Research has shown that effective antiretroviral therapy (ART) decreases the risk of sexual transmission of HIV by suppressing blood and genital HIV RNA to undetectable levels by 24 weeks. However, the virus is still detectable in genital secretions during the first few weeks of ART, making residual risk of HIV transmission possible during the time between ART initiation and systemic viral suppression, explains Andrew Mujugira, MD, PhD.
In a previous study of genetically linked HIV transmissions, Dr. Mujugira’s colleagues found that only one of 103 such transmissions occurred from an infected partner on ART. “The lone case was a female-to-male transmission that occurred soon after the infected partner started ART,” explains Dr. Mujugira.
A Secondary Analysis
For a study published in the Journal of Acquired Immune Deficiency Syndromes, Dr. Mujugira and colleagues sought to determine HIV transmission risk during this period. “We conducted a secondary analysis of data from the Partners PrEP Study,” he says. “This was a randomized trial of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention in 4,747 heterosexual HIV serodiscordant couples. The study was conducted at nine clinical trial sites from 2008 to 2012. A total of 1,817 HIV-infected people with HIV-uninfected partners initiated ART during the study.”
HIV transmission risk was assessed using multiple biologic and behavioral measures:
- Time to first viral suppression in blood plasma.
- Persistence of HIV RNA in endocervical secretions and semen plasma.
- Frequency of condom-less sex (by self-report).
- Pregnancy incidence (in couples with HIV-infected and uninfected women).
- Phylogenetically linked HIV transmission within the couple.
The study team found that the cumulative probabilities of achieving blood viral suppression—defined as less than 80 copies/mL—were about 65% at 3 months, nearly 85% at 6 months, and approximately 89% at 9 months after starting ART. Among partners who were initially uninfected, HIV incidence per 100 person-years was 2.08 prior to ART, 1.79 during the first 6 months of ART, and 0.0 after more than 6 months of ART. Condom-less sex was reported in more than 10% of visits. During the first 6 months of ART, the incidence rate for pregnancies was 8.80 per 100 person-years.
“Our findings show the HIV transmission risk remained high during the first 6 months of therapy,” says Dr. Mujugira (Figure below). “In fact, 35% and 15% of HIV-infected persons had not yet achieved blood viral suppression after 3 and 6 months of ART, respectively. This suggests that there is a residual risk of HIV transmission soon after ART initiation. However, no HIV transmissions were observed after 6 months of ART, a finding that has been reported in other studies.”
The researchers detected HIV RNA in 12% of endocervical swabs and 21% of semen plasma samples during the first 6 months of ART. The median quantities of HIV RNA detected in semen plasma and endocervical swabs were 794 copies/mL and 1,288 copies/mL, respectively. “Whereas genital HIV RNA levels lower than 1,000 copies/mL are associated with low risk of heterosexual HIV transmission, the presence of levels above that threshold indicates residual HIV infectiousness,” adds Dr. Mujugira. “Interestingly, the three women in our study who transmitted HIV to male partners while on ART did so within the first 150 days of starting therapy.”
Monitoring & Counseling
In light of the study findings, Dr. Mujugira recommends that clinicians closely monitor viral loads after initiating patients on ART. “Clinicians should counsel serodiscordant couples about residual risk of HIV transmission during the first 6 months of therapy,” he says. “We also recommend that couples use additional preventive precautions like PrEP and condoms at least until viral suppression in blood and genital secretions is achieved in the infected partner. Importantly, patients should be informed that although the risk of HIV transmission after virologic suppression is very small, it is not zero.”
Readings & Resources (click to view)
Mujugira A, Celum C, Coombs R, et al. HIV transmission risk persists during the first 6 months of antiretroviral therapy. JAIDS. 2016;72:579-584. Available at
Quinn T, Wawer M, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med. 2000;342:921-929.
Donnell D, Baeten J, Kiarie J, et al. Heterosexual HIV transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet. 2010;375:2092-2098.
Reynolds S, Makumbi F, Nakigozi G, et al. HIV transmission among HIV discordant couples before and after the introduction of antiretroviral therapy. AIDS. 2011;25:473-477.