Antiretroviral Therapy for the Prevention of HIV-1 Transmission

Christian Deaton, Mercer University College of Pharmacy

Combination antiretroviral therapy (ART) is suggested to decrease the replication of human immunodeficiency virus type 1 (HIV-1) and improve the survival of infected persons.  Lower levels of plasma HIV ribonucleic acid (RNA) have been associated with decreases in the concentration of the virus in genital secretions. [1]

It is suggested that the risk of HIV transmission is low when an individual’s viral load is below 400 copies per milliliter, but the threshold below which transmission of the virus becomes impossible is unknown. [2]

The effect of the timing of the initiation of ART on clinical and microbiologic outcomes has been unclear in evaluations of the benefit of therapy and of the associated short and long-term complications and costs. It has been suggested that ART was typically delayed until a patient’s cluster of differentiation 4 (CD4+) count fell below 200 cells per cubic millimeter, which led to frequent opportunistic infections. [3]

Antiretroviral Therapy for the Prevention of HIV-1 Transmission  [4]
Design Randomized, controlled trial; N= 1,763
Objective To determine the effect of ART on the transmission of HIV-1 from infected persons to their sexual partners
Study Groups Early ART; n= 886

Delayed ART; n= 877

Methods Human immunodeficiency virus type 1 serodiscordant couples were randomly assigned in a 1:1 ratio to either an early or delayed strategy for receipt of antiretroviral therapy.
In the early-therapy group, antiretroviral therapy was initiated in the partner with HIV-1 infection at enrollment. In the delayed-therapy group, therapy was initiated after two consecutive measurements in which the CD4 count was 250 cells per cubic millimeter or less or after the development of an illness related to the acquired immunodeficiency syndrome (AIDS).
Duration May 2010 through May 2015
Primary Outcome Measure Diagnosis of genetically linked HIV-1 infection in the previously HIV-1– negative partner
Baseline Characteristics
  HIV-infected; n= 1,763 Partners; n= 1,792
Females, n 873 863
Age 26-40, n 1,103 1,063
North America, n 278 284
No schooling, n 170 189
Single, n 87 96
Hepatitis- B virus, n 94 0
Gonorrhea, n 102 74
Syphilis, n 144 103
Results Human immunodeficiency virus type 1 infections were documented in 78 (4%) partners during the course of the trial; 19 (2%) in the early-ART group, and 59 (6%) in the delayed-ART group (p< 0.05).
Adverse Events Common Adverse Events: infections (14%)
Serious Adverse Events:  metabolism and nutrition disorders (5%)
Percentage that Discontinued due to Adverse Events: (4%)
Study Author Conclusions Successful treatment of HIV- 1 is a highly effective tool for the prevention of sexual transmission of the virus.

The study revealed that, when compared to delayed ART, the use of early ART resulted in fewer occurrences of new HIV-1 infections in the partners.  Limitations of the study centered around the patient population, as the study focused on stable HIV-1 discordant couples who may not be entirely representative of the general population.  Contraception in the form of condoms was provided to all of the couples, which could likely have resulted in low incidence of HIV-1 transmission.  Also, some participants received trimethoprim-sulfamethoxazole and isoniazid prophylaxis at the discretion of the investigators, which could have reduced the degree of benefit observed with early ART.

 

References

  1. Ray M, Logan R, Sterne JA, et al. The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals. AIDS 2010. 24:123-137
  2. Das M, Chu PL, Santos GM, et al. Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco. PLoS One. 2010;5(6):e11068
  3. Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N Engl J Med. Mar 30 2000;342(13):921-929
  4. Cohen MS, Chen YQ, Mccauley M, et al. Antiretroviral Therapy for the Prevention of HIV-1 Transmission. N Engl J Med. 2016;365(6):493-505.

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