HIV Cure?

Wellness Update - - Hiv -

Ateam of re­searchers from Johns Hop­kins Chil­dren’s Cen­ter, the Univer­sity of Mis­sis­sippi Med­i­cal Cen­ter and the Univer­sity of Mas­sachusetts Med­i­cal School de­scribe the first case of a so-called “func­tional cure” in an HIV-in­fected in­fant. The find­ing, the in­ves­ti­ga­tors say, may help pave the way to elim­i­nat­ing HIV in­fec­tion in chil­dren.

A report on the case is sched­uled for pre­sen­ta­tion at a press con­fer­ence on Sun­day, March 3, at the 20th Con­fer­ence on Retro­viruses and Op­por­tunis­tic In­fec­tions (CROI) in At­lanta. Johns Hop­kins Chil­dren’s Cen­ter vi­rol­o­gist Deb­o­rah Per­saud, M.D., lead au­thor on the report, and Univer­sity of Mas­sachusetts Med­i­cal School im­mu­nol­o­gist Kather­ine Luzuriaga, M.D., headed a team of lab­o­ra­tory in­ves­ti­ga­tors. Pe­di­atric HIV spe­cial­ist Han­nah Gay, M.D., as­so­ciate pro­fes­sor of pe­di­atrics at the Univer­sity of Mis­sis­sippi Med­i­cal Cen­ter pro­vided treat­ment to the baby. The in­fant de­scribed in the report un­der­went re­mis­sion of HIV in­fec­tion af­ter re­ceiv­ing an­tiretro­vi­ral ther­apy (ART) within 30 hours of birth. The in­ves­ti­ga­tors say the prompt ad­min­is­tra­tion of antiviral treat­ment likely led to this in­fant’s cure by halt­ing the for­ma­tion of hard-to-treat vi­ral reser­voirs — dor­mant cells re­spon­si­ble for reignit­ing the in­fec­tion in most HIV pa­tients within weeks of stop­ping ther­apy.

“Prompt antiviral ther­apy in new­borns that be­gins within days of ex­po­sure may help in­fants clear the virus and achieve long-term re­mis­sion with­out life­long treat­ment by prevent­ing such vi­ral hide­outs from form­ing in the first place,” Per­saud says.

The re­searchers say they be­lieve this is pre­cisely what hap­pened in the child de­scribed in the report. That in­fant is now deemed “func­tion­ally cured,” a con­di­tion that oc­curs when a pa­tient achieves and main­tains long-term vi­ral re­mis­sion with­out life­long treat­ment and stan­dard clin­i­cal tests fail to de­tect HIV repli­ca­tion in the blood.

In con­trast to a ster­il­iz­ing cure — a com­plete erad­i­ca­tion of all vi­ral traces from the body — a func­tional cure oc­curs when vi­ral pres­ence is so min­i­mal, it re­mains

un­de­tectable by stan­dard clin­i­cal tests, yet dis­cernible by ul­tra­sen­si­tive meth­ods.

The child de­scribed in the cur­rent report was born to an HIVin­fected mother and re­ceived com­bi­na­tion an­tiretro­vi­ral treat­ment be­gin­ning 30 hours af­ter birth. A se­ries of tests showed pro­gres­sively di­min­ish­ing vi­ral pres­ence in the in­fant’s blood, un­til it reached un­de­tectable lev­els 29 days af­ter birth. The in­fant re­mained on an­tivi­rals un­til 18 months of age, at which point the child was lost to fol­low-up for a while and, the re­searchers say, stopped treat­ment. Ten months af­ter dis­con­tin­u­a­tion of treat­ment, the child un­der­went re­peated stan­dard blood tests, none of which de­tected HIV pres­ence in the blood. Test for HIV-spe­cific an­ti­bod­ies — the stan­dard clin­i­cal in­di­ca­tor of HIV in­fec­tion — also re­mained neg­a­tive through­out.

