OI prophylaxis guidelines may need to vary from country to country

Even though it has been used far too often as an justification to delay or deny treatment, the notion that there is something unique about the course of HIV disease and its opportunistic infections in Africa, and in South Africa in particular, is nothing to scoff at — there is ample evidence that there are significant differences. For example, factors such as the greater prevalence of TB have well-recognised affects on the HIV epidemic in Africa.

Other possible co-factors such as prevalence of malaria and other parasitic infections or the geographical distribution of various microbial organisms and viruses might also alter the pattern or order of clinical events that will be observed as people progress to late stage disease.

Treatment or prophylaxis recommendations that are taken for granted in the developed world are not always applicable in Africa or other resource limited regions and must, at times, be re-explored and revalidated in different clinical settings.

An oral session on co-infections held during the First South African AIDS Conference explored some of these issues.

Data from two presentations could affect recommendations on prophylaxis in Southern Africa. One was a report of surprisingly high rates of bacterial resistance to cotrimoxazole among South African patients enrolling in a cotrimaxazole prophylaxis trial, presented by Dr. Charles Gilks of the World Health Organisation on behalf of Dr. Nchabeleng of the University of Natal.

In 1997, two studies in Ivory Coast had shown that cotrimoxazole prophylaxis decreased morbidity and mortality in HIV infected patients there. Based on these findings, WHO recommended cotrimoxazole prophylaxis for all immune-suppressed HIV infected patients.

And yet, “there were unanswered questions,” said Dr. Gilks. “What is the basis of cotrimoxazole’s effect?” Is it the prevention of bacteraemia or the prevention of PCP and toxoplasmosis, or both? If it is at least partly due to the prevention of bacterial infections, will the same effect be observed outside of the Ivory Coast? This would depend on the susceptibility patterns of local bacteria. If it is dependent upon the anti-PCP effect, “how frequent is resistance and how do you deal with it?” said Dr. Gilks.

To answer these questions, the University of Natal has initiated an ongoing study in KwaZuluNatal to determine whether the Ivory Coast results are reproducible in South Africa and to measure cotrimoxazole resistance both at the start of the study and after two years on drug. Dr. Gilks reported data from only one of these questions: the susceptibility to cotrimoxazole of bacterial organisms in AIDS patients at the start of prophylaxis.

150 patients diagnosed with AIDS/tuberculosis were recruited for the study. Swabs from the nose, mouth, throat and rectum were cultured in a cotrimoxazole-containing medium to determine the inhibitory concentrations for all the isolates. 411 isolates with decreased susceptibility were obtained from 150 patients. 146 patients (97%) carried at least one organism with decreased susceptibility or total resistance. Patients carried a mean of two organisms with decreased susceptibility, (range 1 to 5). Of the 411 isolates, 282 (69%) were fully resistant to cotrimoxazole. In 24% of the patients, all isolates were fully resistant. Some of these fully resistant bacteria included organisms that cause serious disease and sepsis, inclduing Streptococcus pneumoniae (1), Klebsiella pneumoniae (14), Haemophilus influenzae (2), and Salmonella (1).

“The high pre-prophylaxis resistance to cotrimoxazole suggests that if prophylaxis is supposed to prevent bacterial infection, the success rate in South Africa is likely to be lower than that seen in the Ivory Coast,” said Dr. Gilks. Dr. Gilks concluded that further study is needed to determine the incidence of PCP resistance at study entry and to confirm whether cotrimoxazole prophylaxis is indeed beneficial in South Africa.

While the previous study calls into question the widespread use of cotrimoxazole prophylaxis, a second study suggests that fluconazole prophylaxis should perhaps be offered to people with HIV who develop active TB. Dr. A Grant presented compelling data suggesting that “cryptococcal meningitis is an increasingly important cause of mortality in the developing world that often occurs in the presence of TB.” It is the leading cause of death in South African gold miners with HIV. Observing a high frequency of cryptococcal disease among HIV-infected people with TB, Grant et al. conducted an observational study to investigate the association between these conditions.

The study examined risk factors for the development of Cryptococcal meningitis in miners from a gold mining company in South Africa attending a clinic providing specialised HIV care. Antiretroviral therapy was not available at that time. Cryptococcal meningitis was defined as identification of CM spp on microscopy or CSF cryptococcal antigen greater than or equal to 1:8.

1816 patients enrolled (mean age 39.5 years, mean CD4 count 377). 37 participants experienced cryptococcal disease over 1807 person-years of follow up (incidence rate [IR] 2.0 per 100 patient years). The median (range) time to episode was 3.1 months (0.1-14.5).

Factors associated with cryptococcal risk in a univariate analysis included baseline age (the highest risk was for those between 35-39), CD4s

The cause for this is unclear. Cryptococcal spp are contracted from pigeon droppings, and pigeons are reported to infest cliffs outside of the mines. It could be due to an increased susceptibility to inhaling spores during TB, or there could be a functional defect in the immune system while TB is active. “There is some evidence that risk of CM drops during TB treatment but the numbers are small at present, said Dr. Grant.”

Whatever the reason, Dr. Grant believes that “there needs to be a high index of suspicion for cryptococcal meningitis during TB. The risk may diminish with antiretrovirals or we should perhaps consider giving TB patients fluconazole prophylaxis while they are on TB treatment.”