South African women living with HIV subtype C experience rapid CD4 cell loss

Implications for test and treat strategies
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A third of women living with HIV subtype C have a fall in their CD4 count to below 350 cells/mm3 within a year of seroconversion, investigators report in the online edition of Clinical Infectious Diseases. The World Health Organization (WHO) now recommends that antiretroviral therapy (ART) should be initiated at a CD4 count of 500 cells/mm3 and 69% of women had a CD4 count below this level within twelve months of acquiring HIV.

The study was conducted in South Africa and the investigators suggest their findings have major implications for ART programmes.

“The rapid progression observed in this cohort provides additional motivation to implement earlier ART initiation,” comment the authors. “This study suggests that earlier treatment initiation carries many benefits including the potential for major impact on individual health by increasing survival and on public health by preventing transmission.”



The transition period from infection with HIV to the detectable presence of HIV antibodies in the blood. When seroconversion occurs (usually within a few weeks of infection), the result of an HIV antibody test changes from HIV negative to HIV positive. Seroconversion may be accompanied with flu-like symptoms.


disease progression

The worsening of a disease.

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).


In HIV, different strains which can be grouped according to their genes. HIV-1 is classified into three ‘groups,’ M, N, and O. Most HIV-1 is in group M which is further divided into subtypes, A, B, C and D etc. Subtype B is most common in Europe and North America, whilst A, C and D are most important worldwide.


A variant characterised by a specific genotype.


Comparatively little is known about the rate of disease progression in people living with HIV subtype C – the dominant strain of HIV in sub-Saharan Africa. It is important to gain a clearer understanding of this question so that ART roll-out programmes in the region can be properly planned and resourced.

An international team of investigators therefore designed a study to determine the rate of CD4 cell loss among women with a known date of HIV seroconversion.

Recruitment took place between August 2004 and May 2005. The study population comprised sex workers and women reporting a high number of sexual partners. The participants were monitored for acute HIV infection at monthly or three-monthly intervals.

A total of 62 women were identified with recent HIV infection and their rate of CD4 count loss was monitored over three years.

The median age at HIV infection was 25 years. The mean CD4 count at the first post-seroconversion follow-up was 520 cells/mm3. This was significantly lower than the pre-infection count of 993 cells/mm3 (available for 23 women).

Almost a third of participants (31%) reached a CD4 count below 350 cells/mm3 six to twelve months after acquiring HIV, 44% within 24 months and 55% within 36 months.

In 2013, WHO increased its recommended CD4 count threshold for ART initiation to 500 cells/mm3. Applying this criterion would have resulted in 69% of women requiring therapy within twelve months, 79% within 24 months and 81% within 36 months.

The first mean viral load measurement after seroconversion was approximately 65,000 copies/ml. Three months after infection, rapid progressors had a significantly higher viral load compared to non-rapid progressors (72,000 copies/ml vs 13,000 copies/ml, p < 0.001).

Participants with a viral load of 100,000 copies/ml or higher three months post-infection were more likely to experience a fall in their CD4 count below 350 cells/mm3 sooner, compared to women with a lower viral load.

At month 24, 77% of women with a high viral load at the three-month follow-up point had a CD4 count below 350 cells/mm3 compared to 35% of women with a lower early viral load.

The median time to CD4 cell decline to below 350 cells/mm3 was seven months post-infection for women with a high viral load compared to 35 months for women with a low viral load.

The best predictors of CD4 decline and rapid disease progression were CD4 count three months after seroconversion (HR = 2.07; 95% CI, 1.31-3.28 per 100 cell/mm3 decrease), high viral load during early infection (HR = 3.82; 95% CI, 1.51-9.67 per 1 log10 increase) and hepatitis B virus co-infection (HR = 4.54; 95% CI, 1.31-15.69).

In contrast, slower disease progression was associated with carrying certain HLA genotypes (B*1302, B*27, B*57, B*5801, B*8101).

“We show nearly half of the clade C-infected women met our conservative definition for rapid disease progression (CD4 decline < 350 cells/mm3 within 2 years of HIV-1 infection),” comment the investigators. “This finding supports the argument of starting ART early…given the new WHO guidelines of ART initiation at 500 cells/mm3, more effort should be placed on diagnosing acute HIV infection to ensure that the large proportion of women requiring treatment within the first year of infection are not missed.”


Mlisana K et al. Rapid disease progression in HIV-1 subtype C infected South African women. Clin Infect Dis, online edition, 2014.