Cur­rently, high-risk new­borns — those born to moth­ers with poorly con­trolled in­fec­tions or whose moth­ers’ HIV sta­tus is dis­cov­ered around the time of de­liv­ery — re­ceive a com­bi­na­tion of an­tivi­rals at pro­phy­lac­tic doses to pre­vent in­fec­tion for six weeks and start ther­a­peu­tic doses if and once in­fec­tion is di­ag­nosed. But this par­tic­u­lar case, the in­ves­ti­ga­tors say, may change the cur­rent prac­tice be­cause it high­lights the cu­ra­tive po­ten­tial of very early ART.

Spe­cial­ists say nat­u­ral vi­ral sup­pres­sion with­out treat­ment is an ex­ceed­ingly rare phe­nom­e­non ob­served in less than half a per­cent of HIV-in­fected adults, known as “elite con­trollers,” whose im­mune sys­tems are able to rein in vi­ral repli­ca­tion and keep the virus at clin­i­cally un­de­tectable lev­els. HIV ex­perts have long sought a way to help all HIV pa­tients achieve elite­con­troller sta­tus. The new case, the re­searchers say, may be that long-sought game-changer be­cause it sug­gests prompt ART in new­borns can do just that.

The in­ves­ti­ga­tors cau­tion they don’t have enough data to rec­om­mend change right now to the cur­rent prac­tice of treat­ing high-risk in­fants with pro­phy­lac­tic, rather than ther­a­peu­tic, doses but the in­fant’s case pro­vides the ra­tio­nale to start proofof-prin­ci­ple stud­ies in all high-risk new­borns.

“Our next step is to find out if this is a highly un­usual re­sponse to very early an­tiretro­vi­ral ther­apy or some­thing we can ac­tu­ally repli­cate in other high-risk new­borns,” says Per­saud, who is also the sci­en­tific chair of the HIV Cure Com­mit­tee of the In­ter­na­tional Ma­ter­nal, Pe­di­atric Ado­les­cent AIDS Clin­i­cal (IMPAACT) net­work, a con­sor­tium of re­searchers and in­sti­tu­tions that was crit­i­cal in spear­head­ing the ear­li­est clin­i­cal tri­als of mother-to-child trans­mis­sion and early treat­ment of in­fants 15 years ago.

A sin­gle case of ster­il­iz­ing cure has been re­ported so far, the in­ves­ti­ga­tors note. It oc­curred in an HIV­pos­i­tive man treated with a bone mar­row trans­plant for leukemia. The bone mar­row cells came from a donor with a rare ge­netic mu­ta­tion of the white blood cells that ren­ders some peo­ple re­sis­tant to HIV, a ben­e­fit that trans­ferred to the re­cip­i­ent. Such a com­plex treat­ment ap­proach, how­ever, HIV ex­perts agree, is nei­ther fea­si­ble nor prac­ti­cal for the 33 mil­lion peo­ple world­wide in­fected with HIV.

“Com­plete vi­ral erad­i­ca­tion on a large scale is our long-term goal but, for now, re­mains out of reach, and our best chance may come from ag­gres­sive, timely and pre­cisely tar­geted use of antiviral ther­a­pies in high-risk new­borns as a way to achieve func­tional cure,” Luzuriaga says.

De­spite the prom­ise this ap­proach holds for in­fected new­borns, the re­searchers say prevent­ing moth­erto-child trans­mis­sion re­mains the pri­mary goal.

“Preven­tion really is the best cure, and we al­ready have proven strate­gies that can pre­vent 98 per­cent of new­born in­fec­tions by iden­ti­fy­ing and treat­ing HIV-pos­i­tive preg­nant women,” says Gay, the HIV ex­pert who treated the in­fant.

The re­search was funded by the Na­tional In­sti­tutes of Health and by the Amer­i­can Foun­da­tion for AIDS Re­search (amfAR). -This in­for­ma­tion pro­vided courtesy of the Univer­sity of Mis­sis­sippi Med­i­cal Cen­ter

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