Two stud­ies con­firm kid­ney side-effects are rare when tak­ing PrEP. One of the stud­ies, led by the World Health Orga­ni­za­tion (WHO), also indi­cates that peo­ple under the age of 30 tak­ing PrEP may need less fre­quent kid­ney screen­ing. A sep­a­rate group of researchers say that peo­ple who expe­ri­ence kid­ney side-effects might ben­e­fit from switch­ing from tak­ing dai­ly pills to event-based dos­ing instead of stop­ping the med­i­cine alto­geth­er.

Both stud­ies looked specif­i­cal­ly at teno­fovir diso­prox­il fumarate (TDF)-based PrEP, which affects kid­ney func­tion in a small num­ber of peo­ple, espe­cial­ly in those above the age of 50 and those with base­line kid­ney val­ues already below nor­mal. While declines in kid­ney func­tion are small and reversible after stop­ping PrEP, con­cerns over them can be a bar­ri­er to tak­ing it. Anoth­er bar­ri­er is hav­ing to make fre­quent clin­ic vis­its to mon­i­tor kid­ney func­tion; cur­rent­ly many guide­lines rec­om­mend mea­sur­ing blood cre­a­ti­nine every six months.

Gay and bisex­u­al men can use event-based dos­ing (also known as on-demand PrEP) instead of a dai­ly pill. Event-based dos­ing requires plan­ning ahead because it involves tak­ing a dou­ble dose (two pills) between 2 and 24 hours before sex, a sin­gle dose (one pill) 24 hours lat­er, and anoth­er sin­gle dose 24 hours after that. Event-based dos­ing is not rec­om­mend­ed for peo­ple at risk of acquir­ing HIV through vagi­nal sex because there aren’t enough data on how this approach affects lev­els of drugs in vagi­nal tis­sues.

In the study led by WHO, researchers con­duct­ed two sep­a­rate meta-analy­ses to iden­ti­fy pop­u­la­tions of peo­ple who might require less fre­quent mon­i­tor­ing of kid­ney func­tion. The first meta-analy­sis used sum­ma­ry data from eleven ran­domised clin­i­cal tri­als to eval­u­ate the rel­a­tive risks of peo­ple on PrEP expe­ri­enc­ing grade 1 and high­er adverse kid­ney events (blood cre­a­ti­nine lev­els of 1.1 to 1.3 times the typ­i­cal val­ues) and grade 2 and high­er adverse kid­ney events (blood cre­a­ti­nine lev­els of 1.3 to 1.8 times the typ­i­cal val­ues).

This analy­sis involved 13,523 study par­tic­i­pants across 13 coun­tries with diverse gen­ders and sex­u­al ori­en­ta­tions, although the per­cent­ages with­in each group were not report­ed. The analy­sis found peo­ple tak­ing PrEP had about 1.5 times high­er risk of devel­op­ing grade 1 or high­er kid­ney events (272 out of 6764 peo­ple tak­ing PrEP com­pared to 183 out of 6769 peo­ple in the con­trol group). The odds ratio of peo­ple on PrEP expe­ri­enc­ing grade 2 or high­er kid­ney events was 1.75, but it was not sta­tis­ti­cal­ly sig­nif­i­cant (13 out of 6764 peo­ple tak­ing PrEP com­pared to six of 6782 peo­ple in the con­trol group).

The sec­ond meta-analy­sis used indi­vid­ual par­tic­i­pant data from 19 PrEP pro­grammes and stud­ies (most of which had not pre­vi­ous­ly pub­lished their data) that respond­ed to a request for data issued by WHO. The researchers defined clin­i­cal­ly sig­nif­i­cant declines in kid­ney func­tion asso­ci­at­ed with PrEP use as esti­mat­ed cre­a­ti­nine clear­ance lev­els that decreased to below 60 mL/min, which is con­sid­ered abnor­mal (greater than 90 mL/min is nor­mal, and between 60 and 90 mL/min is mod­er­ate kid­ney func­tion).

This analy­sis looked at data from 18,676 peo­ple from 15 coun­tries, includ­ing about 40% from high income coun­tries and about 60% from low- and mid­dle-income coun­tries. The par­tic­i­pants were most­ly men (76%), but 22% of the par­tic­i­pants were cis­gen­der female and 2% were trans­gen­der female. About half (48%) were under the age of 30 and most (78%) had nor­mal kid­ney func­tion —only 0.4% had abnor­mal esti­mat­ed cre­a­ti­nine clear­ance lev­els dur­ing PrEP screen­ing.

