Potential market size and impact of hepatitis C treatment in low- and middle-income countries.

The introduction of direct-acting antiviral agents (DAAs) has made hepatitis C infection curable in the vast majority of cases and the elimination of the infection possible. Although initially too costly for large-scale use, recent reductions in DAA prices in some low- and middle-income countries (LaMICs) has improved the prospect of many people having access to these drugs/medications in the future. This article assesses the pricing and financing conditions under which the uptake of DAAs can increase to the point where the elimination of the disease in LaMICs is feasible. A Markov simulation model is used to study the dynamics of the infection with the introduction of treatment over a 10-year period. The impact on HCV-related mortality and HCV incidence is assessed under different financing scenarios assuming that the cost of the drugs is completely paid for out-of-pocket or reduced through either subsidy or drug price decreases. It is also assessed under different diagnostic and service delivery capacity scenarios separately for low-income (LIC), lower-middle-income (LMIC) and upper-middle-income countries (UMIC). Monte Carlo simulations are used for sensitivity analyses. At a price of US$ 1680 per 12-week treatment duration (based on negotiated Egyptian prices for an all oral two-DAA regimen), most of the people infected in LICs and LMICs would have limited access to treatment without subsidy or significant drug price decreases. However, people in UMICs would be able to access it even in the absence of a subsidy. For HCV treatment to have a significant impact on mortality and incidence, a significant scaling-up of diagnostic and service delivery capacity for HCV infection is needed.

Update on World Health Organization HIV drug resistance prevention and assessment strategy: 2004-2011.

The HIV drug resistance (HIVDR) prevention and assessment strategy, developed by the World Health Organization (WHO) in partnership with HIVResNet, includes monitoring of HIVDR early warning indicators, surveys to assess acquired and transmitted HIVDR, and development of an accredited HIVDR genotyping laboratory network to support survey implementation in resource-limited settings. As of June 2011, 52 countries had implemented at least 1 element of the strategy, and 27 laboratories had been accredited. As access to antiretrovirals expands under the WHO/Joint United Nations Programme on HIV/AIDS Treatment 2.0 initiative, it is essential to strengthen HIVDR surveillance efforts in the face of increasing concern about HIVDR emergence and transmission.

Preventive therapy for tuberculosis in HIV infection: the promise and the reality.

PIP: An increasing incidence of tuberculosis has been recorded in areas where both human immunodeficiency virus (HIV) and Mycobacterium tuberculosis are prevalent. 98% of HIV-associated tuberculosis cases occur in developing countries, most notably sub-Saharan Africa. This trend has led to the consideration of tuberculosis prevention therapy for HIV-infected patients. The efficacy of isoniazid for this purpose has been demonstrated in numerous clinical trials, but its application has been limited by concerns about hepatotoxicity, non-adherence, drug resistance, and costs. Recommended is the approach adopted in the US of providing a six-month course of isoniazid to those with a positive tuberculin skin test reaction and epidemiologic risk factors; for those already infected with HIV, 12 months of treatment is suggested. Rifampicin preventive therapy is recommended for those infected by isoniazid-resistant bacilli. Needed are studies to assess operational feasibility, cost-benefits, the use of life-long isoniazid preventive therapy in areas of high tuberculosis transmission, and alternative regimens such as short-course multidrug treatment.^ieng

Treatment, prophylaxis and research priorities for developing countries.

PIP: An estimated two million new adult and pediatric HIV infections occurred worldwide during 1992, more than 50% of them in sub-Saharan Africa, 25% in Asia, and one-eighth in Latin America and the Caribbean. The remaining infections occurred in Europe, North America, and the industrialized countries of the Pacific Rim. Transmission by sexual intercourse and from an infected woman to her fetus/child remain major routes of transmission. The World Health Organization estimates that there will be a cumulative total of 30-40 million people infected with HIV by the year 2000. Over time, increasing numbers of people already infected with HIV and soon to be infected will develop AIDS and require higher levels of care. Obstacles to increasing access to cost-effective drugs for HIV/AIDS in developing countries, however, include weak drug distribution systems, the improper prescribing of available drugs by health workers, and the improper use of these drugs by patients who have not been appropriately educated by prescribing health workers. Currency shortages and lack of political will underlie these obstacles. This paper considers cost-effective prophylaxis and treatment of HIV-related infections including tuberculosis, candidiasis, penicilliosis, combined chemoprophylaxis, pruritus and diarrhea with wasting, and HIV infection. The prevention of HIV transmission is discussed under headings on heterosexual and perinatal transmission, followed by a discussion on increasing access to cost-effective drugs.^ieng

Safety of multiple daily applications of COL-1492, a nonoxynol-9 vaginal gel, among female sex workers. COL-1492 Phase II Study Group.

