimation, prior AIDS- (d4T/3TC/NVP) is the most popular combination currently defining illness, and date and cause of death; (3) treatment in use in many Asian countries because the individual history: prior and current prescribed antiretroviral treat- drugs are available as generics and also in a convenient ments, reason for treatment changes (e.g. treatment failure, clinical failure and adverse events) and prophylactic widely used, the regimen has some theoretical disadvan- treatments for opportunistic infection.
tages. d4T and NVP do not have the optimal toxicity profile A modified version of the 1993 Centers for Disease of drugs within their class . Furthermore, 3TC and NVP Control and Prevention (CDC) AIDS case definition  was have a low genetic barrier to resistance and failure adopted, in which a presumptive diagnosis was available may involve and compromise further treatment with for most illnesses. All data were entirely observational, with test or intervention performed only according to the nucleotide reverse transcriptase inhibitors (NRTIs) and clinical guideline at each site. It was also noted that the nonnucleoside reverse transcriptase inhibitors (NNRTIs)].
laboratory methods varied across the sites. For example, The third class of drugs, protease inhibitors (PIs), are HIV viral load estimations were obtained using a Roche expensive, and hence the management of patients who fail Amplicor monitor (Roche Molecular Systems Inc., Branch- this regimen may be especially challenging in resource- burg, NJ, USA) or Quantiplex bDNA assay (Chiron Diagnostics, East Walpole, MA, USA).
In spite of the widespread adoption of this regimen in Patients who started their first ARV combination with antiretroviral therapy (ART) scale-up programmes, there is d4T/3TC/NVP were included in the study. Because of the a paucity of published data on the use and outcome of this limited number of patients who initiated treatment with regimen in real-life clinical settings outside that of d4T/3TC/NVP after recruitment to TAHOD, analysis was randomized controlled trials. Information about how well carried out on both retrospective and prospective data.
the regimen is tolerated and sustained in clinical practice is essential for evaluating the likely success of large-scale Treatment change: either stopping the d4T/3TC/NVP treatment programmes, and for understanding the magni- combination, or any addition or change of at least one tude of the need for second-line therapy or alternative drug. Follow-up was censored at the time of treatment drugs. The TREAT Asia HIV Observational Database change or death, or at the date of most recent data (TAHOD) is a collaborative study by the TREAT Asia network, a co-operative network of clinicians throughout Clinical failure: diagnosis with an AIDS-defining Asia and the Pacific, funded by the American Foundation illness, or death while on d4T/3TC/NVP treatment.
of AIDS Research (amfAR) . In this study, we describe the Follow-up was censored at the time of clinical failure rate of treatment change among patients taking d4T/3TC/ while on treatment, or at the time of treatment change.
NVP in TAHOD and determine factors associated with d4T/ Virological failure: while on d4T/3TC/NVP treatment, 3TC/NVP treatment change. We also describe the spectrum an HIV viral load measurement of 4 400 HIV-1 RNA of first regimen changes selected after d4T/3TC/NVP copies/mL, obtained at least 6 months after treatment change and examine the outcome with the second-line was started. Follow-up was censored at virological failure, or at the time of treatment change.
Immunological failure: while on d4T/3TC/NVP treat- ment, three successive decreasing CD4 cell counts (thefirst obtained at least 6 months after treatment was TAHOD is a collaborative observational cohort study started). Follow-up was censored at immunological involving 12 sites in the Asia and Pacific region (see the failure or at the time of treatment change.
Appendix). Detailed methods are published elsewhere , Clinical failure after first treatment change: diagnosis but briefly, each site recruited 200 patients, both treated with an AIDS-defining illness or death after d4T/3TC/ and untreated with antiretroviral (ARV) drugs. Recruitment NVP was stopped. Follow-up was censored at the time was based on a consecutive series of patients regularly of AIDS or death, or at the date of most recent data attending a given site from a particular start-up time.
