Many HIV transmissions in sero-discordant couples occur when the HIV-infected partner has a high CD4 count and may therefore be ineligible for antiretroviral therapy (ART) in settings where guidelines recommend treatment at CD4 counts below 500 or below 350, investigators report in PLOS ONE. The research also showed that a significant proportion of transmissions in couples were not genetically linked, indicating the infections were acquired through sex with someone other than the HIV-infected regular partner.
“Close to the time of transmission, more than 50% of transmitting partners have a CD4 count of > 350 cells/mm3, and approximately a third have a CD4 count of > 500 cells/mm3,” comment the authors.
These findings have implications for expanded use of ART for prevention – often called “test and treat.” There is now overwhelming evidence that patients taking ART who have an undetectable viral load are extremely unlikely to infect their sexual partners. Guidelines issued by the World Health Organization (WHO) in 2013 recommend ART for all patients with a CD4 count below 500 cells/mm3; patients in a relationship with an HIV-negative partner are also recommended to initiate treatment, regardless of CD4 count.
New WHO guidance issued in September 2015 recommended treatment for all people living with HIV, regardless of CD4 cell count.
Investigators from the International AIDS Vaccine Initiative (IAVI) wanted to estimate what proportion of transmissions in sero-discordant relationships would be prevented by the 2013 WHO CD4 guidelines. They therefore analysed data collected from 4705 couples in Zambia, Uganda and Rwanda. The couples were recruited between 2006-2011 and received condoms and counselling on HIV prevention. The uninfected partners were tested at least every three months for HIV infection. When a new HIV infection was detected, blood samples were taken from both partners to see if the transmission was genetically linked. The estimated date of infection for the new case was calculated based on testing history. This date was linked with the CD4 count of the already infected partner. ART was initiated by the HIV-positive partners according to national guidelines.
A total of 443 incident infections were documented. Testing to determine genetic linkage was performed in 374 couples and 273 (73%) of transmissions were shown to be genetically linked.
“Our study reinforces the prevalence of unlinked transmissions,” note the investigators. “While the 2013 WHO Guidelines recommend initiating ART in the positive partner of a serodiscordant couple, our study finds that approximately one quarter of transmission events occur outside the established relationship.”
Analysis was then restricted to the couples with genetically linked transmissions.
CD4 counts in the transmitting partners were measured a median of 56 days after the estimated date of infection. The median CD4 count was 339 cells/mm3. Approximately half of transmitting partners had a CD4 count above 350 cells/mm3 (the pre-2013 threshold for the initiation of ART) and 25% had a CD4 count above 500 cells/mm3.
Viral load data were available for 93% of the linked transmitters. In ten it was undetectable due to ART initiation. “These ten transmitters had initiated ART after the transmission event, but prior to enrollment in this study; viral linkages were done on older, archived samples,” emphasise the authors.
Median viral load at the time of transmission was 69,500 copies/ml. Viral load was significantly lower among patients with a CD4 count above 500 cells/mm3 at the time of transmission compared to patients with a lower CD4 count (17,800 copies/ml vs. 102,500 copies/ml; p < 0.001). Similarly, a CD4 cell count above the 350 cells/mm3 at transmission was associated with a lower viral load than a CD4 cell count below this level (41,865 copies/ml vs. 115,000 copies/ml; p < 0.001).
“Our study shows that a significant proportion of HIV transmission occurs above the current CD4-based eligibility guidelines while the index partner may still be healthy and less inclined to adhere to treatment. A significant proportion of transmissions also occurs through sex with persons other than one’s regular partner,” comment the authors.
“These findings reinforce the importance of strengthening prevention of onward transmission in HIV infected individuals through early diagnosis, treatment and linkage to care,” they conclude. “Regular testing of couples together followed by prompt treatment of the HIV infected partner is an efficient and workable solution to minimizing the number of persons who are unknowingly in jeopardy because their spouse is HIV infected.”
Karita E et al. High transmitter CD4+ T-cell count shortly after the time of transmission in a study of African serodiscordant couples. PLOS ONE 10(8): e0134438. doi:10.1371/journal.pone.0134438.