Important note: Information in this article was accurate in July 2003. The state of the art may have changed since the publication date.
Treatment Issues: Newsletter of Experimental AIDS Therapies - Volume 17, Number 7-8, July / August 2003
Bob Huff
The descriptions below relate experiences treating adults with antiretroviral (ARV) medicines in Sub-Saharan Africa and were presented at the 2nd IAS Conference on Pathogenesis and Treatment, Paris.
Seventeen abstracts described clinical outcomes, adherence, and costs of treating 2442 adult patients in 10 African countries. In addition to these, a number of other papers discussed treatment experiences in Asia and Latin America. Most studies were retrospective chart reviews; no randomized treatment trials were reported. Numbers refer to published abstracts; full references at end of article.
Abstract 112 — A treatment program in two hospitals and 10 clinics in the Chiradzulu district, Malawi run by the Ministry of Health and Médecins Sans Frontières (MSF) reported on treating 464 adults since August 2001 with an NNRTI-based regimen. From a baseline of 109, median CD4 cell counts/mm3 increased by 142 at 6 months and by 133 at 12 months. During the period 64 patients died, 15 were lost to follow-up, 4 were non-compliant and 9 went off treatment due to toxicity or OI treatment. At time of last visit, 93% reported taking at least 80% of their prescribed therapy.
Abstract 629 — The Nigerian national treatment program reported on the 12, 24 and 36-week experience of 74 patients receiving generic nevirapine, lamivudine and stavudine at three centers during March to December, 2002. Women comprised 35% of the patients. The mean CD4 cell count/mm3 increased from 214 at baseline to 298 at week 12, and 348 at week 24. Median weight increased from 51.7 kg at baseline to 55.7 kg at week 12, 63.6 kg at week 24, and 62.7 kg at week 36. At baseline, 20.8% had TB and one patient died from TB within one week of starting treatment. The most common adverse events were peripheral neuropathy and rash. Cost was identified as a barrier to regular follow-up.
Abstract 636 — The Benin national treatment program conducted a chart review to assess characteristics of 448 patients who were receiving ART during a period between December 2001 and February 2003. A PI-containing regimen (indinavir or nelfinavir) was prescribed for 55% and an NNRTI regimen (efavirenz) for 45%. Women comprised 47% of those reviewed. Most patients were infected with HIV-1 (98.4%) with 0.6% having HIV-2 and 1% having both. BMI was less than 18.5 for 35%. The most frequent OIs were wasting, 86%; oral candidiasis, 49%; and dermatitis, 46%. TB was reported in 4% of patients. The delay from diagnosis to treatment was less than 6 months in 56%; between 6 and 12 months in 14%; from 1 to 2 years in 18% and over 2 years in 12%.
Abstract 668 — A company-sponsored treatment program for employees of the Heineken brewery in Braudi, Burundi reported the costs and benefits after 18 months experience treating 31 persons. Hospitalizations declined from an average of 20 per year prior to ART to 10 in 2001 and 6 in 2002. Deaths declined from 11 prior to ART to 2 in 2001 to 1 in 2002. Program costs were almost completely recovered by savings in medical care.
Abstract 686 — A treatment project at a military hospital in Yaounde, Cameroon reported on the 24-month experience of a pilot program treating 117 persons with a nevirapine-based regimen. Nelfinavir was substituted in 5 cases and efavirenz in 4 cases. The median length of follow-up was 10.5 months. Women comprised 69% of the patients. The median CD4 cell count/mm3 increased from 151 at baseline to 250 at 12 months. Viral load became undetectable in 85.2% of cases. The median BMI increased from 23.2 to 25.2. Eleven patients changed treatment due to adverse events and 1 due to nevirapine resistance. Nine patients died, with a median time to death of 9 months.
Abstract 690 — A clinical research center in Kampala, Uganda assessed adherence in 28 persons starting treatment with Triomune (generic NVP/3TC/D4T) using multiple techniques including self-report, visual analog scale (VAS), MEMS and unannounced pill counts. Patients were followed for 1 to 6 months (mean 3.1). Results from the various techniques were well correlated with each other; mean adherence ranged from 87% to 91%.
Abstract 693 — A clinical research center in Kampala, Uganda reported on therapeutic responses to a regimen containing efavirenz, zidovudine and lamivudine in 11 patients with non-B subtype HIV-1 (A, D), many with baseline viral loads above 100,000 copies/mL. At 12 weeks, 89% were below detectable levels of HIV RNA; at 31 weeks, 71% were undetectable. At 31 weeks the median CD4 count had increased by 183 cells/mm3.
Abstract 697 — A clinical research center in Lagos, Nigeria reported on 24-week experience treating 226 persons with generic nevirapine, lamivudine and stavudine. Median viral load decreased from 4.7 log copies/mL at baseline to 2.7 at week 24. Median CD4 count increased by 170 cells/mm3 and median BMI increased from 21.5 to 23.8. Adherence was reported as “good” in 74% of patients.
