Antiretroviral (ARV) drug resistance in the developing world.

ABSTRACT To describe the overall prevalence of ARV resistance in the developing world, focusing on: (1) treatment naïve populations, (2) the resistance consequences of prevention of mother to child transmission (pMTCT) drug regimens, and (3) the relationship of medication adherence to resistance.
We searched PubMed(R), EMBASE, the Cochrane Controlled Clinical Trials Register Database, and the Cochrane Database of Reviews of Effectiveness (DARE). Additional sources of evidence included the Stanford University HIV Drug Resistance Database; reports of WATCH: Worldwide Analysis of Resistance Transmission over Time of Chronically and Acute Infected HIV-1 infected persons; a recent unpublished pMTCT overview; and various conference proceedings. Studies that did not report original research, that reported data already reported in another article, and case studies of fewer than 20 individuals were excluded. Of 1,122 titles identified, 117 journal articles and presentations were included.
We abstracted data on geographic region, number of participants, subject demographics, HIV viral clade, medications taken (if any), years of data collection, how people were selected for resistance testing, and how and when resistance was assessed. Because of study heterogeneity, pooling was not possible; thus, the data are summarized qualitatively. Differences by region, population group, and HIV viral clade are described.
The patterns of ARV resistance among treatment naïve populations worldwide appear to reflect geographic trends in use of ARV medications. A worldwide surveillance program (WATCH) found the rate of resistance (to any drug) among treatment naïve individuals was 5.5 percent in Africa, 7.4 percent in East Asia, 5.7 percent in Southeast Asia, and 6.4 percent in Latin America, lower than in North America (11.4 percent) and Europe (10.6 percent). Resistance data on HIV clades other than A, B, C, and D were too scarce to permit reliable conclusions. We also identified very few studies designed to assess the effect of health services delivery factors or medication adherence on the development of resistance in patients in developing countries. Evidence provided by longitudinal analyses suggests that, among women taking intrapartum single dose nevirapine (SD-NVP) to prevent mother-to-child transmission of HIV, both the overall prevalence of NNRTI resistance as well as the frequency of mutant virus in the overall viral population decreases with time since SD-NVP prophylaxis was received.
In future resistance studies, rare HIV clades should be over-sampled in order to provide statistically meaningful data. Resistance surveillance programs should be maintained throughout the developing world, and data should be reported and analyzed in a consistent and timely manner. Where resources permit, studies of adherence in developing regions should conduct resistance testing.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Sustainable interventions are needed to minimize HIV risk behavior among people living with HIV (PLWH) in South Africa on antiretroviral therapy (ART), a significant proportion of whom do not achieve viral suppression.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 09/2014; DOI:10.1097/QAI.0000000000000348 · 4.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human African trypanosomiasis or 'sleeping sickness' is a neglected tropical disease caused by the parasite Trypanosoma brucei. A decade of intense international cooperation has brought the incidence to fewer than 10,000 reported cases per annum with anti-trypanosomal drugs, particularly against stage 2 disease where the CNS is involved, being central to control. Treatment failures with melarsoprol started to appear in the 1990s and their incidence has risen sharply in many foci. Loss of plasma membrane transporters involved in drug uptake, particularly the P2 aminopurine transporter and also a transporter termed the high affinity pentamidine transporter, relate to melarsoprol resistance selected in the laboratory. The same two transporters are also responsible for the uptake of the stage 1 drug pentamidine and, to varying extents, other diamidines. However, reports of treatment failures with pentamidine have been rare from the field. Eflornithine (difluoromethylornithine) has replaced melarsoprol as first-line treatment in many regions. However, a need for protracted and complicated drug dosing regimens slowed widespread implementation of eflornithine monotherapy. A combination of eflornithine with nifurtimox substantially decreases the required dose and duration of eflornithine administration and this nifurtimox-eflornithine combination therapy has enjoyed rapid implementation. Unfortunately, selection of resistance to eflornithine in the laboratory is relatively easy (through loss of an amino acid transporter believed to be involved in its uptake), as is selection of resistance to nifurtimox. The first anecdotal reports of treatment failures with eflornithine monotherapy are emerging from some foci. The possibility that parasites resistant to melarsoprol on the one hand, and eflornithine on the other, are present in the field indicates that genes capable of conferring drug resistance to both drugs are in circulation. If new drugs, that act in ways that will not render them susceptible to resistance mechanisms already in circulation do not appear soon, there is also a risk that the current downward trend in Human African trypanosomiasis prevalence will be reversed and, as has happened in the past, the disease will become resurgent, only this time in a form that resists available drugs.
    Future Microbiology 09/2011; 6(9):1037-47. DOI:10.2217/fmb.11.88 · 3.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Considering that antibiotics play a crucial role in reducing morbidity and mortality due to bacterial infections, antibiotic resistance is a major problem in resource-limited countries (RLCs) where there is a high burden of infectious diseases, resistance rates are even higher than in industrialized countries, and therapeutical options are often unavailable or too expensive. Multidrug-resistant organisms – e.g. Streptococcus pneumoniae, Salmonella Typhi, Shigella spp., Neisseria gonorrhoeae, Mycobacterium tuberculosis – have been increasingly documented. Many factors contributing to antibiotic resistance in RLCs are strongly related to poverty: lack of knowledge or information of health-care professionals, lack of laboratory facilities, inadequate access to health system, lack of money available to pay for the appropriate amount of antibiotics, dispensation of drugs by untrained people, availability of substandard and counterfeit drugs, etc. Moreover, in RLCs, transmission of resistant bacteria is facilitated by person-to-person contact, through contaminated food, unsafe water or by vectors. An understanding of this complex and multifactorial scenario is crucial to develop any containment strategy based on the promotion of a correct use of antibiotics and infection control measures.
    12/2009: pages 199-231;