The World Health Organization current recommendations for HIV patients state that “antiretroviral therapy (ART) should be initiated in everyone living with HIV at any CD4+ cell count.” The ART cocktail of drugs has proven effective at suppressing HIV’s pandemic spread and the number of infected cells inside a person’s body.That number, the cluster of differentiation 4 (CD4+) count, can mean life or death for HIV patients.The worse the count, the more cells HIV can spread into, destroying a person’s immune system and ravaging their bodies before death.
In sub-Saharan Africa, roughly a quarter of HIV infected individuals have severe immunosuppression, with CD4+ counts far worse than the average patient’s count.Research shows that approximately one in every 10 such patients dies in the first three months of ART therapy.Like any HIV/AIDS patient, the causes of death are multifaceted, with major problems including tuberculosis, bacterial infection, and other viruses.These infections appear to be exacerbated by ART therapy initiation and the “immune reconstitution inflammatory syndrome (IRIS)” which it often brings about.Those infections, alongside abysmal CD4+ counts and unhealthy Body-Mass Indices have wrought havoc upon HIV patients seeking the universally suggested treatment for their incurable disease.More must be done.
New research from the REALITY Trial Team suggests more can be done.The team, led by Drs.James Hakim and Victor Musiime, found that enhanced antimicrobial prophylaxis treatment combined with ART reduced mortality rates in adults and children with catastrophic CD4+ counts.Their findings, from a trial enrolled in Uganda, Zimbabwe, Malawi, and Kenya over the period from June 2013 to April 2015 saw a marked decrease in the number of patients killed by HIV who received the enhanced antimicrobial prophylaxis in comparison to those who received standard prophylaxis.
Most notably, the REALITY trial showed that “ the relative rate of death at 24 weeks was 27% lower among those who received an enhanced antimicrobial prophylaxis package than among those who received trimethoprim–sulfamethoxazole alone (standard prophylaxis) for 12 weeks.” at 48 weeks, “Benefits were maintained” with a 24 percent discrepancy between the mortality rates of those with enhanced antimicrobial prophylaxis and those being given the standard prophylaxis.
In addition to a reduced chance of death, “Patients who received enhanced prophylaxis also had a significantly lower rate of hospitalization, WHO stage 3 or 4 events, IRIS-compatible events, tuberculosis, and cryptococcal and candida infections; the rate of presumptive bacterial infection was similar in the two groups.”
REALITY stands for the Reduction of Early Mortality in HIV-Infected Adults and Children Starting Antiretroviral Therapy.
The trial team notes that “The cost of enhanced prophylaxis ranged from $8 to $34 across trial countries, making the potentially lifesaving treatment relatively affordable.At an $8 price point, “the cost per quality-adjusted life-year falls within recently published cost-effectiveness thresholds for even the lowest-income countries.” despite their relative accessibility, the REALITY team also found that “drug costs varied by a factor of 10, which highlights the importance of ensuring that all countries can access drugs at the lowest prices.”
During their trial, all patients began ART with two nucleoside reverse-transcriptase inhibitors and one non-nucleoside reverse-transcriptase inhibitor.They were then randomly assigned in a 1:1 ratio to initiate open-label enhanced antimicrobial prophylaxis or standard prophylaxis.Enhanced prophylaxis consisted of a single dose (400 mg) of albendazole, 5 days of azithromycin (500 mg once daily), 12 weeks of fluconazole (100 mg once daily), and 12 weeks of a fixed-dose combination of trimethoprim–sulfamethoxazole (160 mg of trimethoprim and 800 mg of sulfamethoxazole), isoniazid (300 mg), and pyridoxine (25 mg) as a scored once-daily tablet (total, three tablets per day for 1 to 5 days, then two pills per day for 12 weeks).Doses were halved for children younger than 13 years of age, except for albendazole.Standard prophylaxis consisted of trimethoprim–sulfamethoxazole alone.”
The patient participation portion of the trial lasted 48 weeks.Patients were examines by nurses at weeks 2, 4, 8, 12, 18, 24, 36, and 48.The same examinations included inquiries to trial adherence and the dispensing of more trial drugs.In addition, physical examinations, kidney and renal function evaluations, and CD4+ counts were conducted during the trial.
Unfortunately, the primary outcome at 24 and 48 weeks from the start of the trial was death.Other patients were hospitalized, had contracted tuberculosis or other infections, or suffered weight loss and other adverse effects.
The REALITY Team concludes that the enhanced prophylaxis they tested ought to be included in ART counseling for HIV infected people with abominable CD4+ counts.Their studies found a significant decrease in mortality rates and the authors note that the drug “is relatively inexpensive, has a low pill burden and an acceptable side-effect profile, and would be easy to implement at primary health centers since it relies only on screening for clinical symptoms and testing of CD4++ counts to identify asymptomatic patients with advanced HIV infection.”