Abstract 700 — A care center in Pointe-Noire, Congo conducted a medical chart review of 49 patients who had received ART during a period from April 2002 to January 2003. The majority (65%) received a PI-containing regimen and 35% received an NNRTI-regimen. The mean CD4 cell count/mm3 rose from 97 to 215 at six months; the proportion of patients with CD4 below 50 fell from 45% to 4%. Mean patient weight increased by 4.5 kg. Seven patients had side effects that required a change in treatment. Side effects included disabling peripheral neuropathy and acute pancreatitis.
Abstract 701 — Three primary care facilities in the South African township of Khayelitsha run by MSF and the provincial government reported on clinical outcomes for 288 adults who have received ART since May 2001. Most patients started treatment with CD4 counts below 50 cells/mm3. An 18-month survival estimate was 85%. Those starting treatment with CD4 under 15 cells/mm3 had poorer survival outcomes.
Abstracts 705 and 1118 — A hospital pharmacy in Dakar, Senegal assessed adherence and causes for ART interruption in 158 adult patients over a three-year period. NNRTI-based regimens comprised 51% of prescriptions; PI-based regimens, 43%; dual therapy, 4%. Ten percent of participants died and 2% withdrew. High adherence was defined as mean monthly adherence of 95% or greater. The proportion of highly adherent patients decreased as the duration of treatment exceeded 12 months, as the monthly cost of treatment exceeded 15 euros ($17), or with the use of PI-containing regimens in patients with advanced disease.
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Access to Care through Research: After the love is gone In 1988, New York ACT UP treatment activist Jim Eigo argued, “For the person with no other options, a research study means access to healthcare.” This was a time in the U.S. when the only way to get experimental treatments to prevent certain deadly opportunistic infections was by joining a clinical trial. The activist critique of the coercive nature of such research led to a revolution in drug development and clinical trial practice, including the assurance of active controls and the innovation of expanded access programs. The availability of marketed and experimental treatments has improved considerably in the U.S. since then, at least for those who participate in the healthcare system. But in many resource-poor parts of the world, a research project may be the only way to access lifesaving HIV healthcare — with or without sophisticated antiretroviral medications. One of the central ethical questions about performing research in resource-limited settings is what happens once the research is complete, recognizing that the influx of money, skills and opportunities that come along with Western-supported research can profoundly affect quality of life and expectations in a place with few services. It’s generally agreed that research projects should strive to leave behind improved capacity to continue the benefits of research-associated services, but the reality of what happens when the clinic closes is not often reported. A study recently detailed what happened to participants when a long-term research project that provided primary health care for participants in Lusaka, Zambia closed for seven months. During the study, beginning in 1995 and continuing with one break until 2002, serodiscordant couples were enrolled and followed at three month intervals. The study has previously reported that counseling and testing reduces the incidence of HIV transmission in discordant couples by two-thirds. Couples who entered the study were given primary healthcare at the research clinic, which was lost when the study was interrupted. In the report about the seven-month closing, death rates and HIV and syphilis incidence were compared before, during and after the closing during the period between December 1988 and June 1999. After the study reopened, 531 participants (about 75% of those enrolled when the study was stopped) returned and answered questions about their experience during the closing. Most (82%) respondents reported continued condom use and the incidence of new HIV and syphilis infections during the closure did not differ from rates before or after. Yet the majority of participants reported that the closing had a negative impact on them, primarily due to the withdrawal of medical services. Most strikingly, the death rate among HIV-positive participants doubled from 6.7/100 patient years (PY) before the closing to 12.4/100 PY during the closing, then went back to 7.5/100 PY after the study reopened. This finding suggests the crucial role that medical management can have on the outcome of HIV infection, even in the absence of treatment. It also underlines the importance of assuring the sustainability of interventions that accompany research projects and for planning for the transition of study participants to alternative sources of healthcare when project funding ends. Shutes E. What happens when a research project closes: HIV incidence, mortality, and perceptions in a couples’ cohort in Lusaka, Zambia. The 2nd IAS Conference on HIV Pathogenesis and Treatment, Paris, 2003. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 111. |
Abstract 759 — A hospital in Maun, Botswanna evaluated predictors of adherence with a review of 176 randomly selected patient records of individuals who had received ART for 3 months or more. Adherence measures included 7-day recall questionnaires and pill counts, which were validated with pill identification tests, interviews and monthly pill calendars. Overall, monthly average adherence was 24.9 adherent days per month (83%). Factors that promoted adherence were adherence partners, pharmacy counseling and pill counts. Non-adherence was attributed to forgetting, lack of access, and lack of privacy.