RATIONALE: COL-1492 is a nonoxynol-9 (N-9)-containing vaginal gel and may be a potential microbicide. As part of an effectiveness trial, an initial toxicity study was conducted. OBJECTIVES: The main objective of the reported study was the assessment of the toxicity of a 52.5 mg N-9 gel, COL-1492, when used a number of times each day by female sex workers. METHODS: This was a randomized, placebo-controlled triple-blinded trial among female sex workers. The participants were asked to use the product for each vaginal sexual act. At each monthly visit a gynaecological examination with sexually transmitted disease sampling and colposcopy was performed. Venous blood was drawn for syphilis and HIV serology. All women received intensive counselling on condom use. Male condoms and sexually transmitted disease treatment were given free of charge. RESULTS: Only blinded results on the colposcopic examinations are reported. The incidence of lesions with or without an epithelial disruption was low: 0.06 and 0.29, respectively, per 100 woman-days in group A; 0.09 and 0.26 respectively per 100 woman-days in group B. There was no significant difference between the two arms. CONCLUSION: The multiple daily use of COL-1492 by female sex workers did not show an increase of local toxicity over that of a placebo. Colposcopy was discontinued in the autumn of 1997 in accordance with a Data Safety Monitoring Board decision. In the currently ongoing effectiveness trial the assessment of the product's toxicity continues to be monitored by simple visual examination.

An analysis of the economic impact of HIV infection among patients at Mama Yemo Hospital, Kinshasa, Zaire.

In a prospective study of adult admissions to the Department of Internal Medicine at Mama Yemo Hospital, Kinshasa, Zaire in late 1988, 129 women and 122 men were screened for HIV infection. Fifty per cent were found to be seropositive, with half of the seropositives meeting the World Health Organization (WHO) clinical AIDS definition. The HIV seropositives had a mortality rate of 50%, which was significantly higher (P = 0.004) than the 30% mortality rate seen in the seronegative group. Direct costs during hospitalization did not differ ($60.30 for HIV seropositives, $56.50 for HIV seronegatives), but pre-hospitalization expenses were significantly higher in the HIV-seropositive group ($170 for HIV seropositives, $110 for HIV seronegatives). Years of productive life lost due to death were also significantly higher for HIV seropositives versus HIV seronegatives (30.6 versus 21.3 years; P = 0.0007), and 73% of the premature mortality in the study population was attributable to HIV infection.

Anti-A60 immunoglobulin G in the serodiagnosis of tuberculosis in HIV-seropositive and seronegative patients.

OBJECTIVE: A60 is a high molecular weight mycobacterial antigen complex. The detection of immunoglobulin (Ig) G antibodies to A60 has been advocated as a reasonably sensitive and specific test for active tuberculosis (TB). We aimed to compare the sensitivity of this test among HIV-seropositive and HIV-seronegative patients with pulmonary TB. METHODS: The presence and concentration of anti-A60 IgG antibodies was assessed by enzyme-linked immunosorbent assay in 208 HIV-seropositive and 91 HIV-seronegative Zaïrian patients with smear-positive pulmonary TB. The relationship between anti-A60 IgG levels and HIV serostatus, CD4+ lymphocyte counts, presence of clinical AIDS, and tuberculin skin test results was verified. RESULTS: Only 36.5% of the HIV-seropositive, compared with 69.2% of the HIV-seronegative patients had a positive anti-A60 IgG test (P < 0.00001). Among HIV-seropositive patients, anti-A60 IgG levels did not differ according to CD4+ lymphocyte counts, presence of clinical AIDS, or tuberculin skin test results. CONCLUSIONS: Among patients with pulmonary TB, the sensitivity of testing for anti-A60 IgG was much lower among HIV-seropositive than among HIV-seronegative patients, even from the early stages of HIV-related immunodeficiency. This limits the utility of anti-A60 IgG-antibody testing in the diagnosis of TB among HIV-infected patients.

