Restoring and maintaining a high CD4 count possible for vast majority of people living with HIV in France

Dominique Costagliola, speaking at HIV Glasgow. Image courtesy of HIV Drug Therapy Glasgow 2014 (hivglasgow.org)

A large French study has shown that the vast majority of people living with HIV who started treatment since 2000 in a national cohort achieved a CD4 cell count in the normal range within three to four years of starting treatment, while a large Italian study showed that achieving a normal CD4 count on treatment greatly reduced the risk of cancer and other serious non-AIDS illnesses.

The findings were presented last week at the HIV Drug Therapy Glasgow conference.

Reaching and maintaining a high CD4 cell count is one of the main objectives of antiretroviral therapy (ART), in order to provide patients with long-term protection against both AIDS-defining and non-HIV related diseases, commonly called co-morbidities. The CD4 recovery, expected from treatment, usually follows the suppression of viral load.

Glossary

pneumonia

Any lung infection that causes inflammation. The infecting organism may be bacteria (such as Streptococcus pneumoniae), a virus (such as influenza), a fungus (such as Pneumocystis pneumonia or PCP) or something else. The disease is sometimes characterised by where the infection was acquired: in the community, in hospital or in a nursing home.

cardiovascular

Relating to the heart and blood vessels.

comorbidity

The presence of one or more additional health conditions at the same time as a primary condition (such as HIV).

cardiovascular disease

Disease of the heart or blood vessels, such as heart attack (myocardial infarction) and stroke.

integrase inhibitors (INI, INSTI)

A class of antiretroviral drugs. Integrase strand transfer inhibitors (INSTIs) block integrase (see ‘integrase’). Blocking integrase prevents HIV from replicating.

A team of French researchers assessed CD4 cell recovery in treatment-naive patients (people who had not previously taken treatment) who had initiated ART with at least three drugs after 2000. Participants in the study were followed for between two and seven years (median 65 months). Patients also had to have a suppressed viral load nine months after the initiation of their therapy to be eligible for inclusion in this analysis. This research was based on data from the French Hospital Database on HIV.

The second objective of the research was to look at patients’ baseline characteristics that were associated with achieving a CD4 cell count over 500.

Data from 13,912 people were analysed. Their median age was 39, and two-thirds were men. When beginning ART, their median CD4 cell count was 226 and 18.5% had experienced a prior AIDS event. One-in-ten participants had hepatitis C co-infection, and one-in-ten had been diagnosed during primary HIV infection.

In the analysis, patients were stratified by CD4 cell counts at ART initiation:

  • Less than 200 – 5909 patients
  • 200-350 – 5751 patients
  • 350-500 – 2252 patients.

The proportion of patients who had a CD4 cell count above 500 cells/mm3 is shown in the table.

Baseline CD4 cell count

Year 1

Year 2

Year 3

Year 4

Year 5

Year 6

Year 7

Less than 200

8%

21%

33%

43%

52%

60%

61%

200 - 350

40%

61%

73%

81%

85%

88%

90%

350 - 500

74%

87%

91%

94%

95%

96%

97%

After five years of ART, a high CD4 cell count had been achieved by 85% of those with a baseline CD4 between 200 and 350 cells/mm3, and 95% of those with a baseline CD4 above 350 cells/mm3. Moreover, the results show that CD4 cell counts continued to increase seven years after starting antiretroviral therapy, independently of baseline levels.

Although failing to achieve a CD4 recovery was a rare outcome for patients new to treatment in this cohort, recovery took substantially longer in patients who initiated ART with low CD4 counts. After five years on treatment, only half of patients with a baseline CD4 cell count below 200 had achieved a CD4 cell count above 500 and even after seven years, almost 40% of people who started treatment late still had a CD4 cell count below 500 cells/mm3.

People with a higher CD4 count before initiating ART, as well as those who began treatment during primary infection, were more likely to have a full CD4 recovery within seven years. Moreover, individuals whose first ART regimen was an integrase inhibitor and two nucleoside reverse transcriptase inhibitors were more likely to achieve a high CD4 cell count.

CD4 cell count and serious non-AIDS events in Italy

A second study examined the relationship between baseline CD4 cell count, current CD4 cell count and the risk of developing serious non-AIDS events (SNAE) in people living with HIV in Italy.

Serious non-AIDS events (SNAE) are now known to be frequent in people living with HIV and receiving ART. The researchers grouped SNAE into two categories: infective (pneumonia, sepsis, endocarditis, meningitis) and non-infective (malignancies, chronic kidney disease, pancreatitis, cardiovascular and hepatic events).

Previously, current CD4 cell counts have been shown to be more strongly associated with infective, rather than non-infective SNAE.

The researchers included all people living with HIV who were enrolled in the Icona Foundation Study cohort in Italy. Participants were followed-up from the date of enrolment (baseline) to a diagnosis of SNAE or to the last study visit. Researchers defined “an event” as the first time one of the SNAEs occurred (therefore patients could not contribute multiple events).

In total, 10,822 patients were included, of whom 25.3% were female, 38.2% were heterosexual and 26.6% had hepatitis co-infection. Participants’ median age was 36 years.

Overall, 423 non-infective and 385 infective SNAE were included. The most frequent non-infective events were malignancies (202 cases) and the most frequent infective event was pneumonia (289).

A higher current CD4 count was associated with a reduced risk of infective and non-infective events in people who had never taken ART and those currently taking ART. However, in people who had stopped taking ART, the association was weaker.

No association was found between the baseline CD4 counts and the risk of non-infective SNAEs in people treated with ART; and when cardiovascular disease events were considered separately, there was no association with the CD4 count.

The investigators concluded that – in contrast to what is seen in people who have never taken ART – in people taking ART, non-infective SNAEs are predicted by current but not baseline CD4. These findings suggest a key role of immune restoration in preventing these events.

Taken together, the findings of these large French and Italian studies underline the importance of early diagnosis and initiation of treatment for CD4 cell count recovery and for protection from serious non-AIDS illness in people living with HIV.

References

Costagliola D et al. CD4+ cell count recovery in naïve patients initiating ART, who achieved and maintained plasma HIV-RNA suppression. J Int AIDS Soc 17 (3): 2 (abstract 0113), 2014.

Madeddu G et al. CD4 cell count and the risk of infective and non-infective serious non-AIDS events in HIV-positive persons seen for care in Italy. J Int AIDS Soc 17 (3): 14 (abstract 0312), 2014.