PrEP users who had at least one clin­i­cal fol­low-up (14,368) were includ­ed in the detailed analy­sis, and 349 (2.4%) of them expe­ri­enced clin­i­cal­ly sig­nif­i­cant declines in kid­ney func­tion. Of 263 peo­ple who had fol­low up mea­sure­ments, 217 (83%) returned to mod­er­ate or nor­mal val­ues with­out stop­ping PrEP. Peo­ple old­er than 50 years of age had a six-fold increase in risk of expe­ri­enc­ing clin­i­cal­ly sig­nif­i­cant declines. Peo­ple whose kid­ney func­tions before start­ing PrEP were in the mod­er­ate range had an eight-fold high­er risk of expe­ri­enc­ing clin­i­cal­ly sig­nif­i­cant declines com­pared to those with nor­mal kid­ney func­tion.

This analy­sis showed a slight­ly high­er risk of decline in kid­ney func­tion in cis­gen­der female PrEP users com­pared to cis­gen­der male, but the result was not sta­tis­ti­cal­ly sig­nif­i­cant, per­haps because too few of the projects fol­lowed females. Sim­i­lar­ly, too few trans­gen­der and non­bi­na­ry peo­ple were includ­ed to draw any con­clu­sions about these pop­u­la­tions.

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The Lon­don-based study includ­ed 13,980 peo­ple who received PrEP from nurs­es dur­ing a two-year peri­od from a sin­gle health­care facil­i­ty (56 Dean Street). It eval­u­at­ed 220 peo­ple (1.6%) who need­ed addi­tion­al con­sul­ta­tions with physi­cians because of med­ical issues they expe­ri­enced while tak­ing PrEP. Most of the 220 peo­ple were male (98%) and White (75%). The major­i­ty of this group (52%) expe­ri­enced declines in kid­ney func­tion, mea­sured in one of sev­er­al ways, includ­ing high cre­a­ti­nine lev­els and abnor­mal esti­mat­ed glomeru­lar fil­tra­tion rates.

Both stud­ies con­firmed pre­vi­ous results that kid­ney effects were rare, didn’t progress, and resolved after stop­ping PrEP.”

Declines in kid­ney func­tion prompt­ed more fre­quent mon­i­tor­ing and, if they per­sist­ed, were man­aged in two ways. About half of the peo­ple with mod­er­ate declines in kid­ney func­tion reduced pro­tein intake, includ­ing through dietary changes and stop­ping pro­tein sup­ple­ments (often used by body­builders). Oth­ers with more severe declines in kid­ney func­tion were switched from a dai­ly PrEP dosage to either an event-based dosage or four tablets a week on Tues­day, Thurs­day, Sat­ur­day, Sun­day (called 2Ts 2Ss). How­ev­er, a few had to dis­con­tin­ue tak­ing PrEP after try­ing these low­er-dose approach­es.

The WHO researchers rec­om­mend reduc­ing the bar­ri­er of fre­quent kid­ney mon­i­tor­ing for younger peo­ple. As a result, WHO updat­ed their guide­lines to say that cre­a­ti­nine screen­ing can be option­al for peo­ple tak­ing PrEP who are less than 30 years old and don’t have oth­er co-mor­bidi­ties. For those old­er than 30 years or with co-mor­bidi­ties, WHO rec­om­mends screen­ing once with­in three months of start­ing PrEP. Screen­ing every six to twelve months is only rec­om­mend­ed for peo­ple who have co-mor­bidi­ties, for those old­er than 50 years regard­less of co-mor­bidi­ties, and for any­one with a pre­vi­ous cre­a­ti­nine clear­ance result of less than 90 mL/min.

Both stud­ies con­firmed pre­vi­ous results that kid­ney effects were rare, didn’t progress, and resolved after stop­ping PrEP. Fur­ther­more, the sec­ond analy­sis showed that the vast major­i­ty of people’s kid­ney func­tion val­ues returned to nor­mal with­out hav­ing to stop PrEP.

Stop­ping PrEP in the face of ongo­ing kid­ney-relat­ed side-effects may not be the only option. If avail­able, both teno­fovir alafe­namide-based PrEP or injectable cabote­gravir have few­er kid­ney-relat­ed side-effects. The Lon­don researchers say that mov­ing peo­ple to an event-based approach may be a valid way to keep peo­ple on TDF-based PrEP while min­imis­ing adverse kid­ney effects. Fur­ther­more, they said, this approach can be tried if oth­er types of adverse side-effects are expe­ri­enced while tak­ing PrEP.

(Bron: NAM Aidsmap 01/04/2022)

Last updated 11/04/2022