Prevention of blood-borne HIV transmission using a decentralized approach in Shaba, Zaire.

OBJECTIVE: To prevent blood transfusion-acquired HIV infection with a decentralized approach to HIV screening of blood donors, using an instrument-free rapid test. SETTING: Shaba province, Zaire (496,877 km2). METHODS: The programme consisted of training health-care workers, distribution of a rapid HIV-antibody test (DuPont's HIVCHEK) for screening of all blood donations, and quality control of testing by a regional reference centre. RESULTS: Over a 2-year period, 11,940 rapid tests were distributed to 37 hospitals, covering 75% of all hospital beds outside the copper mine's health system in Shaba. Eighty-five per cent of the tests were used to screen blood donors (5.4% positive test rate) and 13% to test patients (39.7% positive test rate). At least 265 cases of HIV-positive blood donation were prevented, at an estimated cost of 137-279 ECU per case. Only 26% of initially positive specimens reached the central laboratory for supplemental testing, and sterile transfusion equipment and blood-grouping reagents were frequently unavailable. The lack of transport and communications and a deteriorating health system were major constraints. CONCLUSIONS: District hospitals in Africa are often long distances from major cities, difficult to reach for most of the year, and perform a small number of transfusions. In this context a classical centralized regional blood bank may not be a feasible option to ensure safe blood transfusions. However, safe blood transfusion can be achieved with a decentralized approach using a rapid test, provided that minimum standards of health-care services are available.

PIP: This program aimed at preventing blood transfusion-acquired HIV infection with a decentralized approach to HIV screening of blood donors using an instrument free raid test was initiated in Shaba province in Zaire (496,877 sq. km and included training of health care workers, distribution of a rapid HIV-antibody test (DuPont's HIVCHEK) for screening of all blood donations, and quality control of testing by a regional reference center. Over a 2-year period, 11,940 rapid tests were distributed to 37 hospitals, covering 75% of all hospital beds outside the copper mine's health system in Shaba. 85% of the tests were used to screen blood donors (5.4% positive test rate) and 13% to test patients (39.7% positive test rate). At least 265 cases of HIV-positive blood donation were prevented at an estimated cost of 137-279 ECU per case. Only 26% of initially positive specimens reached the central laboratory for supplemental testing, and sterile transfusion equipment and blood-grouping reagents were frequently unavailable. The lack of transport and communications and a deteriorating health system were major constraints. District hospitals in Africa are often long distances from major cities, difficult to reach for most of the year, and perform a small number of transfusions. In this context, a classical centralized regional blood bank may not be a feasible option to ensure safe blood transfusions. However, safe blood transfusion can be achieved with a decentralized approach using a rapid test, provided that minimum standards of health care services, are available.

A clinical and pathological comparison of the WHO and CDC case definitions for AIDS in Kinshasa, Zaïre: is passive surveillance valid?

OBJECTIVES: To compare the specificity of the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) case definitions for AIDS in autopsy cases from Zaïre. SETTING: Mama Yemo Hospital and University Hospital morgues in Kinshasa, and Karawa Hospital in Equateur Region, Zaïre. METHODS: Autopsy cases with a clinical diagnosis of AIDS on the death certificate or chart were studied. Evaluation included post-mortem HIV-1 serology, chart review for specific AIDS-related symptoms and signs, and application of WHO and CDC case criteria to the clinical and autopsy diagnoses. RESULTS: Of the 68 diagnosed AIDS cases, 98% fulfilled WHO criteria for AIDS and 93% fulfilled both WHO and CDC criteria. All cases fulfilling both criteria were HIV-1-seropositive. Opportunistic infections accounted for 84% of CDC AIDS-defining conditions. Disseminated tuberculosis was the most frequent (41%) specific diagnosis; Pneumocystis carinii pneumonia was rare (< 2%). CONCLUSIONS: There was good concordance between WHO and CDC case definitions. A diagnosis of AIDS on the chart or death certificate is adequate for surveillance purposes in this population.

Safety evaluation of nonoxynol-9 gel in women at low risk of HIV infection.