Abstracts 1212, 1213, 1216 — The Botswanna national ARV therapy program performed a retrospective chart review to analyze the experience and outcomes of the first 306 people to receive ART in Gaborone beginning in January 2002. All HIV-positive adult citizens of Botswanna with CD4 counts below 200 cells/mm3 are eligible to receive an NNRTI-based regimen for free, containing either nevirapine (47.5%) or efavirenz (52.4%) plus Combivir. Women comprised 57% of the patients. At baseline the mean CD4 count was 81 cells/mm3 and mean viral load was 5.65 log copies/mL. The median time of follow-up was 283 days. CD4 cell count/mm3 increased by 166 at six months and by 204 at nine months. Viral load fell below 400 copies/mL in 84.5% of patients at six months. Anemia (grade 3 or 4) occurred in 8% of those receiving Combivir; four patients died (mean time to toxicity 11.6 weeks). Severe nevirapine-associated rash occurred in 3.42% (mean time to toxicity 28 days). Nevirapine-associated hepatitis developed in 2.7% with two deaths (mean time to toxicity 12.6 weeks). Efavirenz-associated CNS complications were reported in 4.45%. The overall death rate to February 2003 was 10.7% (33 of 306) with an average time to death after starting treatment of 2.4 months. Of those who died, 72% were women. The overall baseline CD4 count of patients who died during the period was 60 cells/mm3 (66% were below 50). The causes of mortality among the 33 patients was wasting with chronic diarrhea (21.2%); wasting without chronic diarrhea (9%); pulmonary TB (18.1%); AZT-induced anemia (12.1%); nevirapine-induced hepatitis (3%); cryptococcal meningitis (9%); TB meningitis (6%); Kaposi’s sarcoma (9%); PCP (3%); pseudomonas pneumonia (3%); non-AZT-induced anemia (3%); and suicide (3%). The authors note that limited blood supply for transfusion are reflected in the high rate of AZT-associated anemia. More frequent monitoring of hemoglobin for patients on AZT may also be beneficial.
Abstract LB53 — The incidence of severe morbidity among members of a research cohort in Abidjan, Cote d’Ivoire was compared between 126 patients who had received ART after 1998, and 166 patients with CD4 <200 who had received cotrimoxazole and were followed between 1996 and 1998. The ART group composed of 81% women, had a baseline median CD4 count of 137 cell/mm3 and were followed for a mean time of 21 months. The non-ART group was composed of 60% women, had a baseline median CD4 count of 100 cell/mm3 and was followed for a mean time of 16 months. The most frequent causes of severe illness in the groups were acute unexplained fever (ART vs. non-ART, per 100 patient years): 12.2 vs. 9.1, severe bacterial diseases: 9.2 vs. 25, non-specific enteritis: 9.1 vs. 23 and tuberculosis: 2.4 vs. 6.9. The incidence of malaria was the same in both groups (2.4 per 100 py).
References
Durier N, Treatment of HIV disease with HAART in Chiradzulu District, Malawi. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 112.
Ekong E, The Nigerian accelerated antiretroviral drug initiative – evaluation of nevirapine, lamivudine and stavudine in ARV naive patients. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 629.
Azondekon A, HAART in Benin initiative: what have been used and for whom? Lessons from 448 patients elected one year later. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 636.
Gahimbaza L. Costs and benefits of the antiretroviral therapy in the private sector: the experience of Brarudi, Burundi. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 668.
Mougnutou R, Evaluation of a HAART pilot study in Yaounde, Cameroon: 24 months follow-up. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 686.
Oyugi JH. Self-reported adherence measures are feasible and valid compared to multiple objective measures in kampala, Uganda. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 690.
Kebba A. Therapeutic responses to AZT+3TC+EFV in advanced ARV-naive HIV-1 infected Ugandans. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 693.
Idigbe EO. The use of generic copies of ARVs in the management of HIV infections in Lagos, Nigeria: a 6 month follwo-up study. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 697.
Kibangou N. Pointe-Noire, Congo-Brazzaville: ARV therapy assessment, an evaluation following 6 months of prescription. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 700.
Boulle A. Early outcomes and lessons from a public sector ARV treatment programme in South Africa. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 701.
Diop K. Adherence to ART in Senegal: assessment at the pharmacy level. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 705.
Laniece I. Determinants of adherence among adults receiving ARV drugs in Senegal (ANRS cohort study). IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 1118.
Nwokikr JI. Baseline data and predictors of adherence to ART in Maun General Hospital, Maun, Botswana. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 759.
Ndwapi N. Preliminary analysis of mortality and causes of death among the first ARV-treatment naive HIV-1C-infected persons receiving HAART under the Botswana national ARV treatment program. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 1212.
Wester W. Preliminary analysis of toxicity and tolerability among the first ARV-treatment naive HIV-1C-infected persons receiving HAART under the Botswana national ARV treatment program. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 1213.
Ndwapi N. Response to the Botswana national ART program - preliminary analysis of the first 306 treatment -naive adults receiving HAART via the national program. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 1216.
Seyler C. Morbidity causes in HIV-infected adults before and after the ART era in Abidjan, Cote d’Ivoire: Data from the Cotrame ANRS 1203 cohort study. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. LB53.
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