The following data were collected: (1) patient demo- Rate of treatment change, and clinical, virological and graphics: date of the clinical visit, age, gender, ethnicity, immunological failures were measured using the person- exposure category, date of first positive HIV test, HIV-1 time method. Factors associated with treatment change and r 2007 British HIV Association HIV Medicine (2007) 8, 8–16 Table 1 Type of first antiretroviral treatment, by year in which treatment started *3 1 (NRTI Æ PI – NNRTI), three or more drugs including at least one nucleoside reverse transcriptase inhibitor (NRTI) and/or a protease inhibitor (PI), butwithout a nonnucleoside reverse transcriptase inhibitor (NNRTI).
w3 1 (NRTI 1 NNRTI – PI), three or more drugs including at least one NNRTI, but without a PI.
z3 1 (NNRTI 1 PI Æ NRTI), three or more drugs including at least one NNRTI and one PI, with or without an NRTI.
d4T, stavudine; 3TC, lamivudine; NVP, nevirapine; ZDV, zidovudine.
clinical failure were assessed by univariate and multi- ARV treatment with d4T/3TC/NVP, which has been the major NNRTI-based treatment since 2002, with nearly half models. Covariates included in the analysis were demo- of all patients receiving the treatment. Treatment change graphics, time since HIV diagnosis, clinical disease at time of ART start, CD4 cell count and viral load prior to Among the 404 patients who started d4T/3TC/NVP as their initiation of ART, nutritional status (body mass index), first antiretroviral treatment, there were 131 patients who hepatitis B and C virus infection status, and haemoglobin stopped the combination over a total of 586.9 person- level. Multivariate models were built using forward years, a rate of 22.3 [95% confidence interval (CI) 18.8– stepwise techniques. Statistical significance was taken as 26.5] per 100 person-years. The median duration of d4T/ 3TC/NVP treatment among the patients who stopped was262 days (range 2–1519 days). The rate of treatment change of d4T/3TC/NVP was compared with that of otherinitial ARV regimens (Table 2, Fig. 1). Monotherapy and From September 2003 to 15 October 2004, 2088 patients double therapy had the highest rate of treatment change, were recruited to TAHOD. A total of 1702 patients were with almost all patients stopping within a year. The rate of treated with ARV drugs (Table 1). The proportion of treated change was lower in treatment with NNRTI-based triple or patients receiving monotherapy or double therapy de- more combination therapy than in treatment with PI-based creased from 72% before 2000 to around 10% in recent treatment, or in treatment containing three or more NRTIs.
years. From 2000 onwards, the majority of treated patients Treatment with d4T/3TC/NVP showed a lower rate of started with a NNRTI-based treatment combination, with change than treatment with most other NNRTI-based three or more drugs containing at least one NNRTI and at least one NRTI, but without a PI. A total of 404 patients Baseline haemoglobin was the only significant risk (23.7% of all patients starting their first treatment) started factor associated with treatment change, with patients r 2007 British HIV Association HIV Medicine (2007) 8, 8–16 First-line treatment of d4T/3TC/NVP in TAHOD 11 Table 2 Rate of change of first antiretroviral treatment *Excluding d4T/3TC/NVP.
CI, confidence interval; d4T, stavudine; 3TC, lamivudine; NVP, nevirapine; ZDV, zidovudine; EFV, efavirenz; ddI, didanosine; NRTI, nucleoside reversetranscriptase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
who were anaemic when d4T/3TC/NVP was started having a longer duration on this treatment (Table 3).