OBJECTIVE: To determine the safety of a vaginal microbicide, COL-1492, containing 52.5 mg nonoxynol-9, applied once daily for 14 days among healthy volunteers. METHODS: A randomized, double-blind controlled trial with three arms, COL-1492 gel versus placebo gel versus no-treatment controls, was conducted. Outcomes of interest were reported genital symptoms, incidence of gynaecological signs, and incidence of genital lesions revealed by colposcopy. Participants were enrolled in four centres (Belgium, The Netherlands, and two in Thailand). RESULTS: A total of 534 women participated in the study: 179 used COL-1492, 178 used placebo, and 177 were no-treatment controls. Study visits were scheduled 1 week prior to enrollment (day -7), day 0 (enrollment), day 8 and day 14. The most frequently reported genital symptom was vaginal discharge in both the COL-1492 and placebo groups. This appeared to be related to leakage of the product out of the vagina. The incidence of lesions associated with epithelial disruption (ulcers and abrasions) was very low (< 2%) and there was no statistically significant difference between the three groups. Of the lesions observed by colposcopy that did not involve epithelial disruption, petechial haemorrhage was the most frequently detected, with an incidence of 20.1, 9.0 and 7.3% in the COL-1492, placebo and control groups, respectively. COL-1492 users had a higher incidence of erythema (8.4 versus 2% in the other groups). CONCLUSION: COL-1492 showed minimal toxicity when applied once daily. A Phase III trial to assess the product's effectiveness in HIV prevention is currently ongoing.

Prevention of transfusion-associated HIV transmission in Kinshasa, Zaire: HIV screening is not enough.

The purpose of this study was to develop a strategy to reduce transfusion-related HIV transmission which went beyond the limits of routine HIV screening of blood donors. Current blood transfusion practices were assessed in 1044 patients for whom staff physicians had requested a transfusion between 5 September and 19 October, 1988. Children under 5 years of age with malaria, and pregnant women with acute anaemia requiring blood transfusion were the two highest risk groups. Many of the transfusions were given without an obvious medical indication; 22.7% (214 out of 955) of the recipients were transfused without prior laboratory tests [haemoglobin (Hb) or haematocrit (Hct)], 7.2% with Hb greater than 6g/100ml or Hct greater than 25% and 16.6% without clinical signs of severe anaemia (pulse less than 100/min without shortness of breath). The data of this study were used to organize a workshop for all the physicians responsible for blood transfusions in Kinshasa and two nearby health zones. A consensus statement on the indications for blood transfusion was developed. Subsequently, transfusion centres adopted this consensus statement instead of previous guidelines.

Low and stable HIV seroprevalence in pregnant women in Shaba province, Zaire.

Sentinel serosurveillance for HIV infection has been carried out in Shaba province, Zaire, among consecutive pregnant women attending antenatal clinics from 1989 to 1991. There were four surveillance sites (three urban and one semiurban), at which a total of 13 surveillance studies were made of 4,205 women. Overall, 3.1% were HIV seropositive. There were no significant differences in HIV seroprevalence between surveillance sites, and HIV seroprevalence did not increase at any of the surveillance sites during the 2-year period of study. Since changes in the population studied did not occur between surveillance studies, it is believed that the observed stable trend reflects stable HIV seroprevalence rates in the general adult population of the surveillance sites. Collateral HIV seroprevalence data were available from 8,725 blood donors at 20 sites (six urban, 14 rural) in the province, who had an overall HIV seroprevalence of 4.6%. The higher HIV seroprevalence rate among blood donors was probably due to selection bias, since HIV seroprevalence rates in two blood banks, which relied nearly exclusively on replacement donors, were 2.7 and 2.8%, our best estimate for HIV seroprevalence in the three cities where blood banks exist and where no surveillance studies were carried out. The stable and relatively low HIV seroprevalence rates in Shaba province are in sharp contrast with the rapidly increasing and much higher rates in neighboring Zambia and other East African cities. Reasons for this discrepancy are unclear, and their eludication may yield critical information for HIV prevention programs.

Neurological complications of HIV-1-seropositive internal medicine inpatients in Kinshasa, Zaire.

