Exhibit 10.1

[IDENIX LETTERHEAD]

November 23, 2010

CONFIDENTIAL

Paul Fanning

17 Stable Way

Medway, MA 02053

Dear Paul:

This restatement to your Employment Letter of February 24, 2004, is made this 23rd day of November, 2010 between you and Idenix Pharmaceuticals, Inc., a corporation incorporated under the laws of the State of Delaware (together with its successors and assigns, the “Company”).

(A) If Idenix terminates your employment other than for Cause (as defined in Appendix A hereto) or you terminate your employment for Good Reason (as defined in Appendix A hereto) you will be eligible to receive the following Severance Compensation.

(i) Lump sum payment equivalent to the sum of (A) one year of Base Salary plus (B) the greater of: (i) target bonus for the year in which your termination of employment occurs; or (ii) the bonus you earned for the year preceding the year in which the termination of your employment occurs, such sum to be reduced by any and all applicable taxes and withholdings;

(ii) Immediate vesting and exercisability of all outstanding equity awards, subject to the terms of such awards; and

(iii) Provided you timely elect and remain eligible for benefits continuation pursuant to the federal “COBRA” laws, continued payment by Idenix of COBRA premiums for you (and your covered dependents) under the group health and dental insurance coverage at the active employee rates for a period of up to 12 months subsequent to the date of your termination. Any such payments and related coverage shall be discontinued in the event that you cease to be eligible for or to elect such COBRA coverage during such 12 month period or if such payments are determined by the Company to be reasonably likely to result in any material tax liability to you or the Company. You will also be eligible for continued premium payment by Idenix if you elect to continue the Idenix provided employee group life insurance coverage for a period of up to 12 months; provided that such continued coverage is permitted under the terms of the life insurance plan. If any such benefit cannot be provided for any reason then the Company will not be obligated to pay you a cash equivalent in lieu of such benefit.

(B) You shall not be eligible to receive the payments, benefits and entitlements provided in subsection (A) of this Section 7 unless you timely execute and allow to become effective within 60 days following your termination (such 60th day, the “Payment Date”), a severance and release of claims agreement (the “Severance Agreement”) substantially similar to the form attached hereto as Appendix C. The Severance Compensation shall begin on the Payment Date and shall be subject to the terms and conditions set forth on Appendix B.

(A) You agree that while you are employed by the Company and for a period of 12 months after the termination or cessation of such employment in the event Idenix terminates your employment for reasons other than cause or you terminate your employment for Good Reason, you will not directly or indirectly:

(i) in the geographic area where the Company does business, has done business, or plans to do business at the time of the termination or cessation of

your employment, engage or assist others in engaging in any business or enterprise (whether as an owner, partner, officer, director, employee, consultant, investor, lender or otherwise) that is competitive with the Company’s business. For purposes of this offer, the term “Competitive Business” shall mean a commercial, for profit entity that discovers, develops and commercializes therapeutics for the treatment of HBV, HCV and HIV; provided that the passive ownership of not more than 1% of the outstanding stock of a publicly-held company shall not, by itself, violate this provision; or

(ii) either alone or in association with others, solicit, divert or take away, or attempt to solicit, divert or take away, the business or patronage of any of the clients, customers, accounts or business partners or prospective clients, customers, accounts or business partners of the Company that were contacted, solicited, or served by the Company while you were employed by the Company; or

(iii) either alone or in association with others solicit, induce or attempt to induce, any employee or independent contractor of the Company to terminate his or her employment or other engagement with the Company, provided, that this provision shall not apply to the solicitation of any individual whose employment or other engagement with the Company has been terminated for a period of six (6) months or longer; and

(B) You agree that during the non-competition and non-solicitation period, you will give notice to the Board of each new business activity you plan to undertake, at least (10) business days prior to beginning any such activity. You further acknowledge and agree that the restrictions contained in this offer letter are necessary for the protection of the business and goodwill of the Company and are considered by you to be reasonable for such purpose. You agree that any breach or threatened breach of this provision will cause the Company substantial and irrevocable damage that is difficult to measure. Therefore, in the event of any such breach or threatened breach, you agree that the Company, in addition to such other remedies that may be available, shall have the right to seek specific performance and injunctive relief without posting a bond. You further waive the adequacy of a remedy at law as a defense to such relief.

If this offer letter correctly sets forth the terms under which you will continue to be employed by the Company, please sign the enclosed duplicate of this letter in the space provided below and return it to me.