Table 4 summarizes the reasons for d4T/3TC/NVP treat- ment change and duration of treatment. Adverse effects (62.6% of patients stopped d4T/3TC; 20.3% of the 404patients included in the study) were the major reason for treatment change, among which lipodystrophy was the most common, followed by hepatitis, rash and peripheral neuro-pathy. Drug interaction was not reported as a reason for treatment change. There were large variations of duration on treatment before the treatment change. Clinical failure: Among the 404 patients who started d4T/3TC/NVP as their Fig. 1 Duration of first antiretroviral treatment. d4T, stavudine; 3TC,lamivudine; NVP, nevirapine; NRTI, nucleoside reverse transcriptase first antiretroviral treatment, two patients died and 38 inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; patients developed AIDS during treatment over 547.7 HAART, highly active antiretroviral therapy; PI, protease inhibitor; person-years of follow-up, giving a rate of clinical failure of 7.3 per 100 person-years (95% CI 5.4–10.0). The majorityof newly diagnosed AIDS cases after treatment were a result patients had an HIV viral load of more than 400 copies/mL of tuberculosis (39.5%), followed by cytomegalovirus retinitis while on treatment (over 132.3 person-years), giving a rate (15.8%), extrapulmonary cryptococcosis (10.5%) and tox- of 3.7 per 100 person-years (95% CI 1.6–9.1). There were 56 oplasmosis (10.5%). Baseline CD4 cell count was significantly patients who had at least three CD4 cell counts 6 months associated with disease progression (data not shown).
after starting d4T/3TC/NVP. During the period of d4T/3TC/ Among the 38 patients who had an AIDS diagnosis, 13 NVP treatment (over 148.5 person-years), 10 patients had stopped d4T/3TC/NVP at various stages, but none of these three consecutive decreasing CD4 cell counts, giving a rate 13 patients stopped d4T/3TC/NVP because of the AIDS of 6.7 per 100 person-years (95% CI 3.6–12.5).
diagnosis, which was defined as an endpoint in the Most of these patients either did not stop d4T/3TC/NVP analysis. Reported reasons for stopping varied from the treatment because of the virological or immunological patient’s decision to adverse effects or clinical failure at a failure, or stopped long after the failure, with the reasons later stage (nearly 1 year after the AIDS diagnosis).
for treatment change mainly not related to virologicalfailure (data not shown). Adverse effects (mainly lipody-strophy) were again the major reason for treatment change.
Virological and immunological failure (among patientswith a viral load or CD4 cell measurement after startingd4T/3TC/NVP) There were 57 patients who had at least one HIV viral load Table 5 summarizes the ARV treatment used after d4T/3TC/ assessment 6 months after starting d4T/3TC/NVP. Five NVP was stopped and the duration on d4T/3TC/NVP before r 2007 British HIV Association HIV Medicine (2007) 8, 8–16 Table 3 Predictors of treatment change among patients starting stavudine/lamivudine/nevirapine (d4T/3TC/NVP) as their first antiretroviraltreatment Time between HIV treatment and treatment initiation (years) HIV viral load prior to treatment (copies/mL) wCD4 count measured within 180 days before treatment started; HIV viral load measured within 365 days before treatment started.
zBody mass index (BMI) 5 weight (kg)/[height (m)]2: Underweight, BMI o 18.5; normal, BMI 18.5–24.9; overweight, BMI425.0.
§Hepatitis B virus infection: a positive hepatitis B surface antigen (HBsAg) test; hepatitis C virus infection: a positive anti-hepatitis C virus antibody test.
zHaemoglobin tested within 180 days before treatment started. Definition of anaemia: normal, haemoglobin413 g/dL for male and 12 g/dL for femalesubjects; anaemia, 8–13 g/dL for male and 8–12 g/dL for female subjects; severe anaemia, o8 g/dL for both male and female subjects.
CI, confidence interval; HR, hazard ratio.
r 2007 British HIV Association HIV Medicine (2007) 8, 8–16 First-line treatment of d4T/3TC/NVP in TAHOD 13 Table 4 Reasons for stavudine/lamivudine/nevirapine (d4T/3TC/NVP) Table 5 Antiretroviral treatment after stavudine/lamivudine/nevira- treatment change and duration of treatment pine (d4T/3TC/NVP) stopped and duration on d4T/3TC/NVP beforetreatment changed *As a percentage of the total number of patients who changed treatment for a specific reason (in the second column).
