• Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Oral Mucosa) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
• Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Lymphocytes) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
• Change From Baseline in Lactate Concentration [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
• Percentage of Days for Which Participants Were Compliant With Study Drug [ Time Frame: 72 weeks ] [ Designated as safety issue: No ]
• Percentage of Participants Who Maintain Confirmed HIV-1 RNA < 50 Copies/mL [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
• Percentage of Participants With HIV-1 RNA > 50 and < 400 Copies/mL [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
• Percentage of Participants With Virologic Failure [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
• Change From Baseline in Cluster Determinant 4 (CD4) Cell Count [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
• Change From Baseline in Fasting Serum Triglycerides [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
• Change From Baseline in Fasting Total Cholesterol [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
• Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
• Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
• Change From Baseline in Hemoglobin [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
• Change From Baseline in Hematocrit [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
• Change From Baseline in Waist Circumference/Hip Circumference Ratio [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
• Percentage of Participants With Any Adverse Event [ Time Frame: 72 weeks ] [ Designated as safety issue: Yes ]
• Percentage of Participants Who Discontinue the Study Prematurely (Before Week 48) Due to Adverse Events. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

• Change in the mitochondrial DNA/nuclear DNA ratio in the different visits compared with baseline.
• Change in lactate concentration in the different visits compared with baseline.
• Proportion of patients who maintain confirmed VIH-1 RNA levels of < 50 copies/mL.
• Proportion of patients with HIV-1 RNA levels between >50 and <400 copies/mL.
• Proportion of patients with virologic failure defines as confirmed with two consecutive HIV RNA >400 copies/mL.
• Time to loss of virological response, defined as the time elapsed from the patient’s first dose of study drug to confirmed HIV-1 RNA levels of > 50 and < 400 copies/mL, death caused by the disease, medication discontinuation, or addition of a new antire
• Time to definite virological failure, defined as the time elapsed from the patient’s first dose of study drug to confirmed HIV-1 RNA levels of > 400 copies/mL.
• Change in CD4+ cell counts in the different study visits compared with baseline.
• Change in serum triglycerides, total cholesterol, LDL, and HDL fractions in the different study visits compared with baseline.
• Change in hemoglobin and hematocrit concentrations in the different visits compared with baseline.
• Proportion of patients with different specific mutations after virological failure.
• Proportion of patients who show treatment adherence (assessed according to SMQA questionnaire, see Appendix 10).
• The following endpoints will be considered to asses tolerability after coding the adverse events:
•  Proportion of patients with any adverse event.
•  Proportion of patients for each adverse event.
•  Distribution of the intensity if each adverse event (the greatest intensity for each adverse event within a patient will be considered).
•  Distribution of the relationship between the adverse effect and the study drug (the strongest relation with the study drug for each adverse event within each patient will be considered).
•  Proportion of patients who discontinue the study prematurely (before week 48) due to adverse events.

This study evaluated changes in body fat distribution in human immunodeficiency virus type 1 (HIV-1) infected participants who either switched from a zidovudine- (AZT) plus lamivudine- (3TC) containing antiretroviral regimen to a regimen containing Truvada® (a fixed-dose combination tablet of emtricitabine [FTC, 200 mg] and tenofovir disoproxil fumarate [TDF, 300 mg]) or who remained on an AZT plus 3TC-containing regimen.

Standard care for the treatment of HIV infection involves the use of a combination of three antiretroviral drugs. The initial recommended regimen in antiretroviral-naive patients according to therapeutic guidelines of the US Department of Health and Human Resources (DHHS) includes two nucleoside reverse transcriptase inhibitors (NRTIs) and a third drug from another class (protease inhibitor [PI] or non-nucleoside reverse transcriptase inhibitor [NNRTI]).

The use of nucleoside analogues, especially stavudine and AZT, is associated with untoward side effects, including lipodystrophy hepatic steatosis/lactic acidosis syndrome, peripheral neuropathy, and anemia. However, Truvada has a low potential for both mitochondrial toxicity and fat distribution disturbances.

As described in the Consensus Document of the Spanish Group for the Study of AIDS (GESIDA), and the AIDS National Plan from the Spanish Ministry of Health "Recommendations on metabolic alterations and body fat distribution", studies should focus on the evaluation of body fat disturbances after antiretroviral drug substitutions, based on the basic assumption of virologic control of the patient and equivalence in potency of the new drug regarding virological control. In addition, studies based on selective substitution of antiretroviral drugs in HIV-1 infected patients under virological control, are recommended in the EMEA in the "Guideline on the clinical development of medicinal products for the treatment of HIV infection".

In this study, stable, virologically controlled, HIV-1 infected participants receiving antiretroviral regimens containing AZT and 3TC were randomized to switch to Truvada or to stay on their AZT- plus 3TC-containing regimen. Participants in both groups continued the third drug of their antiretroviral regimen (either an NNRTI or PI). Changes in limb fat in the two groups were assessed using dual-energy x-ray absorptiometry (DEXA).

• Drug: Truvada
• Drug: AZT/3TC

• Experimental: Truvada + NNRTI or PI.
• Active Comparator: AZT/3TC + NNRTI or PI.

Inclusion Criteria:

• HIV-1 infection documented by confirmed positive HIV-1 antibody test and/or positive polymerase chain reaction for HIV-1 ribonucleic acid (RNA).
• Adult patients (over 18 years of age).
• Current highly active antiretroviral therapy (HAART) regimen containing AZT + 3TC at usual doses for at least 6 months.
• Viral load < 50 copies/mL on the last two consecutive determinations, under AZT + 3TC containing HAART regimen.
• For women of childbearing potential, negative urine pregnancy test at screening visit.
• Agreement to take part in the study and sign the informed consent.
• Patients on lipid lowering treatment were allowed to participate in the study only if the lipid-lowering treatment (either statins or fibrates) was stable for at least 8 weeks prior to screening and it was not expected to change during the first 3 months of the study.

Exclusion Criteria:

• Patients on current TDF or FTC therapy.
• Patients with previous history of virological failure on an FTC or TDF-containing regimen.
• Patients receiving a non-registered antiretroviral drug.
• Patients receiving a triple-nucleoside antiretroviral combination.
• Hypersensitivity to one of the components of the dosage forms of TDF or FTC, or previous history of intolerance to one of those drugs.
• Known history of drug abuse or chronic alcohol consumption
• Women who were pregnant or breast feeding, or female of childbearing potential who did not use an adequate method of contraception according to the investigator's judgment.
• Active opportunistic infection or documented infection within the previous 4 weeks.
• Documented active malignant disease (excluding Kaposi sarcoma limited to the skin).
• Renal disease with creatinine clearance < 50 mL/min.
• Concomitant use of nephrotoxic or immuno-suppressive drugs which could not be stopped without affecting the safety of the patient.
• Receiving on-going therapy with systemic corticosteroids, Interleukin-2 or chemotherapy.
• Patients who were not to be included in the study according to the investigator's criterion.