Very truly yours,

/s/ Ronald C. Renaud, Jr.

Ronald C. Renaud

President and Chief Executive Officer

Idenix Pharmaceuticals, Inc.

The foregoing correctly sets forth the terms of my at-will employment with Idenix, Inc. I am not relying on any representations other than those set forth above.

ACCEPTED as of this 23rd day of November, 2010

Appendix A

“Change in Control” shall mean:

(i) any “person,” as such term is used in Sections 3(a)(9) and 13(d) of the Securities Exchange Act of 1934, becomes a “beneficial owner,” as such term is used in Rule 13d-3 promulgated under that act, of fifty percent (50%) or more of the Voting Stock of the Company;

(ii) the Company adopts any plan of liquidation providing for the distribution of all or substantially all of its assets;

(iii) all or substantially all of the assets or business of the Company is disposed of pursuant to a merger, consolidation or other transaction (unless the shareholders of the Company immediately prior to such merger, consolidation or other transaction beneficially own, directly or indirectly, at least fifty percent (50%) of the Voting Stock or other ownership interests of the entity or entities, if any, that succeed to the business of the Company); or

(iv) the Company combines with another company and is the surviving corporation but, immediately after the combination, the shareholders of the Company immediately prior to the combination hold, directly or indirectly, fifty percent (50%) or less of the Voting Stock of the combined company (there being excluded from the number of shares held by such shareholders, but not from the Voting Stock of the combined company, any shares received by affiliates of such other company in exchange for stock of such other company).

For purposes of this definition of “Change in Control” the “Company” shall include any entity that succeeds to all or substantially all of the business of the Company and “Voting Stock” shall mean securities of any class or classes having general voting power under ordinary circumstances, in the absence of contingencies, to elect the directors of a corporation.

“Good Reason to terminate your employment with Idenix shall be deemed to exist if, there is: (i) any adverse change in your title or a material diminution in your authority or responsibilities; (ii) a reduction in your Base Salary, the Target Bonus or target equity amount; or (iii) the primary place of your employment is relocated by Idenix to a location more than 40 miles from Cambridge, Massachusetts.

“Termination for Cause” shall be the result of a good faith finding by the Company that you have engaged in: (i) willful fraud or willful material dishonesty in connection with your employment by the Company; (ii) intentional failure by you to substantially perform your duties hereunder or gross neglect in the performance of such duties; (iii) your gross misconduct that is materially detrimental to the Company’s reputation, goodwill or business operations; (iv) your breach of any of the covenants in this offer or attachments hereto; or (v) your conviction of, or plea of nolo contendere to, a charge of commission of a felony; provided that prior to any Termination for Cause you are given written notice with specificity of any such reasons and a reasonable opportunity to cure if such a cure is reasonably possible.

Appendix B

Payments Subject to Section 409A

Subject to the provisions in this Appendix B, any Severance Compensation or benefits under this offer of employment shall be made only upon the date of your “separation from service” (determined as set forth below) which occurs on or after the date of termination of your employment. The following rules shall apply with respect to distribution of the Severance Compensation, if any, to be provided to you under this letter:

(i) It is intended that each installment of the Severance Compensation shall be treated as a separate “payment” for purposes of Section 409A of the Internal Revenue Code of 1986, as amended, and the guidance issued thereunder (“Section 409A”). Neither the Company nor you shall have the right to accelerate or defer the delivery of any such payments or benefits except to the extent specifically permitted or required by Section 409A.

(ii) If, as of the date of your “separation from service” from the Company, you are not a “specified employee” (within the meaning of Section 409A), then each installment of the Severance Compensation shall be made on the dates and terms set forth in this letter.

(iii) If, as of the date of your “separation from service” from the Company, you are a “specified employee” (within the meaning of Section 409A), then:

(a) each installment of the Severance Compensation due under this letter that, in accordance with the dates and terms set forth herein, will in all circumstances, regardless of when the separation from service occurs, be paid within the short-term deferral period (as defined under Section 409A) shall be treated as a short-term deferral within the meaning of Treasury Regulation § 1.409A 1(b)(4) to the maximum extent permissible under Section 409A, and shall be made on the dates and terms set forth in this letter; and