ABC, abacavir; ddI, didanosine; EFV, efavirenz; IDV, indinavir; RTV, ritonavir; stopping. Nearly 40% of the 131 patients stopped taking any treatment, at least for some period of time. Amongthose who changed to other treatment, the majoritychanged to zidovudine (ZDV)/3TC/NVP. Only three patients(o 3%) changed to a combination containing a PI.
The major reason for treatment change among those patients who changed to ZDV/3TC/NVP was adverse effects Initial treatment with two NRTIs and one NNRTI is (86%, Po0.001), over half of which were lipodystrophy recommended by the World Health Organization (WHO) (52%), followed by peripheral neuropathy (20%) and lactic , as part of the ‘3 by 5’ strategy against HIV and AIDS .
acidosis (14%). Patients who changed to ZDV/3TCNVP had Nearly one in four of the TAHOD patients started their ARV remained on d4T/3TC/NVP for a significantly longer time treatment with d4T/3TC/NVP. Data on whether the drug (median 469 days; range 5–1398 days) than had the was generic or proprietary was not collected. However, patients who changed to treatment other than ZDV/3TC/ in Asian countries such as India [1,2] and Thailand , NVP after stopping d4T/3TC/NVP (median 79 days; range the generic d4T/3TC/NVP combination, or GPO-VIR in Thailand, is the most popular combination currently in use.
A total of 20 patients developed AIDS and three died In this study, the rate of treatment change among (one patient died with an AIDS diagnosis on the same day) TAHOD patients starting d4T/3TC/NVP as the first ARV after stopping d4T/3TC/NVP, over a total of 152.0 person- treatment was found to be 22.3 per 100 person-years. The years of follow up, giving a rate of clinical failure of 14.5 rate of d4T/3TC/NVP treatment change was comparable to per 100 person-years (95% CI 9.5–22.0). Patients receiving that seen in other studies. Using data from the Australia ZDV/3TC/NVP after stopping d4T/3TC/NVP had a lower HIV Observational Database (AHOD), Petoumenos et al.  rate of clinical failure than patients receiving no treatment reported a rate of treatment change of 31% among patients (3.8 vs 27.3 per 100 person-years; P 5 0.004).
who started their first NNRTI-based HAART combination.
r 2007 British HIV Association HIV Medicine (2007) 8, 8–16 In the OzCombo 2 Study , 27% of the patients on d4T/ acidosis and peripheral neuropathy, may have been 3TC/NVP did not complete treatment over a 52-week underestimated in this study, whereas early toxicities, such clinical trial. In a study in India , among patients as hepatitis, rash and pancreatitis, may mainly have been receiving a generic NVP-based HAART regimen (55% of captured. The prevalence of treatment-related hepatitis them receiving NVP in combination with d4T/3TC), 16% (2.5% of all patients receiving d4T/3TC/NVP) was similar to stopped treatment. The substantial rate of change is of that found in a clinical trial setting in Thailand (5.8%)  concern given the very limited options available in some and in observational studies in India (3.2%)  and settings in TAHOD, as many people who stop actually do Thailand (7%) . However, without liver enzyme mon- not have a viable alternative treatment regimen. This also itoring for all patients receiving treatment, this prevalence shows that a one-combination-fits-all policy is potentially may be underestimated. The prevalence of lipodystrophy going to deprive a substantial number of patients of was low compared with prevalences for Western cohorts effective long-term therapy. In AHOD, patients with a (38–50% [3,12,13]) but similar to those for other Asian baseline CD4 count ofo200 cells/mL had an earlier patient populations [14,15]. This may reflect the fact that treatment change, while in this study a lower baseline lipodystrophy is less common among nonwhite patients, haemoglobin level (i.e. anaemia) was associated with a later and also the small proportion of patients receiving PI- treatment change. This association with anaemia may be explained by the fact that the common alternative drug, The rate of clinical failure while on d4T/3TC/NVP ZDV, is contraindicated in patients with anaemia. Hence treatment and the relationship between baseline CD4 cell there might be greater reluctance to change d4T/3TC/NVP count and disease progression are similar to findings therapy in anaemic patients because there are few effective obtained in other studies [1,8,16,17]. It is possible that some of the events may have represented immune The rate of treatment change was lower among patients reconstitution syndrome. In a cohort of patients receiv- starting d4T/3TC/NVP than among patients initiating most ing fixed-dose combination therapy in India, 67% of other NNRTI-based triple or more combination therapies, a clinical events were defined as immune reconstitution PI-based regimen or a triple combination containing only NRTI. Similar to AHOD, patients receiving NNRTI-based The rate of virological and immunological failure after 6 HAART treatment had a slower change rate than patients months of treatment was consistent with the findings of receiving PI-based treatment. Because of the small number previous studies [8,16], although relatively few patients of patients who were receiving PI-based treatment, further had measurements taken. It is interesting that neither comparison was not performed. The reason for a higher disease progression nor virological or immunological change rate for PI-based regimens might be toxicity  or failure was a major reason for treatment change, as the unsustainable expense for some patients.
