Clinical management

This article originally appeared in HIV & AIDS treatment in practice, an email newsletter for healthcare workers and community-based organisations in resource-limited settings published by NAM between 2003 and 2014.
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Fracture patients infected with HIV infection may not warrant extra precautions against opportunistic infection

By Hayden Eastwood

Doctors treating open fractures in patients infected with HIV do not need to be more cautious about opportunistic infections compared with HIV-negative patients. The finding, presented by James Aird of Ngwelezane Hospital at the Fourth South African AIDS conference in Durban this month, follows research conducted in KwaZulu-Natal, South Africa.

Many surgeons who treat open fractures (those which result in skin breakages) are concerned that HIV-infected patients may be at higher risk of developing opportunistic infections. Furthermore, this risk of infection may depend on whether the fracture is fixed internally (by mending the fracture with artificial pins and plates) or externally (by repairing the fracture with external splints, pins or supporting structures).

There are few published articles that describe the effects of HIV on fracture healing; those that do often involve small numbers of patients and are frequently statistically insignificant. However, management of bone fractures in HIV-positive individuals is a significant clinical concern in settings where between one in five and one in three adults is infected with HIV.

A previous study suggested that a four-fold increase in infection rate arises when HIV patients have internally fixed fractures. The researchers in this study attempted to reproduce and extend this finding by comparing fractures repaired with internal and external fixation in both HIV-positive and HIV-negative patients.

The study involved co-operation from 93 patients with open fractures, who were examined in a dedicated clinic with a follow-up period of between one and five months. The socio-economic backgrounds of the individuals were recorded in order to determine possible external risk factors of infection and each patient was offered an HIV test.

Of the fracture patients, 25 were treated with external fixation and 68 with internal fixation. Twenty-four per cent of the patients tested were found to be HIV-positive, while 15% refused to be tested. Within the HIV-positive group, CD4 counts ranged between 131 and 862 (with a mean of 366). Eleven per cent of the wounds suffered a superficial infection, with a relative risk for HIV of 0.66 (0.15 to 2.9). For external fixators, 44% of the pin sites developed superficial infection that required antibiotics with a relative risk for HIV-positive patients of 1.21 (0.5 to 2.98).

These findings suggest that the risk of serious infection in HIV patients with open fractures (fixed with either internal or external fixation) may not be as high as some previous studies have suggested and, by extension, imply that HIV status does not necessarily need to affect the management of fracture patients, particularly those with higher CD4 counts.

The researchers suggest that a larger and more statistically representative study be conducted.

Reference
Aird J et al. Study into wound infection rates in open fractures treated with internal fixation, in relation to HIV co-infection Fourth South African Conference on AIDS, Durban, South Africa, abstract 473, April 2009

Incidence of Kaposi’s sarcoma rising among black South Africans

By Hayden Eastwood

The incidence of Kaposi's sarcoma is increasing amongst Black South Africans and is a growing health problem that requires urgent attention, according to work published by the University of KwaZulu-Natal at the Fourth South African AIDS Conference in Durban.

Kaposi's sarcoma (KS) is a rare cancer that is much more common in people with immunosuppression, such as those with advanced HIV infection. The condition, which is characterized in its early stages by dark skin lesions and subsequently by lesions in the mucous membranes, the lungs, the gut and the lymph nodes, is caused by infection with human herpes virus 8 (HHV-8).

Despite the association between HIV infection and KS, there is still no well established incidence estimate for AIDS-associated KS in South Africa.

The current study, which attempted to estimate this incidence, made use of anonymous administrative records for patients receiving care for KS in KwaZulu-Natal between 1983 and 2006 in public-sector oncology clinics. Age-standardised incidence rates were calculated using provincial census data for the local population in the years of 1985, 1996, 2001 and 2005. Age-specific rates, which were subject to different data constraints, were assessed for the years 1983 to 1989 (the baseline) and for 2006 (the generalised HIV epidemic).