(b) each installment of the Severance Compensation due under this letter that is not described in this Appendix, (iii)(a) above and that would, absent this subsection, be paid within the six-month period following your “separation from service” from the Company shall not be paid until the date that is six months and one day after such separation from service (or, if earlier, your death), with any such installments that are required to be delayed being accumulated during the six-month period and paid in a lump sum on the date that is six months and one day following your separation from service and any subsequent installments, if any, being paid in accordance with the dates and terms set forth herein; provided, however, that the preceding provisions of this sentence shall not apply to any installment of Severance Compensation if and to the maximum extent that that such installment is deemed to be paid under a separation pay plan

that does not provide for a deferral of compensation by reason of the application of Treasury Regulation § 1.409A-1(b)(9)(iii) (relating to separation pay upon an involuntary separation from service). Any installments that qualify for the exception under Treasury Regulation § 1.409A-1(b)(9)(iii) must be paid no later than the last day of your second taxable year following the taxable year in which the separation from service occurs.

(iv) The determination of whether and when your separation from service from the Company has occurred shall be made and in a manner consistent with, and based on the presumptions set forth in, Treasury Regulation § 1.409A-1(h). Solely for purposes of this Appendix B, (iv), “Company” shall include all persons with whom the Company would be considered a single employer as determined under Treasury Regulation Section 1.409A-1(h)(3).

(v) All reimbursements and in-kind benefits provided under this letter shall be made or provided in accordance with the requirements of Section 409A to the extent that such reimbursements or in-kind benefits are subject to Section 409A, including, where applicable, the requirements that (i) any reimbursement is for expenses incurred during your lifetime (or during a shorter period of time specified in this letter), (ii) the amount of expenses eligible for reimbursement during a calendar year may not affect the expenses eligible for reimbursement in any other calendar year, (iii) the reimbursement of an eligible expense will be made on or before the last day of the calendar year following the year in which the expense is incurred and (iv) the right to reimbursement is not subject to set off or liquidation or exchange for any other benefit.

(vi) Notwithstanding anything herein to the contrary, the Company shall have no liability to you or to any other person if the payments and benefits provided hereunder that are intended to be exempt from or compliant with Section 409A are not so exempt or compliant.

Appendix C

Form of Severance and General Release Agreement

[Insert Date]

[Insert Employee Name]

[Insert Employee Address]

Dear [Insert Employee Name]:

As we have discussed, your employment with Idenix, Inc. (the “Company”) will end on [Insert Termination Date]. The Company will provide you with the severance benefits described in paragraph 2 below if you sign and return this letter agreement (the “Agreement”) to me on or before [Insert Return Date] and it becomes binding between you and the Company. By timely signing and returning this Agreement and not revoking your acceptance, you will be entering into a binding agreement with the Company and will be agreeing to the terms and conditions set forth in the numbered paragraphs below, including the release of claims set forth in paragraph 3. Therefore, you are advised to consult with an attorney before signing this Agreement and you have been given at least twenty-one (21) days to do so. If you sign this Agreement, you may change your mind and revoke your agreement during the seven (7) day period after you have signed it by notifying me in writing. If you do not so revoke, this Agreement will become a binding agreement between you and the Company upon the expiration of the seven (7) day period.

If you choose not to sign and return this Agreement in a timely manner as set forth above, or if you timely revoke your acceptance in writing, you shall not receive any of the severance payments or benefits under your restated employment letter dated as of                  ,      (your “Employment Letter”) from the Company. Whether or not this Agreement becomes effective, you will receive payment on your Termination Date, as defined herein, for (i) your final wages and (ii) any unused vacation time accrued through the Termination Date. You may also, if eligible, elect to continue receiving group medical insurance pursuant to the federal “COBRA” law, 29 U.S.C. § 1161 et seq. Please consult the COBRA materials to be provided by the Company under separate cover for details regarding these benefits. Except as provided for herein, all other benefits and all unvested stock rights will be cancelled on the Termination Date.

The following numbered paragraphs set forth the terms and conditions that will apply if you timely sign and return this Agreement and do not revoke it in writing within the seven (7) day period.

Notwithstanding any provision of this Agreement to the contrary, by executing this Agreement, you are not releasing (i) any claims that cannot be waived by law, (ii) your right of indemnification as provided by, and in accordance with the terms of, the Company’s by-laws or a Company insurance policy providing such coverage, as any of such may be amended from time to time, or (iii) any claims relating to your rights as an equity holder of the Company.

If you have any questions about the matters covered in this Agreement, please call                     .

I hereby agree to the terms and conditions set forth above. I have been given at least twenty-one (21) days to consider this Agreement and I have chosen to execute this on the date below. I intend that this Agreement will become a binding agreement between me and the Company if I do not revoke my acceptance in seven (7) days.