patients generally continued their treatment after failure.
In this study, the main reported reason for d4T/3TC/NVP When they finally stopped the regimen, it was mainly treatment change was adverse effects, this reason being because of adverse effects. Another point worth noting recorded for 20% of the 404 patients initiating d4T/3TC/ is the relative paucity of data for HIV viral load and CD4 NVP and 62.6% of the 131 patients who stopped d4T/3TC/ cell count change among patients receiving treatment, NVP. In a study with a relatively short follow-up time of 24 although TAHOD participating sites are by and large the weeks in treatment-naı¨ve patients receiving a fixed-dosed better academic centres in the region. It is clear that many combination of d4T/3TC/NVP in Thailand , 20% patients are managed without regular viral load and CD4 experienced adverse events and 15% withdrew from the cell count monitoring, and yet seem to have similar rates study because of the adverse events. Side effects were also of survival and response to treatment to patients who do the major reason for discontinuing HAART treatment in receive such monitoring [4,17]. This shows that limitations Indian patients (64% of patients who discontinued a in laboratory monitoring should not necessarily impede generic HAART regimen) . Although lactic acidosis and implementation of ART. However, the fact that early failure lipodystrophy were not observed during this 24-week is not being detected in these patients by laboratory study, this is consistent with our observation that these are monitoring and the fact that treatment is maintained even late events: the median duration on treatment for patients in the patients in whom such failure is being detected who stopped because of lactic acidosis was 416 (range 204– suggest that many of these patients are likely to develop 951) days and that for lipodystrophy was 546 (30–1519) extensive resistance by the time a treatment change finally days. Given the relatively short period of follow up in TAHOD, the true prevalence of adverse effects leading to After d4T/3TC/NVP was stopped, nearly 40% of patients long-term treatment change, such as lipodystrophy, lactic ceased ART entirely. Among those who changed to other r 2007 British HIV Association HIV Medicine (2007) 8, 8–16 First-line treatment of d4T/3TC/NVP in TAHOD 15 treatment, the majority changed to ZDV/3TC/NVP. This well create extensive problems with resistance in the change is unlikely to be a result of early toxicity and is more likely to reflect a concern to avoid future lipodystro-phy. When a cheap fixed-dose combination containing ZDV/3TC/NVP becomes more widely available, it is likelythat this will be frequently used as the initial regimen TREAT Asia and TAHOD are funded by a grant from the because of this concern to avoid lipodystrophy. Only three American Foundation for AIDS Research. The National patients changed to a combination containing PI. This may Centre in HIV Epidemiology and Clinical Research is also reflect the limited choice of treatment among patients funded by the Australian Government Department of in the Asia and Pacific region. The rates of progression on Health and Ageing, and is affiliated with the Faculty of the second-line regimen were similar to those on the first- Medicine, The University of New South Wales.
line regimen, further confirming that patients who changedwere probably not failing the first-line regimen, but changed mainly because of toxicity concerns.