Because little was known about the prevalence of neurological complications of human immunodeficiency virus type 1 (HIV-1) infection in Africa, we conducted a cross-sectional study among consecutive admissions to the internal medicine wards of Mama Yemo Hospital in Kinshasa, Zaire. Of the 196 patients studied, 104 (53%) were HIV-1 seropositive, of whom 50 (48%) had stage 3 and 49 (47%) had stage 4 HIV-1 infection according to the provisional WHO staging criteria for HIV infection. Neuropsychiatric abnormalities were present in 43 (41%) of 104 HIV-1-seropositive patients. Of the HIV-1-seropositive patients, 9 (8.7%; 95% confidence interval, 4-16%) were diagnosed as having possible HIV-1-associated dementia complex, 1 (1%) as having possible HIV-1 myelopathy, and 3 (2.7%) as having possible HIV-1-associated minor cognitive/motor disorder. Definitive diagnoses could not be made because there were no facilities for neuroimaging and neuropathology. Meningitis caused by cryptococcus was diagnosed in six (5.6%) and by Mycobacterium avium in two (2%) of the HIV-1 seropositive patients. Acute onset hemiplegia, believed to be due to stroke, was present in four (4%) of the HIV-1-seropositive patients. The prevalence of other central nervous system opportunistic infections and mass lesions, especially toxoplasmic encephalitis, could not be assessed. In this population of Zairian inpatients, the prevalence of neurological complications of HIV-1 infection was similar to that observed in industrialized countries among patients with advanced HIV disease.

Use of a rapid test and an ELISA for HIV antibody screening of pooled serum samples in Lubumbashi, Zaire.

Pools with a size of 3 and 5 were prepared by mixing one HIV confirmed HIV-1 seropositive serum with either 2 or 4 HIV seronegative sera at the Regional HIV Laboratory in Lubumbashi, Zaire. These pools were assessed in a blind fashion by ELISA (Vironostika anti-HTLV-III microELISA system, Organon Technika). Similarly constituted pools of 3 samples were assayed by a rapid test with visual reading (HIVCHEK 1 + 2, Dupont de Nemours). With the HIVCHEK, pooling was achieved on the test device itself by dropping consecutively 3 different serum samples on the devices's membrane. After the last serum was soaked in, wash fluid and conjugate were added. Results of the pooling experiments were compared with testing sera individually. The ELISA results from pools and from individual tested samples matched completely if, and only if, the final dilution of individual samples in the reagent medium was the same as recommended by the manufacturer for testing of individual samples. With the HIVCHEK a sensitivity of 99-100% was obtained with pooled sera. Both approaches seemed sensitive enough to enable their use for screening of blood donors and patient management, but a prospective study to validate these preliminary results is necessary.

Prevalence of enteric viruses among hospital patients with AIDS in Kinshasa, Zaire.

Diarrhoea is the most common manifestation of acquired immunodeficiency syndrome (AIDS) in Africa. Numerous parasitic or bacterial agents have been implicated, but a pathogen-specific aetiology has not been found. Enteric viruses (i.e., rotavirus, small round structured viruses, coronavirus, and adenovirus) were detected by enzyme-linked immunosorbent assay or electron microscopy in faecal specimens of 17% of 198 consecutive adult admissions to a general medical ward of an urban hospital in Kinshasa, Zaire. Overall, 57% of patients were seropositive for infection with human immunodeficiency virus (HIV) 1; of these, 50% were classified as World Health Organization AIDS stage IV. The prevalence of enteric viruses in stool specimens did not differ significantly between patients with and without HIV infection, and was not associated with acute or chronic diarrhoea, or constitutional symptoms. However, a trend (P = 0.14) towards greater frequency of virus in stools from patients in the lower 3 quintiles of the CD4/CD8 T cell ratio was seen. This trend approached statistical significance (P = 0.07) with stratification by HIV infection. Although we found no evidence in this population to support a major pathogenic role for these viruses alone in the enteropathy of AIDS, increased viral shedding was weakly associated with immunodeficiency.

PIP: During July-October 1989 in Zaire, a physician examined and took blood and stool samples from 198 adult patients at Mama Yemo Hospital in central Kinshasa to learn the prevalence of enteric viruses and their link to diarrhea, immunosuppression, and wasting among HIV infected and uninfected patients. In Kinshasa, diarrhea is prevalent and heterosexual intercourse is the main mode of HIV transmission. 57.6% of the patients were infected with HIV. 50% of the HIV-positive patients had AIDS. 93% of all HIV-positive patients either had AIDS (stage IV) or advanced stage III disease. 49% of them died while in the hospital. 22% of the HIV-negative patients died while in the hospital. 17% of all adult patients studied were infected with at least 1 enteric virus, especially rotavirus. Enteric viruses were isolated from both HIV infected and uninfected patients (17% and 18%, respectively). State of immunocompromise did not significantly affect viral shedding, but fewer patients in the less immunocompromised stages shed viruses than did those in the advanced stages of immunocompromise (3 vs. 72 patients). When examining the ratio of circulating CD4 and CD8 T cells in HIV-infected patients, however, there was a trend toward greater frequency of enteric viruses (p = .07). Chronic diarrhea was significantly associated with HIV seropositivity (p 0.01), HIV stage (p .001), and CD4/CD8 T cell ratio (p .01). Acute diarrhea was not associated with any of the above, however. These findings suggest that enteric viruses were not a significant cause of diarrhea, but they were isolated somewhat more often in patients of advanced immunosuppression.