The researchers report that age-standardised incidence rates (per 100,000 people) increased from 1.04 to 19.7 between 1983 and 2007. This compares with a standardised incidence ratio in a Ugandan HIV-positive population of 6.7 when compared to the general population.

More worryingly, the incidence rate for women during the same period increased fifty-fold, from 0.21 to 11.51. Gender-averaged figures pointed towards an incidence increase from 0.52 to 14.76. Furthermore, the age of peak incidence (the age group in which KS is most likely to occur) was shown to shift from a 55 to 60-year age bracket to a 40 to 50-year age bracket for both men and women. This was expected because HIV is more prevalent in young people than old people.

The authors stress that only public-sector patients were considered in the study. Many cases of early and late stage KS may very well have been treated by private doctors or left untreated and, if this was a common occurrence, may very well have contributed to a serious underestimation of KS incidence.

The study illustrates the alarming growth of KS as a health problem in rural South Africa. The researchers call for more resources to be directed at quantifying the problem and for better medical resources to be made available for KS sufferers.

Our newsletter HIV & AIDS Treatment in Practice published a clinical review of Kaposi’s sarcoma management in resource-limited settings in February 2008.

References
Mosam Anisa et al. Increasing incidence of Kaposi’s sarcoma in Black South Africans in Kwazulu-natal, South Africa (1983 to 2006).. Fourth South African AIDS Conference, Durban, South Africa, abstract 52, 2009.

Mbulaiteye SM et al. Spectrum of cancers among HIV-infected persons in Africa: the Uganda AIDS-Cancer Registry Match Study. Int J Cancer;118(4):985-90, 2006.

Anaemia is a risk factor for mortality in patients with AIDS

Glossary

Kaposi's sarcoma (KS)

Lesions on the skin and/or internal organs caused by abnormal growth of blood vessels.  In people living with HIV, Kaposi’s sarcoma is an AIDS-defining cancer.

anaemia

A shortage or change in the size or function of red blood cells. These cells carry oxygen to organs of the body. Symptoms can include shortness of breath, fatigue and lack of concentration.

immune reconstitution inflammatory syndrome (IRIS)

A collection of inflammatory disorders associated with paradoxical worsening (due to the ‘waking’ and improvement of the immune system) of pre-existing infectious processes following the initiation of antiretroviral therapy.

 

antibiotics

Antibiotics, also known as antibacterials, are medications that destroy or slow down the growth of bacteria. They are used to treat diseases caused by bacteria.

advanced HIV

A modern term that is often preferred to 'AIDS'. The World Health Organization criteria for advanced HIV disease is a CD4 cell count below 200 or symptoms of stage 3 or 4 in adults and adolescents. All HIV-positive children younger than five years of age are considered to have advanced HIV disease.

By Hayden Eastwood

HIV patients suffering simultaneously from anaemia and WHO stage 4 HIV disease have a 59% (or greater) chance of dying, even when opportunistic diseases like TB are being treated with antibiotics. The findings, presented at the Fourth South African AIDS Conference in Durban, suggest that anaemia is an independent risk factor that needs to be managed separately from other HIV-associated ailments.

Previous studies have shown that patients suffering from advanced AIDS can have their lives prolonged by treating opportunistic infections with aggressive antibiotic or antifungal treatment and antiretroviral therapy. Co-infected HIV-TB patients who are treated with anti-TB drugs, for example, have a much lower chance of dying (40% death rate) compared to those who don’t take treatment (60% death rate).

Anaemia is a set of symptoms, including fatigue, headaches and shortness of breath, which result from blood haemoglobin levels becoming abnormally low. People with advanced HIV often suffer from anaemia because their bodies can no longer (for a variety of reasons) produce the hormones required to stimulate red blood cell production.

Previous published work from a number of chorts in resource-limited settings has suggested that anaemia, which is not responsive to antibiotics, is a major risk factor for death in people with advanced HIV disease.