Several limitations should be taken into consideration 1 Kumarasamy N, Solomon S, Chaguturu SK et al. The safety, when interpreting the results. Firstly, the analysis was tolerability and effectiveness of generic antiretroviral drug performed on both prospective and retrospective data. With regimens for HIV-infected patients in south India. AIDS 2003; data transfer each year, increasing amounts of prospective data will be available for better understanding of the 2 Pujari SN, Patel AK, Naik E et al. Effectiveness of generic fixed- efficacy and side effects of the d4T/3TC/NVP regimen and dose combinations of highly active antiretroviral therapy for other treatment combinations. Secondly, the TAHOD treatment of HIV infection in India. J Acquir Immune Defic patients, who are recruited if they have ‘good’ follow-up based on clinicians’ judgement, cannot be seen as entirely 3 Carr A, Cooper DA. Adverse effects of antiretroviral therapy.
representative of HIV-infected patients in the Asia–Pacific region. However, studies on the natural history of HIV 4 Zhou J, Kumarasamy N, Ditangco R et al. The TREAT Asia HIV disease and responses to ARV treatment can still be derived Observational Database: baseline and retrospective data.
from a cohort of TAHOD patients with good follow up, J Acquir Immune Defic Syndr 2005; 38: 174–179.
albeit with some limitations on the generalizability of the 5 Centers for Disease Control and Prevention. 1993 revised findings. Thirdly, although the overall follow-up rate is classification system for HIV infection and expanded satisfactory (up to 90%), loss to follow-up must be surveillance case definition for AIDS among adolescents and considered when interpreting the results. AIDS or adverse adults. MMWR Recomm Rep 1992; 41: 1–19.
effects might be underreported if a patient does not 6 World Health Organization. Scaling Up Antiretroviral Therapy regularly visit the clinics or if a patient dies. Efforts have in Resource-limited Settings. Treatment Guidelines for a Public been made to maximize follow-up, with each site devel- Health Approach – 2003 Revision. Geneva, Switzerland: World oping its own mechanism to contact patients whenever 7 WHO/UNAIDS. Treating 3 Million by 2005: Making It Happen In summary, our study presents real-life data providing an insight into clinical practice in Asia and the Pacific 8 Anekthananon T, Ratanasuwan W, Techasathit W, Sonjai A, region. It confirms the findings of earlier studies in African Suwanagool S. Safety and efficacy of a simplified fixed- and Asian countries that have shown treatment with the dose combination of stavudine, lamivudine and nevirapine simple fixed-dose combination of d4T/3TC/NVP to be safe (GPO-VIR) for the treatment of advanced HIV-infected and effective, with good adherence and tolerability patients: a 24-week study. J Med Assoc Thai 2004; 87: [1,2,8,16]. It is of concern that there is a lack of systematic laboratory monitoring, together with very limited options 9 The Australian HIV Observational Database. Rates of for treatment changes, other than those implemented for combination antiretroviral treatment change in Australia, side effects. It is also notable that adverse events are the 1997–2000. HIV Med 2002; 3: 28–36.
most common reported reason for treatment change. As 10 French M, Amin J, Roth N et al. Randomized, open-label, toxicity is likely to remain a problem, there is a need to comparative trial to evaluate the efficacy and safety of three develop affordable second-line ART options for patients antiretroviral drug combinations including two nucleoside with HIV infection in developing countries. Although d4T/ analogues and nevirapine for previously untreated HIV-1 3TC/NVP appears to be relatively well tolerated by the Infection: the OzCombo 2 study. HIV Clin Trials 2002; 3: majority of patients, the current practice of treatment may r 2007 British HIV Association HIV Medicine (2007) 8, 8–16 11 Law WP, Dore GJ, Duncombe CJ et al. Risk of severe hepato- Zhang*, H. Zhao and N. Han, Beijing Ditan Hospital, toxicity associated with antiretroviral therapy in the HIV-NAT Beijing, China; P. Li* and M. P. Lee, Queen Elizabeth Cohort, Thailand, 1996–2001. AIDS 2003; 17: 2191–2199.
Hospital, Hong Kong, China; N. Kumarasamy* and J. A.