Incidence of malaria and efficacy of oral quinine in patients recently infected with human immunodeficiency virus in Kinshasa, Zaire.

There is concern that the impaired cell mediated immunity caused by the human immunodeficiency virus may increase the risk of severity of Plasmodium falciparum infection and could lead eventually to a decreased response to standard antimalarial treatment. In 1986, at Mama Yemo Hospital, Kinshasa, Zaire, the incidence of malaria was determined in a cohort of 59 patients who had recently acquired HIV-I infection through blood transfusion and in a cohort of 83 HIV-I seronegative controls who were recipients of HIV-I seronegative blood. All cohort patients were asked to visit the study physician whenever they developed fever. On each of these occasions thick film was examined for the presence of malarial parasites. HIV-I seropositive patients presented more often with episodes of fever per person month observation than HIV-I seronegative patients (P = 0.003). The total number of positive thick films per person months observation was significantly higher among HIV-I seropositive patients than among the HIV-I seronegative ones, but percentages of positive thick films per episode of fever were the same in both groups (46%). During a 5 month period, cohort patients presenting with a moderate attack of malaria were treated with oral quinine 20 mg/kg daily in two doses for 5 days. Twenty-three (92%) of 25 HIV-I seropositive patients and 28 (82%) of 34 HIV-I seronegative patients had a negative film 7 days after starting treatment. This study suggests that there seems to be no direct interaction of major clinical importance between HIV infection and malaria.

High-dose cyclophosphamide and dexamethasone in paraquat poisoning: a prospective study.

Between March 1986 and March 1988, 47 consecutive patients, whose paraquat intoxication was confirmed by urine testing, were enrolled in a prospective study on the treatment of paraquat poisoning. Fourteen received a standard treatment regimen consisting of fluid replacement and oral absorbents, and 33 received high-dose cyclophosphamide and dexamethasone, in addition to standard therapy. The case fatality rate in both treatment groups (63 and 61%) was similar. In addition, all 26 patients whose paraquat serum concentrations were measured and who had a probability of survival of less than 65% according the survival curve of Hart et al. died, regardless of therapy. These included four in the cyclophosphamide/dexamethasone group and two in the standard treatment group who had prior survival probabilities between 50 and 65%. This indicated that the cut-off curve relating mortality and paraquat serum concentrations was similar in both treatment groups. High-dose cyclophosphamide/dexamethasone treatment is unlikely to improve the prognosis of paraquat poisoning.

Caring for patients with HIV and AIDS in middle income countries.

PIP: Increased access, in middle-income countries, to innovative but costly medical technologies for the treatment of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) raises important policy considerations about how to optimize their use. Realizing the full potential of antiretroviral therapy, for example, requires widespread availability of HIV tests to identify those in the early stage of HIV infection, counseling services to inform people of their test results and explain the therapeutic options, available and affordable drugs, monitoring of drug efficacy and toxicity, mechanisms to ensure long-term compliance, and well functioning psychosocial support systems. In Thailand, a cost-effectiveness study modelling the use of different antiretroviral treatment options demonstrated that investments in antiretroviral therapy and formula feeding to prevent maternal-child HIV transmission were more effective and affordable than providing antiretroviral agents to those with established HIV infection. The cost of preventing vertical HIV transmission amounted to 16% of Thailand's national AIDS budget. The cost of extending access to and compliance with treatment and preventing opportunistic infections would be 129% of the budget, while that of providing antiretroviral drugs to all those with symptomatic HIV infection would be 235-630% of the budget (depending on the complexity of the regimen). More such studies are needed to develop a conceptual framework for policy development.^ieng