Patients who start treatment in the first few months after HIV infection experience rapid and long-lasting declines in viral load and maintain high CD4 cell counts, according to the results of a five-year study published in the 1st April edition of Clinical Infectious Diseases.
The study found that there were no differences in treatment response in patients starting therapy before or after seroconversion. In addition, patients starting with a protease inhibitor- or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination had similar responses to early treatment.
Current guidelines recommend delaying the start of HIV treatment until CD4 cell counts have fallen to below 350 cells/mm3. However, some experts believe that starting treatment in the first six months after infection may be beneficial, through preventing the death of CD4 T-cells that can help the immune system kill HIV, as well as limiting the evolution of different HIV strains in the body and the storage of HIV in viral ‘reservoirs’.
To assess the long-term effects of early treatment, investigators from Boston examined the responses of 102 HIV-positive patients who started treatment within twelve months of infection. Almost all of the patients were white gay men.
Over a median follow-up of 40 months, 99 (97%) of the patients achieved a viral load below 50 copies/ml. Undetectable viral loads were achieved after a median of 11.1 weeks and were maintained by 91% of the patients after a year’s treatment and 97% after eighteen months.
“Time to virological suppression in subjects with acute HIV-1 infection is comparable to that expected in chronically infected persons, despite the fact that persons with acute infection typically have higher initial virus load,” the investigators write.
The time to achieve an undetectable viral load was similar in patients starting with protease inhibitor- and NNRTI-based treatment regimens (p = 0.25). Fifty-eight (57%) of the patients were taking a protease inhibitor and 41 (40%) were taking an NNRTI.
There were also no differences in the time to undetectability in patients starting treatment before and after seroconversion, when the body begins to produce antibodies against HIV. This occurred despite viral loads being significantly higher in the patients who had not seroconverted (5,610,000 vs. 382,000 copies/ml, p
Forty-one (40%) of the patients started HIV treatment in ‘acute’ infection before seroconversion, while 55 (54%) had seroconverted when they started treatment. Test results to check for seroconversion were unavailable for six patients.
CD4 cell counts also increased at similar rates in both pre- and post-seroconversion groups, rising from a median of 484 cells/mm3 at the start of the study to 702 cells/mm3 after 12 months. In the patients remaining on treatment, the median CD4 cell count rose to a median of 842 cells/mm3 after five years.
CD4 cell count gains were also similar in the pre- and post-seroconversion groups. However, after twelve months of treatment, patients in a comparable group of 208 untreated patients from the Multicenter AIDS Cohort Study had lower CD4 cell counts than those in theis study (p = 0.01).
Side-effect rates were similar to those expected: 11% of the patients experienced gastrointestinal problems, 7% had raised blood fats, 4% had rash and 4% had kidney stones.
“Early treatment of HIV-1 infection is well tolerated and results in rapid and sustained virological suppression,” the investigators conclude. “Preservation of CD4 cell counts may be achieved with early therapy, independent of seroconversion status.”
Despite these findings, the investigators point out that the benefits of early treatment must be balanced against the risks of drug side-effects, the development of resistance and treatment failure, as well as the effects of long-term treatment on quality of life.
“Whether initiation of early therapy should be standard of care for those with acute or early HIV-1 infection is unknown, and although this non-randomised study is not designed to answer that question directly, the long-term follow-up of this relatively large cohort provides a useful framework on which to base clinical expectations when early therapy is initiated,” they conclude.
“However, the results must be viewed in context of the relative risks of antiretroviral exposure and lack of proven long-term clinical benefit,” they add. “Initiation of early therapy years before a patient would otherwise meet treatment criteria results in significantly prolonged exposure to antiretroviral drugs and the risks inherent to these drugs.
“The relative advantages of early therapy must be carefully weighed against the disadvantages.”
Kassutto S et al. Longitudinal analysis of clinical markers following antiretroviral therapy initiated during acute or early HIV type 1 infection. Clin Infect Dis 42: 1024 - 1031, 2006.