12 Carr A, Samaras K, Burton S et al. A syndrome of peripheral Cecelia, YRG Centre for AIDS Research and Education, lipodystrophy, hyperlipidaemia and insulin resistance in Chennai, India; S. Pujari* and K. Joshi, HIV Project, Ruby patients receiving HIV protease inhibitors. AIDS 1998; 12: Hall Clinic, Pune, India; T. P. Merati* and F. Yuliana, Faculty of Medicine, Udayana University & Sanglah 13 Carr A. HIV protease inhibitor-related lipodystrophy syndrome.
Hospital, Bali, Indonesia; S. Oka* and M. Honda, Interna- Clin Infect Dis 2000; 30 (Suppl. 2): S135–S142.
tional Medical Centre of Japan, Tokyo, Japan; C. K. C. Lee* 14 Chang KH, Kim JM, Song YG, Hong SK, Lee HC, Lim SK.
and J. Pang, Hospital Kuala Lumpur, Kuala Lumpur, Does race protect an oriental population from developing Malaysia; A. Kamarulzaman* and C. Sim, University of lipodystrophy in HIV-infected individuals on HAART? J Infect Malaya, Kuala Lumpur, Malaysia; R. Ditangco* Capistrano, Research Institute for Tropical Medicine, 15 Paton NI, Earnest A, Ng YM, Karim F, Aboulhab J.
Manila, Philippine; Y. M. A. Chen*, W. W. Wong and Y.
Lipodystrophy in a cohort of human immunodeficiency virus- R. Chang, Taipei Veterans General Hospital and AIDS infected Asian patients: prevalence, associated factors, and Prevention and Research Centre, National Yang-Ming psychological impact. Clin Infect Dis 2002; 35: 1244–1249.
University, Taipei, Taiwan; P. L. Lim*, C. C. Lee and S. M.
16 Laurent C, Kouanfack C, Koulla-Shiro S et al. Effectiveness and Thitsar, Tan Tock Seng Hospital, Singapore; P. Phanuphak* safety of a generic fixed-dose combination of nevirapine, and M. Khongphattanayothing, HIV-NAT/The Thai Red stavudine, and lamivudine in HIV-1-infected adults in Cameroon: Cross AIDS Research Centre, Bangkok, Thailand; A.
open-label multicentre trial. Lancet 2004; 364: 29–34.
Vibhagool*, S. Kiertiburanakul and W. Kiatatchasai, 17 Zhou J, Kumarasamy N. Predicting short-term disease Ramathibodi Hospital, Bangkok, Thailand; T. Sirianthana*, progression among HIV-infected patients in Asia and the Research Institute for Health Sciences, Chiangmai, Thai- Pacific region: preliminary results from the TREAT Asia HIV land; J. Chuah*, Gold Coast Sexual Health Clinic, Miami, Observational Database. HIV Med 2005; 6: 1–8.
Queensland, Australia; K. Frost* and S. Wong, AmericanFoundation for AIDS Research, New York, NY, USA; D. A.
Appendix: the TREAT Asia HIV Observational Cooper*, M. G. Law*, K. Petoumenos and J. Zhou*, National Centre in HIV Epidemiology and Clinical Research, TheUniversity of New South Wales, Sydney, Australia.
C. V. Mean* and V. Saphonn*, National Center for HIV/ *Steering Committee member; current Steering Com- AIDS, Dermatology & STDs, Phnom Penh, Cambodia; F.
r 2007 British HIV Association HIV Medicine (2007) 8, 8–16
OFFICIAL PROCEEDINGS THIRTY-NINTH ANNUAL PACIFIC NORTHWEST ANIMAL NUTRITION CONFERENCE ALLTECH, INC. PRE-CONFERENCE OCTOBER 5-7, 2004 SEATTLE MARRIOT SEATTLE, WASHINGTON Effect of Prepartum Dietary Cation-Anion Difference on Periparturient Feed Intake and Milk Yield M. A. DeGroot* and P. D. French Oregon State University, Corvallis The objectives of the c