Unsuccessful post-exposure prophylaxis may still result in weaker HIV infection and lower viral load

[Guest guest]

HIV post-exposure prophylaxis, even when it fails to prevent infection, may

still have benefits, a case report in the Journal of Acquired Immune Deficiency

Syndromes suggests.

The case report involved a patient who received post-exposure prophylaxis (often

called PEP) with Truvada (FTC and tenofovir). Although this treatment failed to

prevent HIV infection, the patient did have a well-preserved immune function and

a lower viral load than would be expected. He was therefore much less infectious

than the average patient during acute infection.

The patient was a 38-year-old gay man in New York, who first came to a clinic on

26 September 2006 reporting that he had had unprotected receptive anal sex with

multiple partners during the previous 48 hours. He was treated with Truvada as

post-exposure prophylaxis. During the period on this treatment, on 24 October,

he reported more episodes of risky sex and his course of post-exposure

prophylaxis was therefore extended. He stopped taking it on 7 November. He

tested HIV-negative on that date.

He reported a third episode of risky sex on 28 November and was restarted on

Truvada. On 18 December, three weeks later, he tested HIV-positive. He was

adamant that he had had no risky sex during the period when he was not taking

post-exposure prophylaxis, which he finally stopped taking on 29 December.

His first two viral load tests were performed on 22 December – when he was still

receiving treatment with Truvada – and on 9 January 2007. His viral load was

very low, with 213 and 647 copies/ml in these two tests respectively. His viral

load increased after this but never exceeded 3500. His CD4 count was a very high

1800 cells/mm3 on 22 December, just after his first positive HIV antibody test,

and then fell to about 750. At no time did he have the high viral load and low

CD4 count typical of acute HIV infection, and he had no HIV seroconversion

symptoms.

The patient's antibody response developed much more slowly than normal. Some

basic tests were performed on his HLA genes, which determine susceptibility to

HIV infection, but he had no genetic mutations associated with a lower viral

load or less virulent course of HIV infection.

Samples were taken of his intestinal mucosa and further tests were performed on

the T-cells in his gut lining. These showed a third of the T-cells in his

intestinal lymphoid tissue were CD4 cells. This is a lower proportion than in

HIV-negative individuals (typically 56%), but twice as many as in subjects with

acute HIV infection (16%). He also had considerably fewer activated CD4 and CD8

cells than the average person with acute infection, indicating a much lower

level of generalised immune activation and gut inflammation.

One theory of how HIV causes AIDS is that the initial destruction of CD4 cells

and immune hyperactivation in the gut, from which the body never completely

recovers even under HIV therapy, eventually depletes the immune system.. A

better-preserved gut immune system may therefore lead to slower progression to

AIDS – as does a lower viral load.

Encouragingly, despite the patient contracting HIV while taking Truvada, there

was no evidence of resistance to either FTC or tenofovir, even using the most

sensitive resistance tests.

The authors write that the patient’s HIV infection was more attenuated (weaker)

than usual and that this was probably related to the antiretroviral therapy he

was taking.

They add that the findings of lower viral load and CD4 cell depletion could

“have a very beneficial effect on the spread of infection…and likely reduce the

probability of subsequent forward transmission " .

They comment: “It is important to emphasise that this case report represents

‘real-world’ use of antiretroviral drugs to prevent infection. It is likely that

even in the best of circumstances, adherence will be intermittent and patients

will…stop and start from time to time based on behaviours and perceived risk as

was the case here.”

They conclude that this cases strongly supports “continued investigation of the

use of antiviral agents as a means to reduce HIV transmission” in a situation

where “the prospect of an effective vaccine remains distant” and microbicides

“have questionable applicability to MSM transmission..”

Reference

Prada N et al. Drug-susceptible HIV-1 infection despite intermittent fixed-dose

combination tenofovir/emtricitabine as prophylaxis is associated with low-level

viremia, delayed seroconversion, and an attenuated clinical course. Journal of

Acquired Immune Deficiency Syndromes 49(2):117-122. 2008.

Kailash Karale,

Mobile: 9923103092

Research Scholar,

Department Of Biochemistry,

RTM Univ. Nagpur.

e-mail: <kailash_karale@...>