This publication is intended to serve as a reference tool for countries with limited resources as they develop or revise national guidelines for the use of ART in adults and postpubertal adolescents (see Annex 9 for pubertal Tanner staging; prepubertal adolescents should follow the WHO paediatric guidelines). The material presented takes updated evidence into account including new ART treatment options and draws on the experience of established ART scale-up programmes. The simplified approach with evidence-based standards continues to be the basis of WHO recommendations for the initiation and monitoring of ART. The guidelines are primarily intended for use by national and regional HIV programme managers managers of nongovernmental organizations delivering HIV care services and other policy-makers who are involved in the scaling up of comprehensive HIV care and ART in resource-limited countries. The comprehensive up-to-date technical and clinical information on the use of ART however also makes these guidelines useful for clinicians in resource-limited settings. The recommendations contained in these guidelines are made on the basis of different levels of evidence from randomized clinical trials high-quality scientific studies observational cohort data and where insufficient evidence is available expert opinion. The strengths of the recommendations in Table 1 are intended to indicate the degrees to which the recommendations should be considered by regional and country programmes. Cost-effectiveness is not explicitly considered as part of the recommendations although the realities of human resources health system infrastructures and socioeconomic issues should be taken into account when the recommendations are being adapted to regional and country programmes. (excerpt)

Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach. 2006 revision.

ContextTenofovir disoproxil fumarate (DF) is a once-daily nucleotide analogue
reverse transcriptase inhibitor.ObjectiveTo evaluate the efficacy and safety of tenofovir DF compared with stavudine
in antiretroviral-naive patients.Design, Setting, and ParticipantsA prospective, randomized, double-blind study conducted at 81 centers
in the United States, South America, and Europe from June 9, 2000, to January
30, 2004. A total of 753 patients infected with HIV who were antiretroviral
naive were screened and 602 patients entered the study.InterventionPatients were randomized to receive either tenofovir DF (n = 299) or
stavudine (n = 303), with placebo, in combination with lamivudine and efavirenz.Main Outcome MeasureProportion of patients with HIV RNA levels of less than 400 copies/mL
at week 48.ResultsIn the primary intent-to-treat analysis in which patients with missing
data or who added or switched antiretroviral medications before week 48 were
considered as failures, the proportion of patients with HIV RNA of less than
400 copies/mL at week 48 was 239 (80%) of 299 in patients receiving tenofovir
DF and 253 (84%) of 301 in patients receiving stavudine (95% confidence interval,
−10.4% to 1.5%), exceeding the predefined −10% limit for equivalence.
However, equivalence was demonstrated in the secondary analyses (HIV RNA <50
copies/mL) at week 48 and through 144 weeks. Virologic failure was associated
most frequently with efavirenz and lamivudine resistance. Through 144 weeks,
the K65R mutation emerged in 8 and 2 patients in the tenofovir DF and stavudine
groups, respectively (P = .06). A more favorable
mean change from baseline in fasting lipid profile was noted in the tenofovir
DF group at week 144: for triglyceride levels (+1 mg/dL for tenofovir DF [n
= 170] vs +134 mg/dL for stavudine [n = 162], P<.001),
total cholesterol (+30 mg/dL [n = 170] vs +58 mg/dL [n = 162], P<.001), direct low-density lipoprotein cholesterol (+14 mg/dL [n
= 169] vs +26 mg/dL [n = 161], P<.001), and high-density
lipoprotein cholesterol (+9 mg/dL [n = 168] vs +6 mg/dL [n = 154], P = .003). Investigator-reported lipodystrophy was less common in the
tenofovir DF group compared with the stavudine group (9 [3%] of 299 vs 58
[19%] of 301, P<.001). The number of bone fractures
and the renal safety profile were similar between the 2 groups.ConclusionsThrough 144 weeks, the combination of tenofovir DF, lamivudine, and
efavirenz was highly effective and comparable with stavudine, lamivudine,
and efavirenz in antiretroviral-naive patients. However, tenofovir DF appeared
to be associated with better lipid profiles and less lipodystrophy.

https://jamanetwork.com/journals/jama/articlepdf/199084/JOC40511.pdf

Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial.

Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies

BACKGROUND
Combination antiretroviral therapy has led to significant increases in survival and quality of life, but at a population-level the effect on life expectancy is not well understood. Our objective was to compare changes in mortality and life expectancy among HIV-positive individuals on combination antiretroviral therapy.


METHODS
The Antiretroviral Therapy Cohort Collaboration is a multinational collaboration of HIV cohort studies in Europe and North America. Patients were included in this analysis if they were aged 16 years or over and antiretroviral-naive when initiating combination therapy. We constructed abridged life tables to estimate life expectancies for individuals on combination antiretroviral therapy in 1996-99, 2000-02, and 2003-05, and stratified by sex, baseline CD4 cell count, and history of injecting drug use. The average number of years remaining to be lived by those treated with combination antiretroviral therapy at 20 and 35 years of age was estimated. Potential years of life lost from 20 to 64 years of age and crude mortality rates were also calculated.


FINDINGS
18 587, 13 914, and 10 854 eligible patients initiated combination antiretroviral therapy in 1996-99, 2000-02, and 2003-05, respectively. 2056 (4.7%) deaths were observed during the study period, with crude mortality rates decreasing from 16.3 deaths per 1000 person-years in 1996-99 to 10.0 deaths per 1000 person-years in 2003-05. Potential years of life lost per 1000 person-years also decreased over the same time, from 366 to 189 years. Life expectancy at age 20 years increased from 36.1 (SE 0.6) years to 49.4 (0.5) years. Women had higher life expectancies than did men. Patients with presumed transmission via injecting drug use had lower life expectancies than did those from other transmission groups (32.6 [1.1] years vs 44.7 [0.3] years in 2003-05). Life expectancy was lower in patients with lower baseline CD4 cell counts than in those with higher baseline counts (32.4 [1.1] years for CD4 cell counts below 100 cells per muL vs 50.4 [0.4] years for counts of 200 cells per muL or more).


INTERPRETATION
Life expectancy in HIV-infected patients treated with combination antiretroviral therapy increased between 1996 and 2005, although there is considerable variability between subgroups of patients. The average number of years remaining to be lived at age 20 years was about two-thirds of that in the general population in these countries.

Antiretroviral therapy cohort collaboration : life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies

The 2008 BHIVA Guidelines have been updated to incorporate all the new relevant information (including presentations at the 15th Conference on Retroviruses and Opportunistic Infections 2008) since the last iteration. The guidelines follow the methodology outlined below and all the peer-reviewed publications and important, potentially treatment-changing abstracts from the last 2 years have been reviewed.


The translation of data into clinical practice is often difficult even with the best possible evidence (i.e. two randomized controlled trials) because of trial design, inclusion criteria and precise surrogate marker endpoints (see Appendix). The recommendations based upon expert opinion have the least good evidence but perhaps provide an important reason for writing the guidelines to produce a consensual opinion about current practice. It must, however, be appreciated that such opinion is often wrong and should not stifle research to challenge it.


Similarly, although the Writing Group seeks to provide guidelines to optimize treatment, such care needs to be individualized and we have not constructed a document that we would wish to see used as a ‘standard’ for litigation.

/pdf/british-hiv-association-guidelines-for-the-treatment-of-hiv-10vdb5k2uo.pdf

British HIV Association guidelines for the treatment of HIV-1-infected adults with antiretroviral therapy 2008

Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study

G Reboredo

Papers

Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study