The South African research team, working at Settlers Hospital in KwaZulu-Natal, evaluated the impact of anaemia on survival in a South African cohort by collecting data about blood transfusions, haematinics (substances necessary to make red blood cells, such as iron and folic acid) and anti-HIV treatment history from people admitted to the palliative care ward.

The team found that AIDS patients with anaemia suffered a death rate of 59%. This was high compared to patients who died of causes like TB (26% death rate), sepsis (22%), HIVAN, a kidney disease developing with HIV (12%), Kaposi's sarcoma (10%), cancer (7%), dementia (7%) and other diseases (16%).

Furthermore, the average CD4 counts in anaemic patients who died were often similar to non-anaemic patients who lived, leaving doctors to suspect that anaemia, and not opportunistic infection arising from poor immunity, was a major cause of death.

In most cases, blood transfusions and intravenous Venofer (a source of iron) did not seem to reverse the anaemia. Furthermore, the levels of blood ferritin (a protein required to store iron and prevent anaemia) remained unresponsive to treatment, leaving most patients trapped in a high-risk anaemic state.

The findings provide further evidence that anaemia is an independent death-risk factor for patients suffering from advanced AIDS.

The researchers call for more money and resources to be spent on treating anaemia in people with advanced AIDS.

Reference
Jamieson C The investigation of the effects of anaemia on the outcome of patients with stage 4 AIDS. Fourth South African AIDS Conference in Durban, South Africa, abstract 408, 2009.
 

Rheumatologic symptoms after ART may be due to immune reconstitution inflammatory syndrome (IRIS)

By Hayden Eastwood

New or worsening rheumatologic symptoms that follow antiretroviral therapy may be due to immune reconstitution inflammatory syndrome (IRIS), according to findings reported at the Fourth South African AIDS Conference in Durban.

IRIS is a collection of symptoms that frequently emerge soon after antiretroviral therapy is started in HIV-positive people. IRIS is believed to result from a rejuvenated immune system mounting an inflammatory response.

Despite a well-defined case definition, there is debate within the medical community about which symptoms should fall under an IRIS classification.

British and South African researchers attempted to determine whether joint pain should be regarded as an IRIS symptom by closely monitoring the onset of joint symptoms in patients undergoing antiretroviral treatment.

The study, which was conducted in Durban, South Africa, involved 498 adult HIV-infected patients who were due to begin antiretroviral treatment at two clinics during 2006 and 2007. Participants were subjected to normal clinical health checks before treatment started and also at two, four, eight, twelve, 16, 20 and 24 weeks following the start of treatment.

Patients who reported joint symptoms were assessed clinically and alternative diagnoses of their joint pains explored. In each patient, baseline and CD4 cell counts were tracked alongside C-reactive protein (CRP), which is present in blood during inflammatory responses and which, accordingly, allows doctors to measure the extent of inflammation.

Laboratory analysis of the patients’ blood revealed a median CD4 cell count of 106 (interquartile range of 53 to 165) and a baseline viral load of 5 log (interquartile range of 4.4 to 5.6 log).

Seventy-seven (15%) of the patients reported joint symptoms before or during the study period. Of these, some were excluded as IRIS cases because alternative explanations existed for their joint symptoms. Eleven patients, for example, were found to have mechanical causes of joint pain and six were found to be suffering from the side-effects of other drug treatments. After correcting for alternative diagnoses, 23 cases (30%) remained, presumably an inflammatory side-effect of antiretroviral therapy.

The median onset period for joint symptoms occurred at eleven weeks (range one week to 22 weeks) after anti-HIV treatment started, within the normal IRIS onset period. Only one patient had elevated levels of rheumatoid factor.

The researchers highlight that joint pain is common in many HIV-TB co-infected patients during the first six months of antiretroviral treatment. In the absence of other diagnoses, these symptoms may be part of the IRIS spectrum.

Reference
Haddon L et al. Are rheumatologic symptoms after initiation of antiretroviral therapy part of the spectrum of immune reconstitution inflammatory syndrome (IRIS)? Fourth South African AIDS Conference, Durban, South Africa, abstract 410, April 2009