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Little Gain From Drug Breaks After Treating Primary Infection
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Mark Mascolini
XVI Intl AIDS Conference, Toronto
August 14, 2006
PRIMSTOP, a nonrandomized trial of structured drug breaks after treatment for primary HIV infection, found that "virtually no patient" who tried this strategy kept tight control of HIV replication without antiretroviral therapy (ART). Six people had to restart ART after a median of 1 year without drugs, and 2 people who didn't resume therapy suffered clinical progression.
A comparison of two German primary infection cohorts suggested, on the other hand, that fast treatment of early infection may make sense for people with a first viral load above 50,000 copies/mL, if they they're willing to take antiretrovirals for 9 months or so [2].
PRIMSTOP enrolled 29 people who started ART during symptomatic acute HIV infection and continued therapy for 34 weeks [3]. At that point, with a viral load under 50 copies/mL, they took three consecutive drug holidays of 2, 4, and 8 weeks interspersed with 12 weeks of therapy.
When they halted treatment at week 84 the PRIMSTOP team tracked them to see how many maintained a sub-50-copy viral load through week 108, which was the study's primary endpoint.
Only 1 of 26 people (4%) who stopped ART at week 84 kept a sub-50 load through week 108, while 3 (11.5%) stayed under 400 copies/mL the whole time and 5 (19%) stayed under 1000 copies/mL.
The researchers invited these 26 people to keep coming back for checkups, and 22 agreed. After a median follow-up of 36 months (range 20 to 43 months) following PRIMSTOP week 84, 6 people (27%) had to resume antiretrovirals. One of them was the single person whose viral load stayed under 50 copies/mL during weeks 84 to 108 of PRIMSTOP. At least for this person, tight early control did not translate into good long-term control.
These 6 people restarted ART after a median of 12 months (range 7 to 25 months), at a median CD4 count of 245 cells/mm3 (range 197 to 266 cells/mm3), and at a median viral load of 4.76 log copies/mL (range 3.86 to 5.44 log copies/mL).
Sixteen people did not resume ART for 30 months after stopping at PRIMSTOP week 84. At last follow-up their median CD4 count stood at 456 cells/mm3 (range 333 to 639 cells/mm3), down from a median 696 cells/mm3. This group's viral load rose a median 3.1 log copies/mL and 11 (68%) reached a load above 10,000 copies/mL. During this extended drug break, clinicians diagnosed oral candidiasis in one person and non-Hodgkin lymphoma in another.
German clinicians compared 144 acutely infected people who began treatment right after their diagnosis and 56 acutely infected people who decided not to start right away. First viral loads were significantly higher in the treated group (median above 500,000 copies/mL) than in the untreated group, though untreated people still had a high median first load of 240,000 copies/mL (P < 0.001). The first CD4 count in the untreated group stood at a median 621 cells/mm3, compared with 453 cells/mm3 in the treated group (P < 0.01).
In the treated group 98 people (68%) stopped therapy after a median 9.0 months (range 1.2 to 28.7 months). Thirty-seven of those 98 (38%) reached a CD4 count below 350 cells/mm3 and/or a viral load above 100,000 copies/mL after a median interruption of 14.3 months. In comparison 20 of 56 untreated people (36%) reached one or both of those indications to start therapy a median of 8.3 months after HIV seroconversion. This difference reached statistical significance (P = 0.02) only for people with a first viral load above 50,000 copies/mL.
The critical question here is when a person with primary infection wants to embrace the benefit and burden of antiretroviral therapy. The early-treatment group had to take antiretrovirals for 9 months on average to enjoy the 14-month break in therapy before having to start again. The deferred-treatment group may have had to start treatment faster than the early-treatment group had to resume treatment, but they didn't have to take antiretrovirals for 9 months to get to the starting line of this comparison.
References
1. Hoen B, Deveau C, Fournier I, et al. Absence of sustained benefit of HAART followed by structured treatment interruptions in primary HIV-1 infection: prolonged follow-up of patients enrolled in the PRIMSTOP (ANRS 100) trial. XVI International AIDS Conference. August 13-18. Toronto. Abstract MOPE0059.
2. Koegl C, Wolf E, Jessen H, et al. Does early treatment of primary HIV infection delay treatment indication? XVI International AIDS Conference. August 13-18. Toronto. Abstract MOPE0060.
3. Hoen B, Fournier I, Lacabaratz C, et al. Structured treatment interruptions in primary HIV-1 infection: the ANRS 100 PRIMSTOP trial. J Acquir Immune Defic Syndr 200;40:307-316.
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